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1
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Shi J, Peng B, Xu R, Chang X, Wang C, Zhou X, Zhang L. Exploration oxidative stress underlying gastroesophageal reflux disease and therapeutic targets identification: a multi-omics Mendelian randomization study. Postgrad Med J 2024:qgae182. [PMID: 39671389 DOI: 10.1093/postmj/qgae182] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/20/2024] [Revised: 10/12/2024] [Accepted: 12/06/2024] [Indexed: 12/15/2024]
Abstract
INTRODUCTION Gastroesophageal reflux disease (GERD) is a chronic inflammatory gastrointestinal disease, which has no thoroughly effective or safe treatment. Elevated oxidative stress is a common consequence of chronic inflammatory conditions. METHODS We employed Summary-data based MR (SMR) analysis to assess the associations between gene molecular characteristics and GERD. Exposure data were the summary-level data on the levels of DNA methylation, gene expression, and protein expression, which obtained from related methylation, expression, and protein quantitative trait loci investigations (mQTL, eQTL, and pQTL). Outcome data, Genome-wide association study (GWAS) summary statistics of GERD, were extracted from the Ong's study (discovery), the Dönertaş's study (replication), and the FinnGen study (replication). Colocalization analysis was performed to determine if the detected signal pairs shared a causative genetic mutation. Oxidative stress related genes and druggable genes were imported to explore oxidative stress mechanism underlying GERD and therapeutic targets of GERD. The Drugbank database was utilized to conduct druggability evaluation. RESULTS After multi-omics SMR analysis and colocalization analysis, we identified seven key genes for GERD, which were SUOX and SERPING1, DUSP13, SULT1A1, LMOD1, UBE2L6, and PSCA. SUOX was screened out to be the mediator, which suggest that GERD is related to oxidative stress. SERPING1, SULT1A1, and PSCA were selected to be the druggable genes. CONCLUSIONS These findings offered strong support for the identification of GERD treatment targets in the future as well as for the study of the oxidative stress mechanism underlying GERD.
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Affiliation(s)
- Jiaxin Shi
- Department of Thoracic Surgery, The Second Affiliated Hospital of Harbin Medical University, 246 Xuefu Road, Nangang District, Harbin 150081, China
| | - Bo Peng
- Department of Thoracic Surgery, The Second Affiliated Hospital of Harbin Medical University, 246 Xuefu Road, Nangang District, Harbin 150081, China
| | - Ran Xu
- Department of Thoracic Surgery, The Second Affiliated Hospital of Harbin Medical University, 246 Xuefu Road, Nangang District, Harbin 150081, China
| | - Xiaoyan Chang
- Department of Thoracic Surgery, The Second Affiliated Hospital of Harbin Medical University, 246 Xuefu Road, Nangang District, Harbin 150081, China
| | - Chenghao Wang
- Department of Thoracic Surgery, The Second Affiliated Hospital of Harbin Medical University, 246 Xuefu Road, Nangang District, Harbin 150081, China
| | - Xiang Zhou
- Department of Thoracic Surgery, The Second Affiliated Hospital of Harbin Medical University, 246 Xuefu Road, Nangang District, Harbin 150081, China
| | - Linyou Zhang
- Department of Thoracic Surgery, The Second Affiliated Hospital of Harbin Medical University, 246 Xuefu Road, Nangang District, Harbin 150081, China
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Babu G, Bin Islam S, Khan MA. A review on the genetic polymorphisms and susceptibility of cancer patients in Bangladesh. Mol Biol Rep 2022; 49:6725-6739. [PMID: 35277785 DOI: 10.1007/s11033-022-07282-8] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/06/2021] [Revised: 02/14/2022] [Accepted: 02/16/2022] [Indexed: 10/18/2022]
Abstract
Cancer is one of the major health burdens worldwide, and genetic polymorphisms in individuals are closely associated with cancer susceptibility. Like in many other developing countries, the risk of cancer is increasing among Bangladeshi population. Genetic polymorphisms in xenobiotic metabolic enzymes (CYP1A1, CYP2A6, CYP3A4, CYP3A5, NAT2, SULT1A), cell cycle regulatory proteins (TP53, HER2, MDM2, miR-218-2, TGFB), cell signaling protein (CDH1), DNA repair proteins (BRCA1, BRCA2, EXO1, RAD51, XRCC2, ECCR1, ERCC4, XPC, ERCC2), and others (HLA-DRB1, INSIG2, GCNT1P5) have been found to be associated with various cancers like cancers of breast, bladder, cervix, colon, lung, prostate, etc. in different studies with Bangladeshi population. In this review article, we have discussed these gene polymorphisms associated with cancers in the Bangladeshi population, and also made a comparison with other ethnic groups. This will probably be helpful in understanding drug effects, drug resistance, and personalized medicine in the population of this region.
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Affiliation(s)
- Golap Babu
- Department of Biochemistry and Molecular Biology, Jahangirnagar University, 1342, Dhaka, Bangladesh
| | - Shad Bin Islam
- Bachelor in Medicine and Surgery Program, Affiliated hospital of Southwest Medical University, Luzhou, Sichuan, China
| | - Md Asaduzzaman Khan
- Key Laboratory of Epigenetics and Oncology, The Research Center for Preclinical Medicine, Southwest Medical University, 646000, Luzhou, Sichuan, China.
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Screening Gene Expression-Related Alternative Splicing Event Signature for Colon Cancer Prognostic Prediction. JOURNAL OF ONCOLOGY 2022; 2022:9952438. [PMID: 35126520 PMCID: PMC8813276 DOI: 10.1155/2022/9952438] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 03/26/2021] [Revised: 09/24/2021] [Accepted: 12/18/2021] [Indexed: 12/09/2022]
Abstract
Colon cancer is a kind of common intestinal disease, and early diagnosis of colon cancer is crucial for patient's prognosis. RNA alternative splicing (AS) is an RNA modification that affects cancer occurrence. RNA AS detection is promising to improve the in-depth understanding of the pathological mechanisms in colon cancer. In this study, differential analysis was performed to determine colon cancer-related AS events and the corresponding parental genes. Subsequently, GO functional annotation analysis was carried out on the parental genes, which revealed that these AS events might affect cell adhesion and cell growth. Besides, protein-protein interaction (PPI) network was established with the parental genes, in which MCODE was utilized to identify major functional modules. Enrichment analysis for the major functional module was implemented again, which demonstrated that these genes were mainly concentrated in the ribosome, protein ubiquitination, cell adhesion molecule binding, and other relevant biological functions. Next, differentially expressed genes (DEGs) were screened from colon cancer and normal tissues and overlapped with the parental genes, by which 55 gene expression-associated AS and the corresponding 45 genes were obtained. Moreover, a correlation analysis between splicing factors (SFs) and AS was done to identify interactions. On this basis, an SF-AS network was constructed. The univariate Cox regression analysis was employed to screen prognostic AS signature and establish a risk model. To assess the model, K-M and ROC analyses were done for model assessment, indicating the effective prediction performance. Combined with common clinicopathological features, the multivariate Cox regression analysis was conducted to confirm whether the risk model could be considered as an independent prognostic indicator. Finally, the expression status of the parental genes for the prognostic AS was evaluated between normal and colon cancer cells using qRT-PCR. In summary, TCGA SpliceSeq data were comprehensively analyzed, and a 5-AS prognostic model was constructed for colon cancer.
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Kurogi K, Rasool MI, Alherz FA, El Daibani AA, Bairam AF, Abunnaja MS, Yasuda S, Wilson LJ, Hui Y, Liu MC. SULT genetic polymorphisms: physiological, pharmacological and clinical implications. Expert Opin Drug Metab Toxicol 2021; 17:767-784. [PMID: 34107842 DOI: 10.1080/17425255.2021.1940952] [Citation(s) in RCA: 24] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/21/2022]
Abstract
INTRODUCTION Cytosolic sulfotransferases (SULTs)-mediated sulfation is critically involved in the metabolism of key endogenous compounds, such as catecholamines and thyroid/steroid hormones, as well as a variety of drugs and other xenobiotics. Studies performed in the past three decades have yielded a good understanding about the enzymology of the SULTs and their structural biology, phylogenetic relationships, tissue/organ-specific/developmental expression, as well as the regulation of the SULT gene expression. An emerging area is related to the functional impact of the SULT genetic polymorphisms. AREAS COVERED The current review aims to summarize our current knowledge about the above-mentioned aspects of the SULT research. An emphasis is on the information concerning the effects of the polymorphisms of the SULT genes on the functional activity of the SULT allozymes and the associated physiological, pharmacological, and clinical implications. EXPERT OPINION Elucidation of how SULT SNPs may influence the drug-sulfating activity of SULT allozymes will help understand the differential drug metabolism and eventually aid in formulating personalized drug regimens. Moreover, the information concerning the differential sulfating activities of SULT allozymes toward endogenous compounds may allow for the development of strategies for mitigating anomalies in the metabolism of these endogenous compounds in individuals with certain SULT genotypes.
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Affiliation(s)
- Katsuhisa Kurogi
- Department of Pharmacology, College of Pharmacy and Pharmaceutical Sciences, University of Toledo Health Science Campus, Toledo, OH 43614 USA.,Department of Biochemistry and Applied Biosciences, University of Miyazaki, Miyazaki, 889-2192, Japan
| | - Mohammed I Rasool
- Department of Pharmacology, College of Pharmacy and Pharmaceutical Sciences, University of Toledo Health Science Campus, Toledo, OH 43614 USA.,Department of Pharmacology, College of Pharmacy, University of Karbala, Karbala, Iraq
| | - Fatemah A Alherz
- Department of Pharmacology, College of Pharmacy and Pharmaceutical Sciences, University of Toledo Health Science Campus, Toledo, OH 43614 USA.,Department of Pharmaceutical Sciences, College of Pharmacy, Princess Nourah Bint Abdulrahman University, Riyadh, Saudi Arabia
| | - Amal A El Daibani
- Department of Pharmacology, College of Pharmacy and Pharmaceutical Sciences, University of Toledo Health Science Campus, Toledo, OH 43614 USA
| | - Ahsan F Bairam
- Department of Pharmacology, College of Pharmacy and Pharmaceutical Sciences, University of Toledo Health Science Campus, Toledo, OH 43614 USA.,Department of Pharmacology, College of Pharmacy, University of Kufa, Najaf, Iraq
| | - Maryam S Abunnaja
- Department of Pharmacology, College of Pharmacy and Pharmaceutical Sciences, University of Toledo Health Science Campus, Toledo, OH 43614 USA
| | - Shin Yasuda
- Department of Pharmacology, College of Pharmacy and Pharmaceutical Sciences, University of Toledo Health Science Campus, Toledo, OH 43614 USA.,Department of Bioscience, School of Agriculture, Tokai University, Kumamoto City, Kumamoto 862-8652, Japan
| | - Lauren J Wilson
- Department of Pharmacology, College of Pharmacy and Pharmaceutical Sciences, University of Toledo Health Science Campus, Toledo, OH 43614 USA
| | - Ying Hui
- Department of Pharmacology, College of Pharmacy and Pharmaceutical Sciences, University of Toledo Health Science Campus, Toledo, OH 43614 USA.,Department of Obstetrics and Gynecology, Beijing Hospital, Beijing, China
| | - Ming-Cheh Liu
- Department of Pharmacology, College of Pharmacy and Pharmaceutical Sciences, University of Toledo Health Science Campus, Toledo, OH 43614 USA
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Abstract
Despite increased research, the risks of developing esophageal cancer and of death from this disease, especially among men, have increased worldwide. The goals of this review include an assessment of male predominance of esophageal cancer and an analysis of its high mortality rates. Determination of the genetic and environmental factors associated with esophageal cancer may help explain its male predominance and help design more effective treatments of this disease.
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Affiliation(s)
- Olivia Dix
- Internal Medicine, Xavier University School of Medicine, Oranjestad, ABW
| | - Mala Thakur
- Internal Medicine, Xavier University School of Medicine, Oranjestad, ABW
| | - Alessia Genova
- Internal Medicine, Xavier University School of Medicine, Oranjestad, ABW
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Aversa J, Song M, Shimazu T, Inoue M, Charvat H, Yamaji T, Sawada N, Pfeiffer RM, Karimi P, Dawsey SM, Rabkin CS, Tsugane S, Camargo MC. Prediagnostic circulating inflammation biomarkers and esophageal squamous cell carcinoma: A case-cohort study in Japan. Int J Cancer 2019; 147:686-691. [PMID: 31671219 DOI: 10.1002/ijc.32763] [Citation(s) in RCA: 26] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/31/2019] [Revised: 10/14/2019] [Accepted: 10/15/2019] [Indexed: 01/05/2023]
Abstract
Esophageal squamous cell carcinoma (ESCC) is the predominant histologic subtype of esophageal cancer worldwide. Measurements of circulating inflammation-related biomarkers may inform etiology or provide noninvasive signatures for early diagnosis. We therefore examined levels of inflammation molecules for associations with ESCC risk. Using a case-cohort study designed within the Japan Public Health Center-based Prospective Study, we measured baseline plasma levels of 92 biomarkers using a multiplex assay in a subcohort of 410 randomly selected participants and 66 participants with incident ESCC (including four cases that occurred in the subcohort). ESCC hazard ratios (HRs) were calculated for 2-4 quantiles of each biomarker by Cox proportional hazards regression models with age as the time metric, adjusted for sex, smoking and alcohol use. Twenty analytes were undetectable in nearly all samples. Of the remaining 72, 12 biomarkers (FGF19, ST1A1, STAMBP, AXIN1, CASP8, NT3, CD6, CDCP1, CD5, SLAMF1, OPG and CSF1) were associated with increased ESCC risk (ptrend < 0.05) with HRs per quantile 1.28-1.65. Seven biomarkers (CXCL6, CCL23, CXCL5, TGFA, CXCL1, OSM and CCL4) were inversely associated with HRs 0.57-0.72. FGF19, CASP8, STAMBP, ST1A1 and CCL-4 met statistical significance with false discovery rate correction. Associations did not differ <5 vs. ≥5 years between blood collection and ESCC diagnosis. CASP8, STAMBP and ST1A1 were strongly correlated (p < 0.05). Our study expands the range of inflammation molecules associated with the development of this highly lethal neoplasia. Correlations among these novel biomarkers suggest a possible shared pathway. These findings need replication and could further delineate ESCCs molecular mechanisms of carcinogenesis.
