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Mohammadi H, Momeni Roochi M, Rezaei F, Garajei A, Heidar H, Ghaderi B, Sadeghi M. Association between the CYP1A1 MspI polymorphism and risk of head and neck cancer: a meta-analysis. Sci Rep 2022; 12:1527. [PMID: 35087125 PMCID: PMC8795428 DOI: 10.1038/s41598-022-05274-z] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/14/2021] [Accepted: 01/10/2022] [Indexed: 12/24/2022] Open
Abstract
The studies recommended the relationship between lots of polymorphisms with the head and neck cancers (HNCs) risk. Herein, we reported the association between the CYP1A1 MspI polymorphism and the risk of HNC in an updated meta-analysis. The PubMed/MEDLINE, Web of Science, Cochrane Library, and Scopus databases were searched until March 31, 2021, without any restrictions. Odds ratios (ORs) and 95% confidence intervals (CIs) were applied to assess a relationship between CYP1A1 MspI polymorphism and the HNC risk based on five applied genetic models by RevMan 5.3 software. Other analyses (sensitivity analysis, meta-regression, and bias analysis) were performed by CMA 2.0 software. Trial sequential analysis (TSA) was done by TSA software (version 0.9.5.10 beta). Among the databases and other sources, 501 recorded were identified that at last, 29 studies were obtained for the analysis. The pooled ORs were 1.28 (95%CI 1.09, 1.51; P = 0.003), 1.68 (95%CI 1.16, 2.45; P = 0.007), 1.24 (95%CI 1.03, 1.50; P = 0.02), 1.26 (95%CI 1.07, 1.48; P = 0.005), and 1.66 (95%CI 1.27, 2.16; P = 0.0002) for allelic, homozygous, heterozygous, recessive, and dominant models, respectively. Therefore, the m2 allele and m1/m2 and m2/m2 genotypes had significantly increased risks in HNC patients. With regards to stable results and enough samples, the findings of the present meta-analysis recommended that there was an association between CYP1A1 MspI polymorphism and the HNC risk.
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Affiliation(s)
- Hady Mohammadi
- Department of Oral and Maxillofacial Surgery, Fellowship in Maxillofacial Trauma, Health Services, Kurdistan University of Medical Sciences, Sanandaj, 6617713446, Iran
| | - Mehrnoush Momeni Roochi
- Department of Oral and Maxillofacial Surgery, Fellowship in Maxillofacial Trauma, School of Dentistry, Tehran University of Medical Sciences, Tehran, 1439955991, Iran
| | - Farzad Rezaei
- Department of Oral and Maxillofacial Surgery, School of Dentistry, Kermanshah University of Medical Sciences, Kermanshah, 6713954658, Iran
| | - Ata Garajei
- Department of Head and Neck Surgical Oncology and Reconstructive Surgery, The Cancer Institute, Scholl of Medicine, Tehran University of Medical Sciences, Tehran, 1439955991, Iran
| | - Hosein Heidar
- Department of Oral and Maxillofacial Surgery, Fellowship in Maxillofacial Trauma, School of Dentistry, Tehran University of Medical Sciences, Tehran, 1439955991, Iran
| | - Bayazid Ghaderi
- Department of Internal Medicine, Cancer and Immunology Research Center, School of Medicine, Kurdistan University of Medical Sciences, Sanandaj, 6617913446, Iran
| | - Masoud Sadeghi
- Department of Biology, Science and Research Branch, Islamic Azad University, Tehran, 1477893855, Iran.
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Differential Expression of Prostaglandin I2 Synthase Associated with Arachidonic Acid Pathway in the Oral Squamous Cell Carcinoma. JOURNAL OF ONCOLOGY 2018; 2018:6301980. [PMID: 30532780 PMCID: PMC6250001 DOI: 10.1155/2018/6301980] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 07/17/2018] [Accepted: 10/16/2018] [Indexed: 12/11/2022]
Abstract
Introduction Differential expression of genes encoding cytochrome P450 (CYP) and other oxygenases enzymes involved in biotransformation mechanisms of endogenous and exogenous compounds can lead to oral tumor development. Objective We aimed to identify the expression profile of these genes, searching for susceptibility biomarkers in oral squamous cell carcinoma. Patients and Methods Sixteen oral squamous cell carcinoma samples were included in this study (eight tumor and eight adjacent non-tumor tissues). Gene expression quantification was performed using TaqMan Array Human CYP450 and other Oxygenases 96-well plate (Applied Biosystems) by real time qPCR. Protein quantification was performed by ELISA and IHC methods. Bioinformatics tools were used to find metabolic pathways related to the enzymes encoded by differentially expressed genes. Results. CYP27B1, CYP27A1, CYP2E1, CYP2R1, CYP2J2, CYP2U1, CYP4F12, CYP4X1, CYP4B1, PTGIS, ALOX12, and MAOB genes presented differential expression in the oral tumors. After correction by multiple tests, only the PTGIS (Prostaglandin I2 Synthase) gene presented significant differential expression (P < 0.05). The PTGIS gene and protein were reduced in oral tumors. Conclusion PTGIS presents downexpression in oral tumors. PTGIS play an important role in the arachidonic acid metabolism. Arachidonic acid and/or metabolites are derived from this pathway, which can influence the regulation of important physiological mechanisms in tumorigenesis process.
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Zhang H, Li H, Yu H. Analysis of the role of rs2031920 and rs3813867 polymorphisms within the cytochrome P450 2E1 gene in the risk of squamous cell carcinoma. Cancer Cell Int 2018; 18:67. [PMID: 29743817 PMCID: PMC5930765 DOI: 10.1186/s12935-018-0561-8] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/14/2018] [Accepted: 04/19/2018] [Indexed: 11/12/2022] Open
Abstract
Background To explore the genetic effect of rs2031920 and rs3813867 polymorphisms within the cytochrome P450 2E1 (CYP2E1) gene on the risk of squamous cell carcinoma (SCC), a meta-analysis was performed. Methods The eligible case–control studies were obtained by database searching and screening, and the specific statistical analysis was performed with STATA 12.0 software. Results After the process of database searching and screening, a total of 32 case–control studies with 7435 cases and 10,466 controls were ultimately included in our meta-analysis. With regard to the rs2031920 C/T polymorphism, in comparison to controls, a reduced risk in cases of esophageal squamous cell carcinoma (ESCC) was detected for the models of allele T vs. allele C [P = 0.025, odds ratio (OR) = 0.67], carrier T vs. carrier C (P = 0.014, OR = 0.70), TT vs. CC (P = 0.029, OR = 0.65), CT vs. CC (P = 0.040, OR = 0.56), CT + TT vs. CC (P = 0.035, OR = 0.58). Similarly, a decreased SCC risk was observed for the rs3813867 G/C polymorphism in the allele, carrier, homozygote, dominant, and recessive models of overall SCC meta-analysis and “ESCC” subgroup analysis (all P < 0.05, OR < 1) and in all genetic models of “Asian” and “population-based control (PB)” subgroup analysis (all P < 0.05, OR < 1). Additionally, for the rs2031920/rs3813867 haplotype, a decreased SCC risk was also detected in the overall SCC meta-analysis under the allele, carrier, homozygote and dominant model (all P < 0.05, OR < 1) and the subgroup analysis of “PB” under the allele, carrier, and dominant models (all P < 0.05, OR < 1). Conclusions Our meta-analysis supports the “T” allele carrier of the CYP2E1 rs2031920 C/T polymorphism and “C” allele carrier of the rs3813867 G/C polymorphism as protective factors for ESCC patients, especially in Asian populations.
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Affiliation(s)
- Hai Zhang
- Department of Otorhinolaryngology Head and Neck Surgery, Tianjin Huanhu Hospital, No 6, Ji Zhao Road, Jinnan District, Tianjin, 300060 People's Republic of China
| | - Haiyan Li
- Department of Otorhinolaryngology Head and Neck Surgery, Tianjin Huanhu Hospital, No 6, Ji Zhao Road, Jinnan District, Tianjin, 300060 People's Republic of China
| | - Huanxin Yu
- Department of Otorhinolaryngology Head and Neck Surgery, Tianjin Huanhu Hospital, No 6, Ji Zhao Road, Jinnan District, Tianjin, 300060 People's Republic of China
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Marques D, Ferreira-Costa LR, Ferreira-Costa LL, Correa RDS, Borges AMP, Ito FR, Ramos CCDO, Bortolin RH, Luchessi AD, Ribeiro-dos-Santos Â, Santos S, Silbiger VN. Association of insertion-deletions polymorphisms with colorectal cancer risk and clinical features. World J Gastroenterol 2017; 23:6854-6867. [PMID: 29085228 PMCID: PMC5645618 DOI: 10.3748/wjg.v23.i37.6854] [Citation(s) in RCA: 20] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/17/2017] [Revised: 06/24/2017] [Accepted: 08/15/2017] [Indexed: 02/06/2023] Open
Abstract
AIM To investigate the association between 16 insertion-deletions (INDEL) polymorphisms, colorectal cancer (CRC) risk and clinical features in an admixed population.