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Affiliation(s)
- John Aversa
- Surgical Oncology Program, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD
| | - Minkyo Song
- Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, MD
| | - Taichi Shimazu
- Epidemiology and Prevention Group, Center for Public Health Sciences, National Cancer Center, Tokyo, Japan
| | - Manami Inoue
- Epidemiology and Prevention Group, Center for Public Health Sciences, National Cancer Center, Tokyo, Japan
| | - Hadrien Charvat
- Epidemiology and Prevention Group, Center for Public Health Sciences, National Cancer Center, Tokyo, Japan
| | - Taiki Yamaji
- Epidemiology and Prevention Group, Center for Public Health Sciences, National Cancer Center, Tokyo, Japan
| | - Norie Sawada
- Epidemiology and Prevention Group, Center for Public Health Sciences, National Cancer Center, Tokyo, Japan
| | - Ruth M Pfeiffer
- Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, MD
| | - Parisa Karimi
- Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, MD
| | - Sanford M Dawsey
- Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, MD
| | - Charles S Rabkin
- Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, MD
| | - Shoichiro Tsugane
- Epidemiology and Prevention Group, Center for Public Health Sciences, National Cancer Center, Tokyo, Japan
| | - M Constanza Camargo
- Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, MD
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Du L, Lei L, Zhao X, He H, Chen E, Dong J, Zeng Y, Yang J. The Interaction of Smoking with Gene Polymorphisms on Four Digestive Cancers: A Systematic Review and Meta-Analysis. J Cancer 2018; 9:1506-1517. [PMID: 29721061 PMCID: PMC5929096 DOI: 10.7150/jca.22797] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/12/2017] [Accepted: 01/22/2018] [Indexed: 12/15/2022] Open
Abstract
The main purpose of this study was to perform a meta-analysis to assess the interaction between smoking and nine genes (GSTM1, GSTT1, GSTP1, CYP1A1, NAT2, SULT1A1, hOGG1, XRCC1 and p53) on colorectal cancer, gastric cancer, liver cancer and oesophageal cancer. Published articles from the PubMed, ISI and EMBASE databases were retrieved. A total of 67 case-control studies or nested case-control studies were identified for the analysis. The pooled jodds ratio (OR) with 95% confidence interval (CI) was calculated using the random effect model. The overall study showed that the GSTM1 polymorphism was associated with the risk of the four digestive cancers among Asian population (OR 1.284, 95% CI: 1.122-1.470, p: 0). Subgroup analyses by cancer site showed that GSTM1 null genotype increased the gastric cancer risk in total population (OR 1.335, 95% CI: 1.145-1.556, p: 0). However, the association of GSTM1 null genotype with the oesophageal cancer risk was found in smokers (OR 1.382, 95% CI: 1.009-1.894, p:0.044), but not in non-smokers (OR 1.250, 95% CI: 0.826-1.891, p:0.290). Moreover, smokers with the CYP1A1 IIe462Val polymorphism were at an increased cancer risk in Asian population (OR=1.585, 95% CI 1.029-2.442, p: 0.037). None of the other gene-smoking interactions was observed in the above cancers. This meta-analysis reveals two potential gene-smoking interactions, one is between smoking and GSTM1 on oesophageal cancer, and the other is between smoking and CYP1A1 IIe462Val on the four cancers in Asian population. Future studies need to be conducted to verify the conclusions.
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Affiliation(s)
- Le Du
- Key Laboratory of Resources Biology and Biotechnology in Western China, Ministry of Education, College of Life Science, Northwest University, Xi'an 710069, China.,Institute of Preventive Genomic Medicine, Xi'an 710069, China
| | - Lei Lei
- Key Laboratory of Resources Biology and Biotechnology in Western China, Ministry of Education, College of Life Science, Northwest University, Xi'an 710069, China.,Institute of Preventive Genomic Medicine, Xi'an 710069, China
| | - Xiaojuan Zhao
- Key Laboratory of Resources Biology and Biotechnology in Western China, Ministry of Education, College of Life Science, Northwest University, Xi'an 710069, China.,Institute of Preventive Genomic Medicine, Xi'an 710069, China
| | - Hongjuan He
- Key Laboratory of Resources Biology and Biotechnology in Western China, Ministry of Education, College of Life Science, Northwest University, Xi'an 710069, China.,Institute of Preventive Genomic Medicine, Xi'an 710069, China
| | - Erfei Chen
- Key Laboratory of Resources Biology and Biotechnology in Western China, Ministry of Education, College of Life Science, Northwest University, Xi'an 710069, China.,Institute of Preventive Genomic Medicine, Xi'an 710069, China
| | - Jing Dong
- Key Laboratory of Resources Biology and Biotechnology in Western China, Ministry of Education, College of Life Science, Northwest University, Xi'an 710069, China.,Institute of Preventive Genomic Medicine, Xi'an 710069, China
| | - Yuan Zeng
- Key Laboratory of Resources Biology and Biotechnology in Western China, Ministry of Education, College of Life Science, Northwest University, Xi'an 710069, China.,Institute of Preventive Genomic Medicine, Xi'an 710069, China
| | - Jin Yang
- Key Laboratory of Resources Biology and Biotechnology in Western China, Ministry of Education, College of Life Science, Northwest University, Xi'an 710069, China.,Institute of Preventive Genomic Medicine, Xi'an 710069, China
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Tasnim T, Al-Mamun MMA, Nahid NA, Islam MR, Apu MNH, Bushra MU, Rabbi SNI, Nahar Z, Chowdhury JA, Ahmed MU, Islam MS, Hasnat A. Genetic variants of SULT1A1 and XRCC1 genes and risk of lung cancer in Bangladeshi population. Tumour Biol 2017; 39:1010428317729270. [PMID: 29110586 DOI: 10.1177/1010428317729270] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/15/2022] Open
Abstract
Lung cancer is one of the most frequently occurring cancers throughout the world as well as in Bangladesh. This study aimed to correlate the prognostic and/or predictive value of functional polymorphisms in SULT1A1 (rs9282861) and XRCC1 (rs25487) genes and lung cancer risk in Bangladeshi population. A case-control study was conducted which comprises 202 lung cancer patients and 242 healthy volunteers taking into account the age, sex, and smoking status. After isolation of genomic DNA, genotyping was done by polymerase chain reaction-restriction fragment length polymorphism method and the lung cancer risk was evaluated as odds ratio that was adjusted for age, sex, and smoking status. A significant association was found between SULT1A1 rs9282861 and XRCC1 rs25487 polymorphisms and lung cancer risk. In case of rs9282861 polymorphism, Arg/His (adjusted odds ratio = 5.06, 95% confidence interval = 3.05-8.41, p < 0.05) and His/His (adjusted odds ratio = 3.88, 95% confidence interval = 2.20-6.82, p < 0.05) genotypes were strongly associated with increased risk of lung cancer in comparison to the Arg/Arg genotype. In case of rs25487 polymorphism, Arg/Gln heterozygote (adjusted odds ratio = 4.57, 95% confidence interval = 2.79-7.46, p < 0.05) and Gln/Gln mutant homozygote (adjusted odds ratio = 4.99, 95% confidence interval = 2.66-9.36, p < 0.05) were also found to be significantly associated with increased risk of lung cancer. This study demonstrates that the presence of His allele and Gln allele in case of SULT1A1 rs9282861 and XRCC1 rs25487, respectively, involve in lung cancer prognosis in Bangladeshi population.
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Affiliation(s)
- Tasnova Tasnim
- 1 Department of Clinical Pharmacy and Pharmacology, Faculty of Pharmacy, University of Dhaka, Dhaka, Bangladesh.,3 Department of Pharmacy, University of Asia Pacific, Dhaka, Bangladesh
| | - Mir Md Abdullah Al-Mamun
- 1 Department of Clinical Pharmacy and Pharmacology, Faculty of Pharmacy, University of Dhaka, Dhaka, Bangladesh
| | - Noor Ahmed Nahid
- 1 Department of Clinical Pharmacy and Pharmacology, Faculty of Pharmacy, University of Dhaka, Dhaka, Bangladesh
| | - Md Reazul Islam
- 1 Department of Clinical Pharmacy and Pharmacology, Faculty of Pharmacy, University of Dhaka, Dhaka, Bangladesh
| | - Mohd Nazmul Hasan Apu
- 1 Department of Clinical Pharmacy and Pharmacology, Faculty of Pharmacy, University of Dhaka, Dhaka, Bangladesh
| | - Most Umme Bushra
- 1 Department of Clinical Pharmacy and Pharmacology, Faculty of Pharmacy, University of Dhaka, Dhaka, Bangladesh
| | | | - Zabun Nahar
- 3 Department of Pharmacy, University of Asia Pacific, Dhaka, Bangladesh
| | - Jakir Ahmed Chowdhury
- 4 Department of Pharmaceutical Technology, Faculty of Pharmacy, University of Dhaka, Dhaka, Bangladesh
| | - Maizbha Uddin Ahmed
- 1 Department of Clinical Pharmacy and Pharmacology, Faculty of Pharmacy, University of Dhaka, Dhaka, Bangladesh
| | - Mohammad Safiqul Islam
- 5 Department of Pharmacy, Noakhali Science and Technology University, Noakhali, Bangladesh
| | - Abul Hasnat
- 1 Department of Clinical Pharmacy and Pharmacology, Faculty of Pharmacy, University of Dhaka, Dhaka, Bangladesh
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Abstract
Esophageal cancer (EC) is one of the most common malignancies in low- and medium-income countries and represents a disease of public health importance because of its poor prognosis and high mortality rate in these regions. The striking variation in the prevalence of EC among different ethnic groups suggests a significant contribution of population-specific environmental and dietary factors to susceptibility to the disease. Although individuals within a demarcated geographical area are exposed to the same environment and share similar dietary habits, not all of them will develop the disease; thus genetic susceptibility to environmental risk factors may play a key role in the development of EC. A wide range of xenobiotic-metabolizing enzymes are responsible for the metabolism of carcinogens introduced via the diet or inhaled from the environment. Such dietary or environmental carcinogens can bind to DNA, resulting in mutations that may lead to carcinogenesis. Genes involved in the biosynthesis of these enzymes are all subject to genetic polymorphisms that can lead to altered expression or activity of the encoded proteins. Genetic polymorphisms may, therefore, act as molecular biomarkers that can provide important predictive information about carcinogenesis. The aim of this review is to discuss our current knowledge on the genetic risk factors associated with the development of EC in different populations; it addresses mainly the topics of genetic polymorphisms, gene-environment interactions, and carcinogenesis. We have reviewed the published data on genetic polymorphisms of enzymes involved in the metabolism of xenobiotics and discuss some of the potential gene-environment interactions underlying esophageal carcinogenesis. The main enzymes discussed in this review are the glutathione S-transferases (GSTs), N-acetyltransferases (NATs), cytochrome P450s (CYPs), sulfotransferases (SULTs), UDP-glucuronosyltransferases (UGTs), and epoxide hydrolases (EHs), all of which have key roles in the detoxification of environmental and dietary carcinogens. Finally, we discuss recent advances in the study of genetic polymorphisms associated with EC risk, specifically with regard to genome-wide association studies, and examine possible challenges of case-control studies that need to be addressed to better understand the interaction between genetic and environmental factors in esophageal carcinogenesis.