METHODS One hundred and forty patients with CRC and 140 cancer-free subjects were examined. Genomic DNA was extracted from peripheral blood samples. Polymorphisms and genomic ancestry distribution were assayed by Multiplex-PCR reaction, separated by capillary electrophoresis on the ABI 3130 Genetic Analyzer instrument and analyzed on GeneMapper ID v3.2. Clinicopathological data were obtained by consulting the patients’ clinical charts, intra-operative documentation, and pathology scoring.
RESULTS Logistic regression analysis showed that polymorphism variations in IL4 gene was associated with increased CRC risk, while TYMS and UCP2 genes were associated with decreased risk. Reference to anatomical localization of tumor Del allele of NFKB1 and CASP8 were associated with more colon related incidents than rectosigmoid. In relation to the INDEL association with tumor node metastasis (TNM) stage risk, the Ins alleles of ACE, HLAG and TP53 (6 bp INDEL) were associated with higher TNM stage. Furthermore, regarding INDEL association with relapse risk, the Ins alleles of ACE, HLAG, and UGT1A1 were associated with early relapse risk, as well as the Del allele of TYMS. Regarding INDEL association with death risk before 10 years, the Ins allele of SGSM3 and UGT1A1 were associated with death risk.
CONCLUSION The INDEL variations in ACE, UCP2, TYMS, IL4, NFKB1, CASP8, TP53, HLAG, UGT1A1, and SGSM3 were associated with CRC risk and clinical features in an admixed population. These data suggest that this cancer panel might be useful as a complementary tool for better clinical management, and more studies need to be conducted to confirm these findings.
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Affiliation(s)
- Diego Marques
- Laboratório de Bioanálise e Biotecnologia Molecular, Universidade Federal do Rio Grande do Norte, Natal 59012-570, Rio Grande do Norte, Brazil
- Programa de Pós-graduação em Ciências Farmacêutica, Universidade Federal do Rio Grande do Norte, Natal 59012-570, Rio Grande do Norte, Brazil
- Laboratório de Genética Humana e Médica, Universidade Federal do Pará, Belém 66055-080, Pará, Brazil
| | - Layse Raynara Ferreira-Costa
- Laboratório de Bioanálise e Biotecnologia Molecular, Universidade Federal do Rio Grande do Norte, Natal 59012-570, Rio Grande do Norte, Brazil
| | - Lorenna Larissa Ferreira-Costa
- Laboratório de Bioanálise e Biotecnologia Molecular, Universidade Federal do Rio Grande do Norte, Natal 59012-570, Rio Grande do Norte, Brazil
| | - Romualdo da Silva Correa
- Departamento de Cirurgia Oncológica, Liga Norte Riograndense Contra o Câncer, Natal 59040-000, Rio Grande do Norte, Brazil
| | - Aline Maciel Pinheiro Borges
- Departamento de Cirurgia Oncológica, Liga Norte Riograndense Contra o Câncer, Natal 59040-000, Rio Grande do Norte, Brazil
| | - Fernanda Ribeiro Ito
- Departamento de Cirurgia Oncológica, Liga Norte Riograndense Contra o Câncer, Natal 59040-000, Rio Grande do Norte, Brazil
| | - Carlos Cesar de Oliveira Ramos
- Laboratório de Patologia e Citopatologia, Liga Norte Riograndense Contra o Câncer, Natal 59040-000, Rio Grande do Norte, Brazil
| | - Raul Hernandes Bortolin
- Laboratório de Bioanálise e Biotecnologia Molecular, Universidade Federal do Rio Grande do Norte, Natal 59012-570, Rio Grande do Norte, Brazil
- Programa de Pós-graduação em Ciências Farmacêutica, Universidade Federal do Rio Grande do Norte, Natal 59012-570, Rio Grande do Norte, Brazil
| | - André Ducati Luchessi
- Laboratório de Bioanálise e Biotecnologia Molecular, Universidade Federal do Rio Grande do Norte, Natal 59012-570, Rio Grande do Norte, Brazil
- Departamento de Análises Clínicas e Toxicológicas, Universidade Federal do Rio Grande do Norte, Natal 59012-570, Rio Grande do Norte, Brazil
- Programa de Pós-graduação em Ciências Farmacêutica, Universidade Federal do Rio Grande do Norte, Natal 59012-570, Rio Grande do Norte, Brazil
| | - Ândrea Ribeiro-dos-Santos
- Laboratório de Genética Humana e Médica, Universidade Federal do Pará, Belém 66055-080, Pará, Brazil
- Núcleo de Pesquisas em Oncologia, Universidade Federal do Pará, Belém 66073-005, Pará, Brazil
| | - Sidney Santos
- Laboratório de Genética Humana e Médica, Universidade Federal do Pará, Belém 66055-080, Pará, Brazil
- Núcleo de Pesquisas em Oncologia, Universidade Federal do Pará, Belém 66073-005, Pará, Brazil
| | - Vivian Nogueira Silbiger
- Laboratório de Bioanálise e Biotecnologia Molecular, Universidade Federal do Rio Grande do Norte, Natal 59012-570, Rio Grande do Norte, Brazil
- Departamento de Análises Clínicas e Toxicológicas, Universidade Federal do Rio Grande do Norte, Natal 59012-570, Rio Grande do Norte, Brazil
- Programa de Pós-graduação em Ciências Farmacêutica, Universidade Federal do Rio Grande do Norte, Natal 59012-570, Rio Grande do Norte, Brazil
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Abstract
In first part of this study, a systematic review was designed to explore the involvement of CYP1A1 and GSTP1 genes in breast cancerogenesis. Based on systematic review, we designed a study to screen CYP1A1 and GSTP1 genes for mutation and their possible association with breast carcinogenesis. A total of 400 individuals were collected and analyzed by PCR-SSCP. After sequence analysis of coding region of CYP1A1 we identified eleven mutations in different exons of respective gene. Among these eleven mutations, ~3 folds increased breast cancer risk was found associated with Asp82Glu mutation (OR 2.99; 95% CI 1.26-7.09), with Ser83Thr mutation (OR 2.99; 95% CI 1.26-7.09) and with Glu86Ala mutation (OR 3.18; 95% CI 1.27-7.93) in cancer patients compared to controls. Furthermore, ~4 folds increase in breast cancer risk was found associated with Asp347Glu, Phe398Tyr and 5178delT mutations (OR 3.92; 95% CI 1.35-11.3) in patients compared to controls. The sequence analysis of GSTP1 resulted in identification of total five mutations. Among these five mutations, ~3 folds increase in breast cancer risk was observed associated with 1860G>A mutation, with 1861-1876delCAGCCCTCTGGAGTGG mutation (OR 2.70; 95% CI 1.10-6.62) and with 1861C>A mutation (OR 2.97; 95% CI 1.01-8.45) in cancer patients compared to controls. Furthermore, ~5 folds increase in breast cancer risk was associated with 1883G>T mutation (OR 4.75; 95% CI 1.46-15.3) and ~6 folds increase in breast cancer risk was found associated with Iso105Val mutation (OR 6.43; 95% CI 1.41-29.3) in cancer patients compared to controls. Our finding, based on systematic review and experimental data suggest that the polymorphic CYP1A1 and GSTP1 genes may contribute to risk of developing breast cancer.
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Fernandes GMM, Russo A, Proença MA, Gazola NF, Rodrigues GH, Biselli-Chicote PM, Silva AE, Netinho JG, Pavarino &EC, Goloni-Bertollo EM. CYP1A1, CYP2E1 and EPHX1 polymorphisms in sporadic colorectal neoplasms. World J Gastroenterol 2016; 22:9974-9983. [PMID: 28018104 PMCID: PMC5143764 DOI: 10.3748/wjg.v22.i45.9974] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/10/2016] [Revised: 10/08/2016] [Accepted: 11/16/2016] [Indexed: 02/06/2023] Open
Abstract
AIM To investigate the contribution of polymorphisms in the CYP1A1, CYP2E1 and EPHX1 genes on sporadic colorectal cancer (SCRC) risk.