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Affiliation(s)
- Marco Matejcic
- a International Centre for Genetic Engineering and Biotechnology, Cape Town Component , Observatory , Cape Town , South Africa , and
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10
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Chen BH, Wang CC, Hou YH, Mao YC, Yang YS. Mechanism of sulfotransferase pharmacogenetics in altered xenobiotic metabolism. Expert Opin Drug Metab Toxicol 2015; 11:1053-71. [DOI: 10.1517/17425255.2015.1045486] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/05/2022]
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11
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Xiao J, Zheng Y, Zhou Y, Zhang P, Wang J, Shen F, Fan L, Kolluri VK, Wang W, Yan X, Wang M. Sulfotransferase SULT1A1 Arg213His polymorphism with cancer risk: a meta-analysis of 53 case-control studies. PLoS One 2014; 9:e106774. [PMID: 25225888 PMCID: PMC4165769 DOI: 10.1371/journal.pone.0106774] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/10/2014] [Accepted: 07/30/2014] [Indexed: 01/14/2023] Open
Abstract
Background The SULT1A1 Arg213His (rs9282861) polymorphism is reported to be associated with many kinds of cancer risk. However, the findings are conflicting. For better understanding this SNP site and cancer risk, we summarized available data and performed this meta-analysis. Methods Data were collected from the following electronic databases: PubMed, Web of Knowledge and CNKI. The association was assessed by odd ratio (OR) and the corresponding 95% confidence interval (95% CI). Results A total of 53 studies including 16733 cancer patients and 23334 controls based on the search criteria were analyzed. Overall, we found SULT1A1 Arg213His polymorphism can increase cancer risk under heterozygous (OR = 1.09, 95% CI = 1.01–1.18, P = 0.040), dominant (OR = 1.10, 95% CI = 1.01–1.19, P = 0.021) and allelic (OR = 1.08, 95% CI = 1.02–1.16, P = 0.015) models. In subgroup analyses, significant associations were observed in upper aero digestive tract (UADT) cancer (heterozygous model: OR = 1.62, 95% CI = 1.11–2.35, P = 0.012; dominant model: OR = 1.63, 95% CI = 1.13–2.35, P = 0.009; allelic model: OR = 1.52, 95% CI = 1.10–2.11, P = 0.012) and Indians (recessive model: OR = 1.93, 95% CI = 1.22–3.07, P = 0.005) subgroups. Hospital based study also showed marginally significant association. In the breast cancer subgroup, ethnicity and publication year revealed by meta-regression analysis and one study found by sensitivity analysis were the main sources of heterogeneity. The association between SULT1A1 Arg213His and breast cancer risk was not significant. No publication bias was detected. Conclusions The present meta-analysis suggests that SULT1A1 Arg213His polymorphism plays an important role in carcinogenesis, which may be a genetic factor affecting individual susceptibility to UADT cancer. SULT1A1 Arg213His didn't show any association with breast cancer, but the possible risk in Asian population needs further investigation.
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Affiliation(s)
- Juanjuan Xiao
- Department of Biochemical and Molecular Biology, Medical College, Soochow University, Suzhou, Jiangsu, China
| | - Yabiao Zheng
- Department of Biochemical and Molecular Biology, Medical College, Soochow University, Suzhou, Jiangsu, China
| | - Yinghui Zhou
- Department of Biochemical and Molecular Biology, Medical College, Soochow University, Suzhou, Jiangsu, China
| | - Ping Zhang
- Department of Biochemical and Molecular Biology, Medical College, Soochow University, Suzhou, Jiangsu, China
| | - Jianguo Wang
- Department of Biochemical and Molecular Biology, Medical College, Soochow University, Suzhou, Jiangsu, China
| | - Fangyuan Shen
- Department of Biochemical and Molecular Biology, Medical College, Soochow University, Suzhou, Jiangsu, China
| | - Lixia Fan
- Department of Biochemical and Molecular Biology, Medical College, Soochow University, Suzhou, Jiangsu, China
| | - Vijay Kumar Kolluri
- Department of Biochemical and Molecular Biology, Medical College, Soochow University, Suzhou, Jiangsu, China
| | - Weiping Wang
- Department of Biochemical and Molecular Biology, Medical College, Soochow University, Suzhou, Jiangsu, China
| | - Xiaolong Yan
- Department of Thoracic Surgery, Tangdu Hospital, Fourth Military Medical University, Xi'an, Shaanxi, China
- * E-mail: (XLY); (MHW)
| | - Minghua Wang
- Department of Biochemical and Molecular Biology, Medical College, Soochow University, Suzhou, Jiangsu, China
- * E-mail: (XLY); (MHW)
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Li W, Gu M. SULT1A1 Arg213His polymorphism is associated with bladder cancer risk: a meta-analysis. Med Sci Monit 2014; 20:1590-5. [PMID: 25194687 PMCID: PMC4166222 DOI: 10.12659/msm.890822] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/24/2022] Open
Abstract
Background The evidence of an association between the Sulfotransferase 1A1 (SULT1A1) Arg213His polymorphism (rs9282861) and bladder cancer risk is still conflicting. We conducted a meta-analysis to assess the association between this polymorphism and bladder cancer risk. Material/Methods PubMed, EMBASE, HuGE Navigator, and Web of Science databases were searched for correlative articles. The risk (odds ratio, OR) was used to estimate the association between SULT1A1 Arg213His polymorphism and bladder cancer risk. All of the studies used either fixed-effects or random-effects models. For assessing the credibility of an association, we applied the Venice criteria. Results Seven published case-control studies with 1688 cases and 2842 controls were included in this meta-analysis. There were 5 studies of Caucasians and 2 studies of Asians. Four studies reported data on smoking behavior. The percentage of Arg/Arg was higher in Asians and non-smokers than that in Caucasians and smokers, respectively. A significant association of this polymorphism with bladder cancer was found (OR=1.45, 95% CI 1.18–1.78, P=0.0004). In the subgroup analysis by ethnicity, a significant association was found among Caucasians (OR=1.43, 95% CI 1.16–1.77, P=0.0008) but not among Asians (OR=1.89, 95% CI 0.68–5.26, P=0.22). In the subgroup analysis by smoking behavior, increased bladder cancer risk was found in the smokers (OR=1.39, 95% CI 1.01–1.91, P=0.04) and non-smokers (OR=1.74, 95% CI 1.24–2.43, P=0.001). Conclusions In conclusion, this meta-analysis indicated that SULT1A1 Arg213His polymorphism is associated with bladder cancer risk.
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Affiliation(s)
- Wencheng Li
- Department of Urology, Affiliated Nanjing First Hospital, Nanjing Medical University, Nanjing, China (mainland)
| | - Min Gu
- Department of Urology, First Affiliated Hospital, Nanjing Medical University, Nanjing, China (mainland)
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Su CM, Chen MC, Lin IC, Chen HA, Huang MT, Wu CH, Shen KH, Wang YH. Association between the SULT1A1 Arg213His polymorphism and the risk of bladder cancer: a meta-analysis. Tumour Biol 2014; 35:7147-53. [PMID: 24763827 DOI: 10.1007/s13277-014-1954-5] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/08/2013] [Accepted: 04/07/2014] [Indexed: 12/01/2022] Open
Abstract
Several previous studies have investigated the association between the SULT1A1 Arg213His polymorphism and the risk of bladder cancer in various populations. However, these results remain inconsistent. Therefore, we performed this meta-analysis to evaluate the relationship between the SULT1A1 Arg213His polymorphism and the risk of bladder cancer. An extensive literature search was performed to identify all eligible studies regarding this association. The odds ratios (ORs) with 95 % confidence intervals (CIs) were used to estimate the strength of risk under fixed and random effects models. We identified and included eight case-control studies including 2,036 cases and 2,273 controls. No significant association was found between the SULT1A1 Arg213His polymorphism and the risk of bladder cancer under the dominant model; however, those with the SULT1A1 Arg/Arg genotype had a significantly increased risk (OR = 1.218, 95 % CI = 1.067-1.392, P = 0.0044) under the recessive model. In the subgroup analysis of ethnicity, a significant association was observed in Caucasians under the recessive model (OR = 1.269, 95 % CI = 1.069-1.506, P = 0.007). Furthermore, an increased risk of bladder cancer was observed between the Arg213His polymorphism and never smokers in the recessive model (OR = 1.428, 95 % CI = 1.079-1.890, P = 0.013). The results of this meta-analysis indicate that the SULT1A1 Arg213His polymorphism is associated with the risk bladder cancer under a recessive model; however, a possibly higher risk for Caucasians with the Arg/Arg genotype and never smokers needs further investigation.
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Affiliation(s)
- Chih-Ming Su
- Division of General Surgery, Department of Surgery, Taipei Medical University Shuang Ho Hospital, New Taipei City, Taiwan
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Santos SS, Koifman RJ, Ferreira RM, Diniz LF, Brennan P, Boffetta P, Koifman S. SULT1A1 genetic polymorphisms and the association between smoking and oral cancer in a case-control study in Brazil. Front Oncol 2012; 2:183. [PMID: 23264952 PMCID: PMC3524504 DOI: 10.3389/fonc.2012.00183] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/25/2012] [Accepted: 11/14/2012] [Indexed: 11/13/2022] Open
Abstract
INTRODUCTION Oral cancer is a public health problem worldwide, being tobacco and alcohol consumption their main risk factors. Sulfotransferase (SULT) 1A1 (encoded by SULT1A1) is involved in procarcinogens metabolism, such as polycyclic aromatic hydrocarbons (PAHs) present in tobacco smoke. OBJECTIVE The aim of this study was to explore the magnitude of association between SULT1A1 gene Arg(213)His polymorphism and oral cancer, and to explore the interaction between such polymorphism and smoking. METHODS A hospital-based case-control study was carried out in Rio de Janeiro, Brazil, during 1999-2002. Epidemiological data and biological samples were obtained from 202 oral cancer patients and 196 sex and age-frequency matched controls without cancer antecedents. RESULTS No association was observed between Arg(213)His SULT1A1 polymorphism and oral cancer risk in overall analysis (OR = 1.06, 95% CI = 0.71-1.57). The magnitude of association between cigarette smoking and oral cancer was higher in individuals with a SULT1A1(*)1 isoform (wild type, genotype Arg/Arg) (OR = 10.19, 95% CI = 3.90-26.61) than in those with at least one SULT1A1(*)2 allele (genotypes Arg/His + His/His) (OR = 4.50, 95% CI =2.09-9.69). CONCLUSION Our results suggest that Arg(213)His SULT1A1 polymorphism may modulate the association between smoking and oral cancer. However, this association needs to be replicated in other studies: due to modest number of cases and controls, the role of chance in the observed association cannot be ruled out.
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Tung MC, Wang YH, Yeh SD, Wu CC, Chen KC, Huang ZM, Huang MT, Chiou HY. Combined effects of GSTO1 and SULT1A1 polymorphisms and cigarette smoking on urothelial carcinoma risk in a Taiwanese population. J Formos Med Assoc 2012; 113:640-7. [PMID: 25103078 DOI: 10.1016/j.jfma.2012.08.015] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/23/2012] [Revised: 08/17/2012] [Accepted: 08/20/2012] [Indexed: 12/27/2022] Open
Abstract
BACKGROUND/PURPOSE Cigarette smoking is the main risk factor for urothelial carcinoma of the bladder (UCB). Glutathione S-transferase omega 1 (GSTO1) and sulfotransferase 1A1 (SULT1A1) have been reported to be associated with the metabolism of polycyclic aromatic hydrocarbons (PAHs) and aromatic amines. The aim of the present study was to investigate the combined effects of polymorphisms in GSTO1 and SULT1A1 genes and cigarette smoking on UCB risk in a Taiwanese population. METHODS A total of 300 patients with histopathologically confirmed UCB and 233 cancer-free controls were recruited from the Department of Urology of Tung's Taichung Metro Harbor Hospital and Taipei Medical University Hospital. A comprehensive interview was conducted to collect personal information, including demographic characteristics and cigarette smoking status. A multivariate-adjusted logistic regression was performed to estimate the risk of UCB. RESULTS A significantly increased risk of UCB was observed in ever smokers [odds ratio (OR) = 2.3]. The Ala/Ala genotype of the GSTO1 gene and the Arg/Arg genotype of the SULT1A1 gene were associated with a significantly increased risk of UCB, with ORs of 1.8 [95% confidence interval (CI) = 1.2-2.6] and 2.1 (95% CI = 1.6-4.5), respectively. Significantly increased UCB risks were found in heavy smokers with the Ala/Ala genotype of the GSTO1 gene (OR = 4.2) and the Arg/Arg genotype of the SULT1A1 gene (OR = 6.8). Furthermore, a significant synergistic effect in an additive model (OR = 3.5) between the GSTO1 Ala/Ala genotype and the SULT1A1 Arg/Arg genotype on UCB risk was observed. CONCLUSION The present study provided epidemiological evidence for a significantly increased risk of UCB in ever smokers with the Ala/Ala genotype of the GSTO1 gene and the Arg/Arg genotype of the SULT1A1 gene.
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Affiliation(s)
- Min-Che Tung
- Department of Urology, Tung's Taichung MetroHarbor Hospital, Taichung County, Taiwan
| | - Yuan-Hung Wang
- Division of General Surgery, Department of Urology, Shuang Ho Hospital, Taipei Medical University, New Taipei City, Taiwan; Graduate Institute of Clinical Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan
| | - Shauh-Der Yeh
- Department of Urology, Taipei Medical University Hospital, Taipei, Taiwan; Institute of Biomedical Sciences, Academia Sinica, Taipei, Taiwan
| | - Chia-Chang Wu
- Department of Urology, Shuang Ho Hospital, Taipei Medical University, Taipei, Taiwan
| | - Kuan-Chou Chen
- Department of Urology, Shuang Ho Hospital, Taipei Medical University, Taipei, Taiwan
| | - Zhon-Min Huang
- Department of Urology, Tung's Taichung MetroHarbor Hospital, Taichung County, Taiwan
| | - Ming-Te Huang
- Division of General Surgery, Department of Surgery, Shuang Ho Hospital, Taipei Medical University, Taipei, Taiwan
| | - Hung-Yi Chiou
- School of Public Health, College of Public Health and Nutrition, Taipei Medical University, Taipei, Taiwan; Center of Excellence for Cancer Research, Taipei Medical University, Taipei, Taiwan.
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Li K, Ren YW, Wan Y, Yin ZH, Wu W, Zhou BS. SULT1A1 Arg213His polymorphism and susceptibility of environment-related cancers: a meta analysis of 5,915 cases and 7,900 controls. Mol Biol Rep 2011; 39:2597-605. [PMID: 21670965 DOI: 10.1007/s11033-011-1012-y] [Citation(s) in RCA: 9] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/08/2011] [Accepted: 06/02/2011] [Indexed: 11/26/2022]
Abstract
The common genetic polymorphism for SULT1A1 is Arg213His polymorphism, which may affect the sulfation process of various environmental carcinogens and thus is suggested to be related to susceptibility of several cancers. However, studies on the association between SULT1A1 Arg213His polymorphism and cancer susceptibility are inconsistent. To assess the relationship between Arg213His polymorphism and environmental-related cancers systematically, we performed a meta analysis from 20 case-control studies including 5,915 cases and 7,900 controls. The odds ratios (ORs) and 95% confidence intervals (CIs) were used to estimate the strength of risk, we found a significant association between SULT1A1 Arg213His polymorphism and environment-related cancers (for dominant model: OR 1.22, 95% CI 1.07-1.39, P = 0.003). When stratified by ethnicity, a significant risk was observed in Asian cases, compared with controls (for dominant model: OR 1.69, 95% CI 1.17-2.43, P = 0.005). When we chose only smokers in our analysis, we also found a significantly increased risk between Arg213His polymorphism and susceptibility of environment-related cancers for participants exposed to a smoking environment. In conclusion, SULT1A1 Arg213His polymorphism, ethnicity, smoking may modulate environment-related cancer risk. Studies on gene-gene interactions in the sequential or concurrent metabolic pathway and gene-environment interactions need to be further conducted to explore the susceptibility of cancer occurrence.
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Affiliation(s)
- Kun Li
- Department of Epidemiology, School of Public Health, China Medical University, No 92 Beier Road, Heping District, Shenyang, 110001 Liaoning Province, China
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Zhang C, Li JP, Lv GQ, Yu XM, Gu YL, Zhou P. Lack of association of SULT1A1 R213H polymorphism with colorectal cancer: a meta-analysis. PLoS One 2011; 6:e19127. [PMID: 21695180 PMCID: PMC3113796 DOI: 10.1371/journal.pone.0019127] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/07/2011] [Accepted: 03/16/2011] [Indexed: 11/18/2022] Open
Abstract
Background A number of case-control studies were conducted to investigate the association of SULT1A1 R213H polymorphisms with colorectal cancer (CRC) in humans. But the results were not always consistent. We performed a meta-analysis to examine the association between the SULT1A1 R213H polymorphism and CRC. Methods and Findings Data were collected from the following electronic databases: PubMed, Elsevier Science Direct, Excerpta Medica Database, and Chinese Biomedical Literature Database, with the last report up to September 2010. A total of 12 studies including 3,549 cases and 5,610 controls based on the search criteria were involved in this meta-analysis. Overall, no significant association of this polymorphism with CRC was found (H versus R: OR = 1.04, 95%CI = 0.94–1.16, P = 0.46; HR+HH versus RR: OR = 1.01, 95%CI = 0.92–1.11, P = 0.81; HH versus RR+HR: OR = 1.01, 95%CI = 0.74–1.38, P = 0.95; HH versus RR: OR = 1.00, 95%CI = 0.77–1.31, P = 0.98; HR versus RR: OR = 1.01, 95%CI = 0.92–1.11, P = 0.86). In subgroup analysis, we also did not find any significant association in Cauasians (H versus R: OR = 1.02, 95%CI = 0.92–1.15, P = 0.68; HR+HH versus RR: OR = 0.99, 95%CI = 0.91–1.09, P = 0.90; HH versus RR+HR: OR = 1.01, 95%CI = 0.73–1.39, P = 0.97; HH versus RR: OR = 0.99, 95%CI = 0.75–1.31, P = 0.94; HR versus RR: OR = 0.99, 95%CI = 0.90–1.09, P = 0.85). The results were not materially altered after the studies which did not fulfill Hardy-Weinberg equilibrium were excluded (H versus R: OR = 1.06, 95%CI = 0.95–1.19, P = 0.31; HR+HH versus RR: OR = 1.03, 95%CI = 0.93–1.13, P = 0.56; HH versus RR+HR: OR = 1.10, 95%CI = 0.78–1.56, P = 0.57; HH versus RR: OR = 1.09, 95%CI = 0.83–1.44, P = 0.53; HR versus RR: OR = 1.02, 95%CI = 0.92–1.13, P = 0.75). Conclusion This meta-analysis demonstrates that there is no association between the SULT1A1 R213H polymorphism and CRC.
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Affiliation(s)
- Chun Zhang
- Department of General Surgery, The Third Affiliated Hospital to Nantong University, Wuxi, China
- Intensive Care Unit, The Third Affiliated Hospital to Nantong University, Wuxi, China
| | - Jian-Ping Li
- Department of General Surgery, The Third Affiliated Hospital to Nantong University, Wuxi, China
| | - Guo-Qiang Lv
- Department of General Surgery, The Third Affiliated Hospital to Nantong University, Wuxi, China
| | - Xian-Min Yu
- Department of General Surgery, The Third Affiliated Hospital to Nantong University, Wuxi, China
| | - Yuan-Long Gu
- Department of General Surgery, The Third Affiliated Hospital to Nantong University, Wuxi, China
| | - Ping Zhou
- Intensive Care Unit, The Third Affiliated Hospital to Nantong University, Wuxi, China
- * E-mail:
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Arslan S. Genetic polymorphisms of sulfotransferases (SULT1A1 and SULT1A2) in a Turkish population. Biochem Genet 2010; 48:987-94. [PMID: 20936502 DOI: 10.1007/s10528-010-9387-3] [Citation(s) in RCA: 9] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/25/2009] [Accepted: 07/15/2010] [Indexed: 11/30/2022]
Abstract
Sulfotransferases (SULTs) play a significant role in the biotransformation of a variety of xenobiotics and endogenous compounds. SULTs are genetically polymorphic enzymes; to date, 12 human cytosolic SULT isoforms have been identified. This study investigated SULT1A1 and SULT1A2 gene polymorphism using a PCR-RFLP method (n = 303). The frequency of the SULT1A1*1 allele was 76.2% and SULT1A1*2 was 23.8%. The SULT1A1*3 allele could not be identified. The SULT1A2 frequencies were 69.2% (SULT1A2*1), 18.3% (SULT1A2*2), and 12.5% (SULT1A2*3). The SULT1A1 and SULT1A2 loci were in Hardy-Weinberg equilibrium (SULT1A1 χ² = 0.58, P = 0.44; SULT1A2 χ² = 7.28, P = 0.06). Linkage analysis indicated a close linkage between these two genes (χ² = 5.31, P < 0.01); therefore, the statistical hypothesis that SULT1A1 and SULT1A2 alleles are independently distributed was rejected. Additionally, a strongly positive linkage was detected between SULT1A1*2 and SULT1A2*2 alleles in this population (D' = 0.79, χ² = 33.33).
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Affiliation(s)
- Serdal Arslan
- Department of Molecular Biology and Genetics, Cumhuriyet University, Sivas, Turkey.
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Arslan S, Silig Y, Pinarbasi H. An investigation of the relationship between SULT1A1 Arg213His polymorphism and lung cancer susceptibility in a Turkish population. Cell Biochem Funct 2009; 27:211-5. [DOI: 10.1002/cbf.1558] [Citation(s) in RCA: 15] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/24/2022]
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Abstract
Investigations into inherited genetic variations in the DNA code (known as polymorphisms) in the field of oncology have provided preliminary support for an association with cancer risks and outcomes. Early studies have highlighted several genes with this potential predictive and prognostic power. However, these studies have had methodological limitations and have produced inconsistent results, making impractical as yet the routine evaluation of such genetic polymorphisms in general clinical practice. Continued research in this area is essential if we are to be able to soon use genetic polymorphisms to better select patients for targeted anticancer interventions. This review discusses the role of genetic polymorphisms and their association with esophageal cancer risk and prognosis. The article also highlights future directions in this new, emerging field of molecular epidemiology.
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Abstract
The cause of the majority of cancers is poorly understood albeit multifactorial. The ultimate consequence of etiological factors where defined is an alteration within the cellular genotype, which is manifested in the cells acquiring malignant phenotype. There are several environmental carcinogens that contribute to carcinogenesis. These carcinogens are metabolized by a large number of enzymes, including the cyto-chrome P 450 group, glutathione-S-transferase (GST), the uridine glucuronyl transferase (UGT) super-family, alcohol-metabolizing enzymes, sulphatases, etc. These enzymes can either inactivate carcinogens or in some cases generate reactive moieties that lead to carcinogenesis. This review summarises the available evidence regarding the role of xenobiotic metabolic enzymes and their role in cancer epidemiology. The available data and studies have identified correlates between expression of various metabolizing enzymes with risk of malignancies known to be induced by their substrates. The data may have relevance in one population but not for another for a specific malignancy and at times may be conflicting. We believe that with mature data in the future it may be possible to stratify patients by risk.
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Case-control study and meta-analysis of SULT1A1 Arg213His polymorphism for gene, ethnicity and environment interaction for cancer risk. Br J Cancer 2008; 99:1340-7. [PMID: 18854828 PMCID: PMC2570530 DOI: 10.1038/sj.bjc.6604683] [Citation(s) in RCA: 30] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/26/2022] Open
Abstract
Cytosolic sulphotransferase SULT1A1 plays a dual role in the activation of some carcinogens and inactivation of others. A functional polymorphism leading to Arg213His substitution (SULT1A1*2) affects its catalytic activity and thermostability. To study the association of SULT1A1*2 polymorphism with tobacco-related cancers (TRCs), a case–control study comprising 132 patients with multiple primary neoplasm (MPN) involving TRC and 198 cancer-free controls was carried out. One hundred and thirteen MPN patients had at least one cancer in upper aerodigestive tract including lung (UADT-MPN). SULT1A1*2 showed significant risk association with UADT-MPN (odds ratio (OR)=5.50, 95% confidence interval (CI): 1.09, 27.7). Meta-analysis was conducted combining the data with 34 published studies that included 11 962 cancer cases and 14 673 controls in diverse cancers. The SULT1A1*2 revealed contrasting risk association for UADT cancers (OR=1.62, 95% CI: 1.12, 2.34) and genitourinary cancers (OR=0.73, 95% CI: 0.58, 0.92). Furthermore, although SULT1A1*2 conferred significant increased risk of breast cancer to Asian women (OR=1.91, 95% CI: 1.08, 3.40), it did not confer increased risk to Caucasian women (OR=0.92, 95% CI: 0.71, 1.18). Thus risk for different cancers in distinct ethnic groups could be modulated by interaction between genetic variants and different endogenous and exogenous carcinogens.
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Chung YT, Hsieh LL, Chen IH, Liao CT, Liou SH, Chi CW, Ueng YF, Liu TY. Sulfotransferase 1A1 haplotypes associated with oral squamous cell carcinoma susceptibility in male Taiwanese. Carcinogenesis 2008; 30:286-94. [DOI: 10.1093/carcin/bgn283] [Citation(s) in RCA: 15] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/31/2022] Open
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Suzuki H, Morris JS, Li Y, Doll MA, Hein DW, Liu J, Jiao L, Hassan MM, Day RS, Bondy ML, Abbruzzese JL, Li D. Interaction of the cytochrome P4501A2, SULT1A1 and NAT gene polymorphisms with smoking and dietary mutagen intake in modification of the risk of pancreatic cancer. Carcinogenesis 2008; 29:1184-91. [PMID: 18499698 PMCID: PMC2443278 DOI: 10.1093/carcin/bgn085] [Citation(s) in RCA: 45] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/02/2023] Open
Abstract
Aromatic amines, N-nitroso compounds and heterocyclic amines are suspected human pancreatic carcinogens. Cytochrome P450 (CYP) 1A2, N-acetyltransferase (NAT) 1, NAT2 and sulfotransferase (SULT) are enzymes involved in the metabolism of these carcinogens. To test the hypothesis that genetic variations in carcinogen metabolism modify the risk of pancreatic cancer (PC), we investigated the effect of single-nucleotide polymorphisms (SNPs) of the CYP1A2, NAT1, NAT2 and SULT1A1 gene on modification of the risk of PC in a hospital-based study of 755 patients with pancreatic adenocarcinoma and 636 healthy frequency-matched controls. Smoking and dietary mutagen exposure information was collected by personal interviews. Genotypes were determined using the polymerase chain reaction–restriction fragment length polymorphism and Taqman methods. Odds ratios (ORs) and 95% confidence intervals (CIs) were estimated using unconditional multivariate logistic regression analysis. We observed no significant main effects of any of these genes on the risk of PC. The CYP1A2 and NAT1 but not SULT1A1 and NAT2 genotypes showed significant interactions with heavy smoking in women not men. In contrast, a significant interaction between NAT1 genotype and dietary mutagen intake on modifying the risk of PC were observed among men but not women. The OR (95% CI) of PC was 2.23 (1.33–3.72) and 2.54 (1.51–4.25) for men having the NAT1*10 and a higher intake of 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine and benzo[a]pyrene, respectively, compared with individuals having no NAT1*10 or a lower intake of these dietary mutagens. These data suggest the existence of gender-specific susceptibility to tobacco carcinogen and dietary mutagen exposure in PC.
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Affiliation(s)
- Hideo Suzuki
- Department of Gastrointestinal Medical Oncology, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, TX 77030, USA
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Further evidence for null association of phenol sulfotransferase SULT1A1 polymorphism with prostate cancer risk: a case–control study of familial prostate cancer in a Japanese population. Int Urol Nephrol 2008; 40:947-51. [DOI: 10.1007/s11255-008-9364-5] [Citation(s) in RCA: 9] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/12/2008] [Accepted: 03/04/2008] [Indexed: 11/25/2022]
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Swindell WR. Comparative analysis of microarray data identifies common responses to caloric restriction among mouse tissues. Mech Ageing Dev 2007; 129:138-53. [PMID: 18155270 DOI: 10.1016/j.mad.2007.11.003] [Citation(s) in RCA: 52] [Impact Index Per Article: 2.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/28/2007] [Revised: 10/27/2007] [Accepted: 11/05/2007] [Indexed: 10/22/2022]
Abstract
Caloric restriction has been extensively investigated as an intervention that both extends lifespan and delays age-related disease in mammals. In mice, much interest has centered on evaluating gene expression changes induced by caloric restriction (CR) in particular tissue types, but the overall systemic effect of CR among multiple tissues has been examined less extensively. This study presents a comparative analysis of microarray datasets that have collectively examined the effects of CR in 10 different tissue types (liver, heart, muscle, hypothalamus, hippocampus, white adipose tissue, colon, kidney, lung and cochlea). Using novel methods for comparative analysis of microarray data, detailed comparisons of the effects of CR among tissues are provided, and 28 genes for which expression response to CR is most shared among tissues are identified. These genes characterize common responses to CR, which consist of both activation and inhibition of stress-response pathways. With respect to liver tissue, transcriptional effects of CR exhibited surprisingly little overlap with those of aging, and a variable degree of overlap with the potential CR-mimetic drug resveratrol. These analyses shed light on the systemic transcriptional activity associated with CR diets, and also illustrate new approaches for comparative analysis of microarray datasets in the context of aging biology.
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Affiliation(s)
- William R Swindell
- Department of Pathology, University of Michigan, 109 Zina Pitcher Place, Ann Arbor, MI 48103, United States.
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Hiyama T, Yoshihara M, Tanaka S, Chayama K. Genetic polymorphisms and esophageal cancer risk. Int J Cancer 2007; 121:1643-58. [PMID: 17674367 DOI: 10.1002/ijc.23044] [Citation(s) in RCA: 159] [Impact Index Per Article: 8.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/15/2022]
Abstract
The aim of this paper is to review and evaluate, in a comprehensive manner, the published data regarding the contribution of genetic polymorphisms to risk of esophageal cancer, including squamous cell carcinoma (SCC) and adenocarcinoma, in humans. All relevant studies available in MEDLINE and published before February 2007 were identified. Studies carried out in humans and that compared esophageal cancer patients with at least 1 standard control group were considered for analysis. One-hundred studies and 3 meta-analyses were identified. Eighty (80%) studies were conducted in Asian countries, particularly China including Taiwan (60 (60%) studies). The most intensively examined genes were those encoding carcinogen metabolic enzymes. The most widely studied gene was GSTM1 (15 studies), followed by ALDH2 (11 studies). ALDH2, MTHFR C677T, CYP1A1 Ile/Val, CYP1A1MspI, CYP2E1, GSTP1, GSTM1 and GSTT1 were examined by meta-analyses and significant relations were found between ALDH2*1*2 and the CYP1A1 Val allele and increased risk of esophageal cancer. In addition, increased risk of esophageal SCC was consistently associated with the ADH2*1*2 and the p53 codon 72 Pro/Pro genotypes. Cohort studies that simultaneously consider multiple genetic and environmental factors possibly involved in esophageal carcinogenesis are needed to ascertain not only the relative contribution of these factors to tumor development but also the contributions of their putative interactions.
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Affiliation(s)
- Toru Hiyama
- Health Service Center, Hiroshima University, Higashihiroshima, Japan.
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Wong RH, Hu CW, Yeh CY, Chao MR, Chen CC, Huang JH, Chang SH, Lee SI, Lee HS. Sulfotransferase 1A1 and glutathione S-transferase P1 genetic polymorphisms modulate the levels of urinary 8-hydroxy-2'-deoxyguanosine in betel quid chewers. Arch Toxicol 2007; 82:313-21. [PMID: 17912498 DOI: 10.1007/s00204-007-0248-8] [Citation(s) in RCA: 12] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/11/2007] [Accepted: 09/11/2007] [Indexed: 10/22/2022]
Abstract
Betel quid chewing has been associated with several human cancers. However, the role of betel quid in carcinogenesis remains uncertain. Piper betel contains high concentrations of safrole (an inducer of DNA oxidative damage). Safrole may be metabolized by hepatic sulfotransferase 1A1 (SULT1A1), or glutathione S-transferases (GSTM1, GSTT1, and GSTP1). Thus, we investigated the association of genetic polymorphisms of SULT1A1, GSTM1, GSTT1, and GSTP1 with DNA oxidative damage among betel quid chewers. A biomarker for oxidative stress, urinary 8-hydroxy-2'-deoxyguanosine (8-OHdG) level, was analyzed using isotope-dilution LC-MS/MS in 64 betel quid chewers and 129 non-betel quid chewers. Data on demographics and habits (smoking, alcohol drinking, and betel quid chewing) were obtained from questionnaires. Our results revealed that urinary 8-OHdG level was higher in chewers with SULT1A1 Arg-His genotype than in chewers with SULT1A1 Arg-Arg genotype. Urinary 8-OHdG level was also higher in chewers with GSTP1 Ile-Ile genotype. Furthermore, the combined effect of SULT1A1 and GSTP1 genotypes on urinary 8-OHdG was evaluated. Non-chewers with both SULT1A1 Arg-Arg and GSTP1 Val-Val/Ile-Val (reference group) had the lowest mean level (3.6 ng/mg creatinine), whereas chewers with either SULT1A1 Arg-His or GSTP1 Ile-Ile had the highest 8-OHdG mean level (6.2 ng/mg creatinine; vs. reference group, P = 0.04). Chewers with both of SULT1A1 Arg-Arg and GSTP1 Val-Val/Ile-Val (4.6 ng/mg creatinine), and non-chewers with either SULT1A1 Arg-His or GSTP1 Ile-Ile (4.7 ng/mg creatinine) had a moderately increased 8-OHdG level. Thus, the susceptible SULT1A1 and GSTP1 genotypes may modulate increased DNA oxidative stress elicited by betel-quid chewing.
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Affiliation(s)
- Ruey-Hong Wong
- Department of Public Health, College of Health Care and Management, Chung Shan Medical University, No. 110 Chien-Kuo N. Road Sec. 1, Taichung, Taiwan.
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Wang YH, Lee YH, Tseng PT, Shen CH, Chiou HY. Human NAD(P)H:quinone oxidoreductase 1 (NQO1) and sulfotransferase 1A1 (SULT1A1) polymorphisms and urothelial cancer risk in Taiwan. J Cancer Res Clin Oncol 2007; 134:203-9. [PMID: 17619904 DOI: 10.1007/s00432-007-0271-4] [Citation(s) in RCA: 20] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/10/2007] [Accepted: 06/22/2007] [Indexed: 10/23/2022]
Abstract
PURPOSE To investigate whether the NAD(P)H:quinone oxidoreductase 1 (NQO1) and sulfotransferase 1A1 (SULT1A1) polymorphisms are associated with urothelial cancer (UC) risk in Taiwan. METHODS In this study, 600 study subjects (including 300 UC patients and 300 cancer-free controls) were recruited from September 1998 to December 2005. We analyzed the NQO1 and SULT1A1 polymorphisms by the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method. A comprehensive interview was conducted to collect information, including baseline characteristics and cigarette smoking status. We used an unconditional multivariate logistic regression to calculate the odds ratio (OR) and 95% confidence interval (CI). RESULTS We found a significantly increased UC risk in study subjects with the NQO1 C/T and T/T genotypes (OR = 1.5; 95% CI: 1.03-2.1). A significantly increased UC risk was found in those with the SULT1A1 G/G genotype (OR = 2.0; 95% CI: 1.3-3.2). Subjects who had ever smoked with either the NQO1 C/T and T/T genotypes or the SULT1A1 G/G genotype had significantly increased UC risks, showing ORs of 3.0 and 5.3, respectively. Subjects carrying both the NQO1 C/T and T/T genotypes and the SULT1A1 G/G genotype had a significantly increased UC risk (OR = 3.7; 95% CI, 1.4-9.7). Moreover, those who had ever smoked with both the NQO1 C/T and T/T genotypes and the SULT1A1 G/G genotype had the highest UC risk (OR = 8.6; 95% CI: 2.5-29.7). CONCLUSIONS These findings suggest that NQO1 and SULT1A1 polymorphisms are associated with the risk of UC, particularly among those who have ever smoked.
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Affiliation(s)
- Yuan-Hung Wang
- School of Public Health, Topnotch Stroke Research Center, Taipei Medical University, 250 Wu-Hsing Street, Taipei 110, Taiwan
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Bardakci F, Arslan S, Bardakci S, Binatli AO, Budak M. Sulfotransferase 1A1 (SULT1A1) polymorphism and susceptibility to primary brain tumors. J Cancer Res Clin Oncol 2007; 134:109-14. [PMID: 17605044 DOI: 10.1007/s00432-007-0256-3] [Citation(s) in RCA: 15] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/24/2007] [Accepted: 06/05/2007] [Indexed: 12/01/2022]
Abstract
PURPOSE Sulfotransferase 1A1 is a member of sulfotransferase family that plays an important role in the biotransformation of numerous carcinogenic and mutagenic compounds through sulfation. The present study has investigated the association between SULT1A1 polymorphism and primary brain tumor incidence. METHODS SULT1A1 genotypes were successfully detected using the PCR-RFLP assay in 60 primary brain tumor patients and 156 hospital-based healthy control individuals with no history of cancer or precancerous disorder. RESULTS There was a significant difference in genotypes distribution (GG vs. GA + AA) between brain tumor patients (GG genotype frequency = 48.3%) and control population (GG genotype frequency = 65.4%; OR = 2.019, 95% CI = 1.103-3.695; P = 0.022). In order to determine the association between SULT1A1 polymorphism and specific types of brain tumors, the patients were classified according to the type of brain tumors they suffer from: glial and non-glial. Results of the statistical analyses of each group of patients in comparison with the control individuals showed a significant difference only between SULT1A1 polymorphism and non-glial brain tumors (OR = 2.615; 95% CI = 1.192-5.739; P = 0.014) but glial tumors (OR = 1.535; 95% CI = 0.688-3.425; P = 0.293). When non-glial tumors were classified as meningiomal and others (pituitary adenoma, craniopharyngioma, acoustic neuroma and hemangioblastoma), statistical analysis showed that this significance is only due to the meningiomal tumors (OR = 3.238; CI = 1.205-8.704; P = 0.015). We also estimated a reduced risk of brain tumor in non-smokers (OR = 1.700; CI = 0.800-3.615) in comparison to smokers (OR = 2.773; CI = 0.993-7.749), but this was not statistically significant. CONCLUSION Our findings have suggested that there was a significant association between brain tumor and SULT1A1*2 allele (A allele that is also known as His allele) and this allele is an important risk factor in the development of meningiomal brain tumors.
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Affiliation(s)
- F Bardakci
- Department of Biology, Faculty of Science and Literature, Adnan Menderes University, 09100 Aydin, Turkey.
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Ung D, Nagar S. Variable sulfation of dietary polyphenols by recombinant human sulfotransferase (SULT) 1A1 genetic variants and SULT1E1. Drug Metab Dispos 2007; 35:740-6. [PMID: 17293380 DOI: 10.1124/dmd.106.013987] [Citation(s) in RCA: 44] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/22/2022] Open
Abstract
Human cytosolic sulfotransferases (SULTs) catalyze the sulfate conjugation of several important endo- and xenobiotics. Among the superfamily of SULT enzymes, SULT1A1 catalyzes the sulfation of small planar phenolic compounds, whereas SULT1E1 has a major role in estrogen conjugation. The human SULT1A1 gene has common single nucleotide polymorphisms that define three allozymes, SULT1A1*1, *2, and *3. The enzyme kinetics of SULT1A1 allozymes and SULT1E1 were characterized for the polyphenolic substrates apigenin, chrysin, epicatechin, quercetin, and resveratrol. Purified recombinant SULT proteins were generated in a baculoviral-insect cell system, and incubated in vitro with each substrate to determine catalytic activity. The effect of polyphenol sulfation was examined in mammalian cell lines stably expressing SULT1E1. For all polyphenols investigated, "normal-activity" SULT1A1*1 allozyme had significantly greater Vmax estimates than SULT1E1, and allele-specific differences in SULT1A1-mediated sulfation were observed. The polymorphic SULT1A1*2 allozyme exhibited low activity toward apigenin, epicatechin, and resveratrol. SULT1A1*1 and *3 acted as normal-activity allozymes for these substrates. Altered cellular proliferation was observed in MCF-7 cells stably expressing SULT1E1 upon treatment with chrysin, quercetin, or resveratrol, thus suggesting inactivation of these compounds by SULT1E1. These results suggest an important role for SULT isozymes and their pharmacogenetics in polyphenol disposition.
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Affiliation(s)
- Din Ung
- Department of Pharmaceutical Sciences, Temple University School of Pharmacy, 3307 North Broad St., Philadelphia, PA 19140, USA
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Hempel N, Gamage N, Martin JL, McManus ME. Human cytosolic sulfotransferase SULT1A1. Int J Biochem Cell Biol 2007; 39:685-9. [PMID: 17110154 DOI: 10.1016/j.biocel.2006.10.002] [Citation(s) in RCA: 38] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/04/2006] [Revised: 09/21/2006] [Accepted: 10/03/2006] [Indexed: 11/24/2022]
Abstract
Sulfonation is an important conjugation reaction required for a range of biological processes including phase II metabolism, whereby sulfo-conjugation renders a compound more hydrophilic to aid its excretion. The major enzyme responsible for xenobiotic sulfonation is the widely expressed cytosolic sulfotransferase SULT1A1. The SULT1A1 crystal structure has provided insights into this enzyme's substrate specificity and catalytic function, including its role in the sulfonation of endogenous substrates such as oestrogens. Contrary to its metabolic role, SULT1A1 can also bioactivate compounds; it is known to sulfonate pro-carcinogens such as hydroxymethyl polycyclic aromatic hydrocarbons leading to highly reactive intermediates capable of forming DNA adducts, potentially resulting in mutagenesis. Given the role of SULT1A1 in these diverse functions and the discovery of allelic variants with differing catalytic activities, this enzyme has been the focus of numerous polymorphic studies investigating the link between inter-individual SULT1A1 variance and the etiology of a variety of cancers.
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Affiliation(s)
- Nadine Hempel
- Department of Medicine, Duke University Medical Center, Durham, NC 27710, USA
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Pachouri SS, Sobti RC, Kaur P, Singh J, Gupta SK. Impact of polymorphism in sulfotransferase gene on the risk of lung cancer. ACTA ACUST UNITED AC 2006; 171:39-43. [PMID: 17074589 DOI: 10.1016/j.cancergencyto.2006.06.017] [Citation(s) in RCA: 22] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/15/2006] [Accepted: 06/22/2006] [Indexed: 11/23/2022]
Abstract
Sulfotransferases (SULTs) are very important multifunctional enzymes that catalyze sulfonate conjugation, which is an important pathway in the phase II metabolism of numerous endogenous and exogenous compounds. Sulfotransferase 1A1 (SULT1A1) is active toward a wide range of substrates, including environmental and tobacco carcinogens. This case-control study involved collection of peripheral blood samples (2-5 mL) of 103 lung cancer patients and 122 controls from North Indian subjects. The SULT1A1 polymorphism was determined by using a polymerase chain reaction-restriction fragment length polymorphism method. The association between polymorphisms in the SULT1A1 gene with the risk of lung cancer was estimated by computing odds ratios (OR) and 95% confidence intervals (95% CI), using a multivariate logistic regression analysis. We observed marginally increased risk for mutant genotype (AA) of SULT1A1 for lung cancer (OR = 1.4, 95% CI = 0.48-4.06). A statistically significant association was found for smokers between either of two SULT1A1 genotypes, GA (OR = 10.3, 95% CI = 3.48-31.78, P = 0.000002) or AA (OR = 3.9, 95% CI = 1.99-7.81, P = 0.0002), and lung cancer. The present study indicates that the SULT1A1 genotype may play an important role in the risk of developing lung cancer, especially in cigarette smokers.
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Swinney R, Hsu S, Tomlinson G. Phase I and Phase II Enzyme Polymorphisms and Childhood Cancer. J Investig Med 2006; 54:303-20. [PMID: 17134614 DOI: 10.2310/6650.2006.05062] [Citation(s) in RCA: 15] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/18/2022]
Abstract
Childhood cancers continue to be challenging clinical entities whose etiology, demographic characteristics, clinical progression, treatment efficacy, and outcomes remain incompletely understood. Research suggests that multiple environmental and genetic factors may play crucial roles in the pathophysiology of many of these malignancies. Recent attention has been directed to the role of carcinogen metabolizing enzymes in the etiology and progression of cancer in both adults and children due to their multitude of polymorphic variants and their intimate interaction with environmental factors. In particular, xenobiotic metabolizing enzymes (XME), which are intimately involved in the activation and deactivation of many environmental carcinogens, have become an area of significant interest. Traditionally, these enzymes have been classified into either phase I or phase II enzymes depending on their substrates, activity, and occasionally based on their sequence in the metabolic pathways, and have been demonstrated to have numerous polymorphic variants. Phase I enzymes predominantly consist of cytochrome enzymes responsible for mixed function oxidase activity, whereas phase II enzymes are frequently conjugation reactions necessary for drug metabolism or the further metabolism of phase I enzyme products. Current research has discovered numerous interactions between polymorphisms in these enzymes and changes in cancer susceptibility, treatment efficacy, and clinical outcomes in childhood cancer. Furthermore, studies of polymorphisms in these enzymes have demonstrated to have synergistic/antagonistic interactions with other XME polymorphisms and demonstrate variable influences on disease pathophysiology depending on the patient's ethnic background and environmental milieu. Continuing research on the role of polymorphisms in phase I and phase II enzymes will likely further elucidate the intimate role of these polymorphisms with environmental factors in the etiology of childhood cancer.
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Affiliation(s)
- Ryan Swinney
- University of Texas Southwestern Medical Center, Dallas, TX 75390, USA
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35
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Nagar S, Walther S, Blanchard RL. Sulfotransferase (SULT) 1A1 polymorphic variants *1, *2, and *3 are associated with altered enzymatic activity, cellular phenotype, and protein degradation. Mol Pharmacol 2006; 69:2084-92. [PMID: 16517757 DOI: 10.1124/mol.105.019240] [Citation(s) in RCA: 121] [Impact Index Per Article: 6.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/22/2022] Open
Abstract
The superfamily of sulfotransferase (SULT) enzymes catalyzes the sulfate conjugation of several pharmacologically important endo- and xenobiotics. SULT1A1 catalyzes the sulfation of small planar phenols such as neurotransmitters, steroid hormones, acetaminophen, and p-nitrophenol (PNP). Genetic polymorphisms in the human SULT1A1 gene define three alleles, SULT1A1*1, *2, and *3. The enzyme activities of the SULT1A1 allozymes were studied with a variety of substrates, including PNP, 17beta-estradiol, 2-methoxyestradiol, catecholestrogens, the antiestrogen 4-hydroxytamoxifen (OHT), and dietary flavonoids. Using purified recombinant SULT1A1 protein, marked differences in *1, *2, and *3 activity toward every substrate studied were noted. Substrate inhibition was observed for most substrates. In general, the trend in V(max) estimates was *1 > *3 > *2; however, V(max)/K(m) estimate trends varied with substrate. In MCF-7 cells stably expressing either SULT1A1*1 or *2, the antiestrogenic response to OHT was found to be allele-specific: the cells expressing *2 exhibited a better antiproliferative response. The intracellular stability of the *1 and *2 allozymes was examined in insect as well as mammalian cells. The SULT1A1*2 protein had a shorter half-life than the *1 protein. In addition, the *2 protein was ubiquitinated to a greater extent than *1, suggesting increased degradation via a proteasome pathway. The results of this study suggest marked differences in activity of polymorphic SULT1A1 variants, including SULT1A1*3, toward a variety of substrates. These differences are potentially critical for understanding interindividual variability in drug response and toxicity, as well as cancer risk and incidence.
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Affiliation(s)
- Swati Nagar
- Fox Chase Cancer Center, Philadelphia, PA, USA
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Boccia S, Cadoni G, La Torre G, Arzani D, Volante M, Cattel C, Gianfagna F, Paludetti G, Almadori G, Ricciardi G. A case-control study investigating the role of sulfotransferase 1A1 polymorphism in head and neck cancer. J Cancer Res Clin Oncol 2006; 132:466-72. [PMID: 16575574 DOI: 10.1007/s00432-006-0093-9] [Citation(s) in RCA: 11] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/24/2005] [Accepted: 03/02/2006] [Indexed: 10/24/2022]
Abstract
PURPOSE Sulfotransferases (SULT) 1A1 detoxify and bio-activate a broad spectrum of substrates including xenobiotics. The SULT1A1 gene possesses a G-->A polymorphism that results in an Arg to His substitution at codon 213, with the His allele having a low activity. The purpose of this study was to evaluate whether SULT1A1 Arg213His polymorphisms are risk factors for head and neck squamous cell carcinoma (SCCHN). METHODS A total of 124 consecutive primary SCCHN patients and 249 age- and sex-matched hospital controls were enrolled in this study. Genomic DNA was isolated from peripheral blood lymphocytes and genotyping was performed by PCR-RFLP. A comprehensive epidemiological interview was conducted on all participants to collect their lifestyle data. RESULTS The His/His frequencies in cases and controls were 6.5% (8/123) and 3.6% (9/247), respectively (P=0.049). Multivariate logistic regression analysis showed a significant association of SCCHN and His/His genotype (OR=3.60; 95% CI=1.01-12.88). This association was stronger amongst older people, alcohol and low fruit consumers. The resulted SULT1A1 His/His genotype also associated with a higher risk of neck node positive status (OR=5.82; 95% CI=1.10-30.68). CONCLUSIONS These preliminary findings show for the first time that the SULT1A1 His (213) allele is a possible risk factor for head and neck cancer development.
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Affiliation(s)
- Stefania Boccia
- Institute of Hygiene, Catholic University of the Sacred Heart, L.go F. Vito 1, 00168 Rome, Italy.
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Sun XF, Ahmadi A, Arbman G, Wallin A, Asklid D, Zhang H. Polymorphisms in sulfotransferase 1A1 and glutathione S-transferase P1 genes in relation to colorectal cancer risk and patients' survival. World J Gastroenterol 2006; 11:6875-9. [PMID: 16425401 PMCID: PMC4723394 DOI: 10.3748/wjg.v11.i43.6875] [Citation(s) in RCA: 29] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
Abstract
AIM To examine whether polymorphisms in SULT1A1 and GSTP1 genes contribute to colorectal cancer development and whether they are associated with clinicopathological variables are not well identified. METHODS We examined the genotypes of 125 colorectal cancer patients and 666 healthy controls in a Swedish population by using PCR-restriction fragment length polymorphism (RFLP). RESULTS SULT1A1 *2/*2 genotype (OR=2.49, 95%CI=1.48-4.19, P=0.0002) and *2 allele (OR=1.56, 95%CI=1.16-2.10, P=0.002) had an effect on colorectal cancer susceptibility, while GSTP1 genotype was without effect. However, GSTP1 G-type predicted a worse prognosis in the patients independently of gender, age, Dukes' stage, growth pattern, and differentiation (P=0.03). CONCLUSION Polymorphism in SULT1A1 may predispose to colorectal cancer and GSTP1 may be a biological indicator of prognosis in the patients.
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Affiliation(s)
- Xiao-Feng Sun
- Department of Oncology, Institute of Biomedicine and Surgery, University of Linkoping, S-581 85 Linkoping, Sweden.
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Lilla C, Risch A, Verla-Tebit E, Hoffmeister M, Brenner H, Chang-Claude J. SULT1A1 genotype and susceptibility to colorectal cancer. Int J Cancer 2006; 120:201-6. [PMID: 17013894 DOI: 10.1002/ijc.22156] [Citation(s) in RCA: 24] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/06/2022]
Abstract
Several procarcinogens that are present in cooked red meat and tobacco smoke are substrates for sulfotransferase 1A1 (SULT1A1). The association between environmental exposures and colorectal cancer risk may be modified by individual differences in the metabolism. Thus, we investigated the effect of a common polymorphism in the SULT1A1 gene associated with decreased enzyme activity on the susceptibility to colorectal cancer in a population-based case-control study. Patients (505) and 604 age- and sex-matched controls provided detailed risk factor information and were genotyped for SULT1A1 G638A using a fluorescence-based melting curve analysis method. Multivariate logistic regression analysis was used to estimate colorectal cancer risk associated with environmental exposures by SULT1A1 genotype. SULT1A1 genotype was not an independent risk factor for colorectal cancer. Risk of colorectal cancer associated with frequent consumption of red meat was significantly elevated among carriers of the SULT1A1*2 allele but not increased among subjects with the SULT1A1*1/*1 genotype (odds ratio (OR) 2.1, 95% confidence interval (CI) 1.1-4.1 and OR 1.0, 95% CI 0.5-2.1, respectively). Colorectal cancer risk associated with 30+ pack-years of active smoking was higher among carriers of the SULT1A1*2 allele (OR 1.7, 95% CI 1.0-3.2) than among individuals with the SULT1A1*1/*1 genotype (OR 1.1, 95% CI 0.6-2.1). Our results do not support a main effect of SULT1A1 genotype with regard to colorectal cancer but suggest that individuals with the low activity SULT1A1*2 allele may be at higher risk following carcinogen exposure than those with the SULT1A1*1/*1 genotype.
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Affiliation(s)
- Carmen Lilla
- Division of Clinical Epidemiology, German Cancer Research Center, Heidelberg, Germany
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Stiborová M, Arlt VM, Henderson CJ, Wolf CR, Frei E, Schmeiser HH, Phillips DH. Molecular mechanism of genotoxicity of the environmental pollutant 3-nitrobenzanthrone. Biomed Pap Med Fac Univ Palacky Olomouc Czech Repub 2005; 149:191-7. [PMID: 16601755 DOI: 10.5507/bp.2005.025] [Citation(s) in RCA: 9] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/07/2023] Open
Abstract
3-Nitrobenzanthrone (3-NBA) is a suspected human carcinogen identified in diesel exhaust and air pollution. This article reviews the results of our laboratories showing which of the phase I and II enzymes are responsible for 3-NBA genotoxicity, participating in activation of 3-NBA and its human metabolite, 3-aminobenzanthrone (3-ABA), to species generating DNA adducts. Among the phase I enzymes, the most of the activation of 3-NBA in vitro is attributable to cytosolic NAD(P)H:quinone oxidoreductase (NQO1), while N,O-acetyltransferase (NAT), NAT2, followed by NAT1, sulfotransferase (SULT), SULT1A1 and, to a lesser extent, SULT1A2 are the major phase II enzymes activating 3- NBA. To evaluate the importance of hepatic cytosolic enzymes in relation to microsomal NADPH:cytochrome P450 (CYP) oxidoreductase (POR) in the activation of 3-NBA in vivo, we treated hepatic POR-null and wild-type C57BL/6 mice with 3-NBA or 3-ABA. The results indicate that 3-NBA is predominantly activated by cytosolic nitroreductases such as NQO1 rather than microsomal POR. In the case of 3-ABA, CYP1A1/2 enzymes are essential for the oxidative activation of 3-ABA in liver. However, cells in the extrahepatic organs have the metabolic capacity to activate 3-ABA to form DNA adducts, independently from CYP-mediated oxidation in the liver. Peroxidases such as prostaglandin H synthase, lactoperoxidase, myeloperoxidase, abundant in several extrahepatic tissues, generate DNA adducts, which are formed in vivo by 3-ABA or 3-NBA. The results suggest that both CYPs and peroxidases may play an important role in metabolism of 3-ABA to reactive species forming DNA adducts, participating in genotoxicity of this compound and its parental counterpart, 3-NBA.
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Affiliation(s)
- Marie Stiborová
- Department of Biochemistry, Charles University, Albertov 2030, 12840 Prague 2, Czech Republic.
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Dandara C, Li DP, Walther G, Parker MI. Gene-environment interaction: the role of SULT1A1 and CYP3A5 polymorphisms as risk modifiers for squamous cell carcinoma of the oesophagus. Carcinogenesis 2005; 27:791-7. [PMID: 16272171 DOI: 10.1093/carcin/bgi257] [Citation(s) in RCA: 43] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/14/2022] Open
Abstract
An imbalance in the activities of enzymes involved in the metabolism, conjugation and transport of xenobiotics may account for the variability in susceptibility to the development of complex diseases such as cancer between different population groups. In this study we investigated a functional polymorphism in the SULT1A1 gene in 245 patients and 288 controls. Previous studies have shown that the 638G-->A polymorphism that results in the substitution of arginine by histidine at codon 213 (SULT1A1*2) results in decreased SULT1A1 activity. The same group of samples used in this study had been previously genotyped for CYP3A5 genetic polymorphisms. Among Black subjects the burning of wood or charcoal for cooking and keeping warm was significantly associated with increased risk for oesophageal cancer (OC) (AOR, 15.2; P=0.001) as was the consumption of home-brewed beer (AOR, 6.97; P=0.0001). Among the Mixed Ancestry group, tobacco smoking combined with alcohol consumption were significantly associated with higher risk for OC (AOR, 5.18; P=0.0005). In both Blacks and Mixed Ancestry subjects, starting to smoke below the age of 20 years was associated with significantly increased risk for OC (AOR, 3.5 among the Blacks and AOR, 12 among the Mixed Ancestry). The homozygous SULT1A1*2/*2 genotype was associated with increased risk for OC among smokers. The SULT1A1*2/*2 genotype in combination with the CYP3A5 heterozygous genotypes was associated with significantly increased risk for OC (AOR, 3.60; P=0.001) with the risk being even higher among smokers compared with non-smokers. The above findings confirm the association between alcohol consumption and tobacco smoking with increased risk for OC. The genotype results show that SULT1A1*2/*2 genotype is associated with increased risk for OC among subjects exposed to tobacco-smoke-related carcinogens.
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Affiliation(s)
- Collet Dandara
- UCT/MRC-Oesophageal Cancer Research Group, Division of Medical Biochemistry, Institute of Infectious Disease and Molecular Medicine (IIDMM), Groote Schuur Hospital, Faculty of Health Sciences, University of Cape Town, South Africa
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Yang G, Gao YT, Cai QY, Shu XO, Cheng JR, Zheng W. Modifying Effects of Sulfotransferase 1A1 Gene Polymorphism on the Association of Breast Cancer Risk with Body Mass Index or Endogenous Steroid Hormones. Breast Cancer Res Treat 2005; 94:63-70. [PMID: 16175316 DOI: 10.1007/s10549-005-7280-2] [Citation(s) in RCA: 20] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/25/2022]
Abstract
Sulfotransferase (SULT) 1A1 is involved in the inactivation and elimination of estrogens and catechol estrogens. A common functional polymorphism (Arg213His) has been linked in our previous study of postmenopausal Caucasian women to an elevated risk of breast cancer and the association appeared to be modified by factors related to high endogenous estrogen exposures. We further evaluated this polymorphism and levels of BMI and steroid hormones in association with breast cancer risk in a population-based case-control study of Chinese women, involving 1102 incident cases aged 25-64 years and 1147 age-matched population controls. The SULT1A1 genotype was not associated with overall breast cancer risk in this population. A possible association was suggested for postmenopausal breast cancer (adjusted odds ratio [OR] = 1.4, 95% CI = 0.9-2.1 for subject carrying the variant His allele). The SULT1A1 genotype was found to significantly modify postmenopausal breast cancer risk associated with a high BMI (>or=25 kg/m2) (p for interaction = 0.02), with an adjusted OR of 3.6 (95% CI = 1.5-8.7) for women with the Arg/His genotype compared with 1.1 (0.8-1.5) for women with the Arg/Arg genotype (no His/His genotype was identified in this study population). Similarly, the risk associated with a long duration (>or=30 years) of menstruation also substantially differed by the SULT1A1 genotype (p for interaction = 0.05), with an OR of 4.0 (95% CI = 1.3-12.8) for women with the Arg/His genotype and 1.4 (0.8-2.5) for women with the Arg/Arg genotype. Positive associations with blood levels of steroid hormones were also found generally to be more pronounced among women carrying the His allele. No similar effect modification was found for premenopausal breast cancer, however. These data suggest that the SULT1A1 Arg213His polymorphism may modify the effect of endogenous sex hormone exposures on postmenopausal breast cancer risk.
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Affiliation(s)
- Gong Yang
- Department of Medicine, Center for Health Services Research and Vanderbilt-Ingram Cancer Center, Vanderbilt University Medical Center, Nashville, TN 37232-8300, USA.
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Boccia S, Persiani R, La Torre G, Rausei S, Arzani D, Gianfagna F, Romano-Spica V, D'Ugo D, Ricciardi G. Sulfotransferase 1A1 polymorphism and gastric cancer risk: a pilot case-control study. Cancer Lett 2005; 229:235-43. [PMID: 16137826 DOI: 10.1016/j.canlet.2005.06.035] [Citation(s) in RCA: 33] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/21/2005] [Revised: 06/28/2005] [Accepted: 06/29/2005] [Indexed: 12/20/2022]
Abstract
Sulfotransferases (SULT) catalyse both the bioactivation and detoxification of a wide range of promutagens and carcinogens. The SULT1A1 gene possesses a G-->A polymorphism that results in a Arg to His substitution at codon 213, and the His allele has been shown to have a low activity and thermal stability. To test the hypothesis that individuals carrying the variant allele may be at high risk of gastric cancer, we identified the SULT1A1 Arg213His genotype by a PCR-based RFLP in a preliminary study of 76 gastric adenocarcinoma patients that underwent curative gastrectomy and 260 age and sex-matched controls from a medical centre in Rome. A comprehensive epidemiological interview was conducted on all participants to collect lifestyle data. The prognostic significance of the SULT1A1 Arg213His polymorphism with respect to staging, differentiation and histological type of gastric cancer was also evaluated. The frequencies of His/His in cases and controls were 11.9% (9/76) and 5% (13/260), respectively (P=0.025). After adjusting for substance use, age, gender and physical activity, individuals with His/His showed a 3.32 fold increased risk of developing gastric cancer compared to those with Arg/Arg (95% CI=1.17-9.45). This positive association was more pronounced amongst males, alcohol drinkers, current smokers and consumers of grilled/barbecued meat and, unexpectedly, amongst individuals with a high intake of fruit. A statistically significant association was also found between the diffuse type of gastric cancer and the heterozygous SULT1A1 genotype. Our preliminary findings suggest for the first time that the SULT1A1 His213 allele may be important in the development of gastric cancer, with other factors modulating such effect.
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Affiliation(s)
- Stefania Boccia
- Institute of Hygiene, Catholic University of Sacred Heart, L.go F.Vito, 1, 00168 Rome, Italy.
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Lin YC, Wu DC, Lee JM, Hsu HK, Kao EL, Yang CH, Wu MT. The association between microsomal epoxide hydrolase genotypes and esophageal squamous-cell-carcinoma in Taiwan: interaction between areca chewing and smoking. Cancer Lett 2005; 237:281-8. [PMID: 16029924 DOI: 10.1016/j.canlet.2005.06.010] [Citation(s) in RCA: 18] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/06/2004] [Revised: 06/02/2005] [Accepted: 06/06/2005] [Indexed: 12/16/2022]
Abstract
One hundred and forty-five ESCC patients and 352 controls were recruited from three hospitals in Taiwan to determine the association between esophageal squamous-cell-carcinoma (ESCC) and microsomal epoxide hydrolase (mEH) genotypes at Thy113His and His139Arg. Stratified by their exposures, the His113His genotype was a significant protective factor for ESCC in areca chewers and tobacco smokers. Stratified by His113 polymorphisms, the risk of contracting ESCC for participants with His113His who chewed areca and smoked was >50% less than for those with Thy113Thy. We suggest that the mEH His113His genotype can differentiate the association between smoking, areca chewing, and ESCC.
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Affiliation(s)
- Ying-Chu Lin
- The Graduate Institute of Dental Science, Kaohsiung Medical University, Kaohsiung, Taiwan, ROC
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Rovito PM, Morse PD, Spinek K, Newman N, Jones RF, Wang CY, Haas GP. Heterocyclic amines and genotype of N-acetyltransferases as risk factors for prostate cancer. Prostate Cancer Prostatic Dis 2005; 8:69-74. [PMID: 15685255 DOI: 10.1038/sj.pcan.4500780] [Citation(s) in RCA: 37] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/02/2023]
Abstract
A variety of carcinogenic heterocyclic amines are produced during the cooking of meat at high temperatures. These carcinogens are metabolized by N-acetyltransferases (NAT), which are polymorphic in the population. This study examined associations between prostate cancer (PCa) and the consumption of different kinds of meat, heterocyclic amine intake and NAT genotypes. PCa patients and controls were recruited in the Syracuse, NY area. Levels of meat and heterocyclic amine intakes were determined from validated surveys and NAT genotypes were determined by the sequences of PCR-amplified DNA from buccal swabs. A total of 152 cases and 161 controls were eligible for analysis. There was an association between PCa and history of PCa in the first-degree blood relatives (OR = 4.59, 95% CI 2.21-9.70), and family history of bladder cancer (P < 0.02). However, there was no association with the history of other cancers. There was no association between PCa and either 2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline (MeIQx), 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) intake, or NAT1 and NAT2 genotypes. However, there was a trend of association with MeIQx and with rapid NAT2 and NAT1*10 in combination with PhIP. A new NAT1 allele with a frequency of one out of 544 chromosomes was found in the Caucasian subjects.
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Affiliation(s)
- P M Rovito
- Department of Urology, SUNY Upstate Medical University, 750 East Adams Street, Syracuse, NY 13210, USA
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Arlt VM, Stiborova M, Henderson CJ, Osborne MR, Bieler CA, Frei E, Martinek V, Sopko B, Wolf CR, Schmeiser HH, Phillips DH. Environmental pollutant and potent mutagen 3-nitrobenzanthrone forms DNA adducts after reduction by NAD(P)H:quinone oxidoreductase and conjugation by acetyltransferases and sulfotransferases in human hepatic cytosols. Cancer Res 2005; 65:2644-52. [PMID: 15805261 DOI: 10.1158/0008-5472.can-04-3544] [Citation(s) in RCA: 97] [Impact Index Per Article: 4.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/16/2022]
Abstract
3-Nitrobenzanthrone (3-nitro-7H-benz[de]anthracen-7-one, 3-NBA) is a potent mutagen and suspected human carcinogen identified in diesel exhaust and air pollution. We compared the ability of human hepatic cytosolic samples to catalyze DNA adduct formation by 3-NBA. Using the (32)P-postlabeling method, we found that 12/12 hepatic cytosols activated 3-NBA to form multiple DNA adducts similar to those formed in vivo in rodents. By comparing 3-NBA-DNA adduct formation in the presence of cofactors of NAD(P)H:quinone oxidoreductase (NQO1) and xanthine oxidase, most of the reductive activation of 3-NBA in human hepatic cytosols was attributed to NQO1. Inhibition of adduct formation by dicoumarol, an NQO1 inhibitor, supported this finding and was confirmed with human recombinant NQO1. When cofactors of N,O-acetyltransferases (NAT) and sulfotransferases (SULT) were added to cytosolic samples, 3-NBA-DNA adduct formation increased 10- to 35-fold. Using human recombinant NQO1 and NATs or SULTs, we found that mainly NAT2, followed by SULT1A2, NAT1, and, to a lesser extent, SULT1A1 activate 3-NBA. We also evaluated the role of hepatic NADPH:cytochrome P450 oxidoreductase (POR) in the activation of 3-NBA in vivo by treating hepatic POR-null mice and wild-type littermates i.p. with 0.2 or 2 mg/kg body weight of 3-NBA. No difference in DNA binding was found in any tissue examined (liver, lung, kidney, bladder, and colon) between null and wild-type mice, indicating that 3-NBA is predominantly activated by cytosolic nitroreductases rather than microsomal POR. Collectively, these results show the role of human hepatic NQO1 to reduce 3-NBA to species being further activated by NATs and SULTs.
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Affiliation(s)
- Volker M Arlt
- Section of Molecular Carcinogenesis, Institute of Cancer Research, Sutton, Surrey, United Kingdom.
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Choi JY, Lee KM, Park SK, Noh DY, Ahn SH, Chung HW, Han W, Kim JS, Shin SG, Jang IJ, Yoo KY, Hirvonen A, Kang D. Genetic Polymorphisms of SULT1A1 and SULT1E1 and the Risk and Survival of Breast Cancer. Cancer Epidemiol Biomarkers Prev 2005; 14:1090-5. [PMID: 15894657 DOI: 10.1158/1055-9965.epi-04-0688] [Citation(s) in RCA: 45] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/16/2022] Open
Abstract
We examined whether common single nucleotide polymorphisms (SNP) in SULT1A1 (c.779G>A, *14A>G, and *85C>T) and SULT1E1 (IVS1-447C>A, IVS4-1653T>C, and *959G>A) genes influenced the risk and survival of breast cancer. Our study population consisted of 989 histologically confirmed sporadic breast cancer patients and 1,054 controls without history of cancer recruited from three teaching hospitals in Seoul. Odds ratios (OR) and 95% confidence intervals (95% CI) were estimated by logistic regression model. In the survival analysis for 529 breast cancer patients with completed treatments, the hazard ratios (HR) were calculated with Cox proportional hazard model. Women with the SULT1E1 *959 GA/AA genotype had a moderately decreased breast cancer risk compared with those with the GG genotypes (OR, 0.8; 95% CI, 0.70-1.00). When the haplotypes were considered, the homozygous *959 AA genotype together with the IVS4-1653 T>C base change (CTA-CCA haplotype) was associated with halved breast cancer risk (OR, 0.5; 95% CI, 0.24-0.88) compared with the wild type CTG-CTG haplotype. No other significant overall association was observed between the SULT1A1 and SULT1E1 SNPs nor haplotypes and breast cancer risk. When stratified by survival, patients with the SULT1E1 IVS4-1653 TC/CC genotypes showed a >3-fold risk of recurrence (HR, 3.2; 95% CI, 1.39-7.48) compared with those with the TT genotype. Moreover, when the haplotypes were considered, the SULT1E1 *959 G>A base change together with the IVS4-1653 T>C base change (CTG-CCA haplotype) was associated with a >4-fold risk of breast cancer (OR, 4.2; 95% CI, 1.15-15.15). These findings suggest that genetic polymorphisms of SULT1E1 are associated with increased risk and a disease free survival of breast cancer in Korean women.
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Affiliation(s)
- Ji-Yeob Choi
- Department of Preventive Medicine, Cancer Research Institute, Seoul National University College of Medicine, 28 Yongon-Dong Chongno-Gu, Seoul 110-799, Korea
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Phylogenomic approaches to common problems encountered in the analysis of low copy repeats: the sulfotransferase 1A gene family example. BMC Evol Biol 2005; 5:22. [PMID: 15752422 PMCID: PMC555591 DOI: 10.1186/1471-2148-5-22] [Citation(s) in RCA: 18] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/07/2004] [Accepted: 03/07/2005] [Indexed: 11/30/2022] Open
Abstract
Background Blocks of duplicated genomic DNA sequence longer than 1000 base pairs are known as low copy repeats (LCRs). Identified by their sequence similarity, LCRs are abundant in the human genome, and are interesting because they may represent recent adaptive events, or potential future adaptive opportunities within the human lineage. Sequence analysis tools are needed, however, to decide whether these interpretations are likely, whether a particular set of LCRs represents nearly neutral drift creating junk DNA, or whether the appearance of LCRs reflects assembly error. Here we investigate an LCR family containing the sulfotransferase (SULT) 1A genes involved in drug metabolism, cancer, hormone regulation, and neurotransmitter biology as a first step for defining the problems that those tools must manage. Results Sequence analysis here identified a fourth sulfotransferase gene, which may be transcriptionally active, located on human chromosome 16. Four regions of genomic sequence containing the four human SULT1A paralogs defined a new LCR family. The stem hominoid SULT1A progenitor locus was identified by comparative genomics involving complete human and rodent genomes, and a draft chimpanzee genome. SULT1A expansion in hominoid genomes was followed by positive selection acting on specific protein sites. This episode of adaptive evolution appears to be responsible for the dopamine sulfonation function of some SULT enzymes. Each of the conclusions that this bioinformatic analysis generated using data that has uncertain reliability (such as that from the chimpanzee genome sequencing project) has been confirmed experimentally or by a "finished" chromosome 16 assembly, both of which were published after the submission of this manuscript. Conclusion SULT1A genes expanded from one to four copies in hominoids during intra-chromosomal LCR duplications, including (apparently) one after the divergence of chimpanzees and humans. Thus, LCRs may provide a means for amplifying genes (and other genetic elements) that are adaptively useful. Being located on and among LCRs, however, could make the human SULT1A genes susceptible to further duplications or deletions resulting in 'genomic diseases' for some individuals. Pharmacogenomic studies of SULT1Asingle nucleotide polymorphisms, therefore, should also consider examining SULT1A copy number variability when searching for genotype-phenotype associations. The latest duplication is, however, only a substantiated hypothesis; an alternative explanation, disfavored by the majority of evidence, is that the duplication is an artifact of incorrect genome assembly.
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Zhu Y, Spitz MR, Amos CI, Lin J, Schabath MB, Wu X. An evolutionary perspective on single-nucleotide polymorphism screening in molecular cancer epidemiology. Cancer Res 2004; 64:2251-7. [PMID: 15026370 DOI: 10.1158/0008-5472.can-03-2800] [Citation(s) in RCA: 85] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/16/2022]
Abstract
Given that there are millions of single-nucleotide polymorphisms (SNPs) in the entire human genome, a major difficulty faced by scientists in planning costly population-based genotyping is to choose target SNPs that are most likely to affect phenotypic functions and ultimately contribute to disease development. Although it is widely accepted that sequences with important functionality tend to be less variable across species because of selective pressure, to what extent evolutionary conservation is mirrored by epidemiological outcome has never been demonstrated. In this study, we surveyed odds ratios detected for 46 SNPs in 39 different cancer-related genes from 166 molecular epidemiological studies. The conservation levels of amino acid that these SNPs affected were calculated as a tolerance index by comparing sequences from different species. Our results provide evidence of a significant relationship between the detected odds ratios associated with cancer risk and the conservation levels of the SNP-affected amino acids (P = 0.002; R(2) = 0.06). Tolerance indices were further calculated for 355 nonsynonymous SNPs identified in 90 human DNA repair genes, of which 103 caused amino acid changes in very conserved positions. Our findings support the concept that SNPs altering the conserved amino acids are more likely to be associated with cancer susceptibility. Using such a molecular evolutionary approach may hold great promise for prioritizing SNPs to be genotyped in future molecular epidemiological studies.
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Affiliation(s)
- Yong Zhu
- Department of Epidemiology, The University of Texas M. D. Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, TX 77030, USA
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Fang FM, Tsai WL, Chiu HC, Kuo WR, Hsiung CY. Quality of life as a survival predictor for esophageal squamous cell carcinoma treated with radiotherapy. Int J Radiat Oncol Biol Phys 2004; 58:1394-404. [PMID: 15050315 DOI: 10.1016/j.ijrobp.2003.09.100] [Citation(s) in RCA: 74] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/19/2003] [Revised: 09/02/2003] [Accepted: 09/03/2003] [Indexed: 11/12/2022]
Abstract
PURPOSE Accumulating reports suggest that quality of life (QOL) may predict survival in cancer patients. In this study, we longitudinally investigated whether the QOL data assessed before, during, and after treatment are prognostic for the survival of patients with esophageal squamous cell carcinoma treated with primary radiotherapy (RT). METHODS AND MATERIALS A total of 110 consecutive new esophageal squamous cell carcinoma patients treated with primary RT were studied. The European Organization for the Research and Treatment of Cancer questionnaire QLQ-C30 (in the Taiwan Chinese version) plus the scales concerning dysphagia and odynophagia were completed before, during, and 2 months after RT. Cox proportional hazards models were used to analyze the impact of clinical and QOL variables on survival. RESULTS A clinical model that included clinical and sociodemographic variables to predict survival using multivariate analysis revealed weight loss, American Joint Committee on Cancer stage, and radiation dose to be statistically significant survival predictors. For QOL scores before RT, physical functioning was the most significant survival predictor. The 2-year survival rate was 30% for patients with a physical functioning score of > or =80.0 compared with a survival rate of 20% for those with a score of <80.0. The QOL scores during RT did not significantly correlate with survival. Of the QOL scores 2 months after RT, the dysphagia symptom scale was the most significant survival predictor. Improvement in dysphagia was observed in 43.0% of patients during RT and in 48.4% of patients 2 months after RT. A dysphagia-free status was found in 35.5% of patients 2 months after RT. The 2-year survival rate was 54.5% for patients without dysphagia 2 months after RT compared with 14.3% for those with dysphagia (p <0.001). CONCLUSION The data provide evidence to support the correlation of patient-reported QOL scores with survival. Pretreatment physical functioning might be a surrogate marker of an unrecognized biologic prognostic factor. The poor survival outcome for patients with persistent dysphagia after treatment implies that local control remains the main issue to overcome in treating esophageal cancer with RT.
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Affiliation(s)
- Fu-Min Fang
- Department of Radiation Oncology, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung Hsien, Taiwan.
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Han DF, Zhou X, Hu MB, Wang CH, Xie W, Tan XD, Zheng F, Liu F. Sulfotransferase 1A1 (SULT1A1) polymorphism and breast cancer risk in Chinese women. Toxicol Lett 2004; 150:167-77. [PMID: 15093672 DOI: 10.1016/j.toxlet.2004.01.012] [Citation(s) in RCA: 27] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/07/2003] [Revised: 12/19/2003] [Accepted: 01/19/2004] [Indexed: 02/04/2023]
Abstract
BACKGROUND Sulfonation catalyzed by sulfotransferase enzymes plays an important role in chemical defense mechanisms against various xenobiotics but also bioactivates carcinogens. A major human sulfotransferase, SULT1A1, catalyzes the sulfation of a variety of phenolic and estrogenic compounds. A functional polymorphism of the SULT1A1 gene has been implicated in a decreased activity and thermostability when the wild-type arginine (Arg) at codon 213 is substituted by a histidine (His). METHODS We investigated the association between the His allele and the risk breast cancer in 213 cases and 430 matched controls in Chinese women, and the interaction between His allele and endogenous estrogen and dietary mutagens exposure factors were also determined by use of logistic regression analysis. RESULTS There was no significant difference in genotypes between the cancer patients and control populations. However, the frequency of the His allele in cases (13.6%) were significant higher than that in controls (9.5%), P = 0.03. Compared with women carrying the Arg/Arg genotype, the adjusted odds ratio (OR) of Arg/His was 1.48 (95% CI = 0.59-3.31) and His/His was 2.28 (95% CI = 0.69-9.58), P trend was 0.04. The adjusted OR of Arg/His + His/His was 2.60 (95% CI = 1.12-6.05). His allele strengthen the effect of endogenous estrogen exposure with interaction index r > 1, and weaken the effect of heterocyclic amines and polycyclic aromatic hydrocarbons derived from dietary with interaction index r > 1, both were multiplicative interaction model. CONCLUSIONS Our findings suggest that the SULT1A1 His allele was positively associated with the risk of breast cancer in Chinese women. And there was interaction between SULT1A1 polymorphism and related exposure factors.
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Affiliation(s)
- Ding-Fen Han
- Department of Clinical Epidemiology, Public Health School of Wuhan University, Wuhan, China.
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