METHODS Six hundred forty-one individuals (227 patients with SCRC and 400 controls) were enrolled in the study. The variables analyzed were age, gender, tobacco and alcohol consumption, and clinical and histopathological tumor parameters. The CYP1A1*2A, CYP1A1*2C CYP2E1*5B and CYP2E1*6 polymorphisms were analyzed by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). The EPHX1 Tyr113His, EPHX1 His139Arg and CYP1A1*2C polymorphisms were detected by real-time PCR. Chi-squared test and binary logistic regression were used in the statistical analysis. Haplotype analysis was conducted using the Haploview program, version 2.05.
RESULTS Age over 62 years was a risk factor for SCRC development (OR = 7.54, 95%CI: 4.94-11.50, P < 0.01). Male individuals were less susceptible to SCRC (OR = 0.55, 95%CI: 0.35-0.85, P < 0.01). The CYP2E1*5B polymorphism was associated with SCRC in the codominant (heterozygous genotype: OR = 2.66, 95%CI: 1.64-4.32, P < 0.01), dominant (OR = 2.82, 95%CI: 1.74-4.55, P < 0.01), overdominant (OR = 2.58, 95%CI: 1.59-4.19, P < 0.01), and log-additive models (OR = 2.84, 95%CI: 1.78-4.52, P < 0.01). The CYP2E1*6 polymorphism was associated with an increased SCRC risk in codominant (heterozygous genotype: OR = 2.81, 95%CI: 1.84-4.28, P < 0.01; homozygous polymorphic: OR = 7.32, 95%CI: 1.85-28.96, P < 0.01), dominant (OR = 2.97, 95%CI: 1.97-4.50, P < 0.01), recessive (OR = 5.26, 95%CI: 1.35-20.50, P = 0.016), overdominant (OR = 2.64, 95%CI: 1.74-4.01, P < 0.01), and log-additive models (OR = 2.78, 95%CI: 1.91-4.06, P < 0.01). The haplotype formed by the minor alleles of the CYP2E1*5B (C) and CYP2E1*6 (A) polymorphisms was associated with SCRC (P = 0.002). However, the CYP1A1*2A, CYP1A1*2C, EPHX1 Tyr113His and EPHX1 His139Arg polymorphisms were not associated with SCRC.
CONCLUSION In conclusion, the results demonstrated that CYP2E1*5B and CYP2E1*6 minor alleles play a role in the development of SCRC.
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Zhuo X, Song J, Liao J, Zhou W, Ye H, Li Q, Xiang Z, Zhang X. Does CYP2E1 RsaI/PstI polymorphism confer head and neck carcinoma susceptibility?: A meta-analysis based on 43 studies. Medicine (Baltimore) 2016; 95:e5156. [PMID: 27787372 PMCID: PMC5089101 DOI: 10.1097/md.0000000000005156] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/14/2022] Open
Abstract
BACKGROUND Previous reports showed that CYP2E1 RsaI/PstI polymorphism may be a risk factor for cancers. Published meta-analyses in 2010 and 2011, respectively, on the relationship of CYP2E1 RsaI/PstI polymorphisms with the susceptibility to head and neck carcinoma (HNC) have generated inconsistent results. Thus, this study aimed to conduct an updated meta-analysis involving published studies up to Nov 2015 to get a more confidential result. METHODS Eligible studies up to Nov 2015 were retrieved and screened. Data were extracted and a quantitative meta-analysis was conducted. Subgroup analyses on ethnicity, source of controls, sample size, genotyping method, smoking status, and drinking status were also performed. RESULTS Forty-one publications including a total of 43 case-control studies were selected for analysis. The overall data under a homozygote comparison model indicated a significant association of CYP2E1 RsaI/PstI polymorphisms with HNC risk (c2c2 vs c1c1: odds ratio [OR] = 1.97; 95% confidence interval [CI] = 1.53-2.53). Similar results were observed in the Asian subgroup (c2c2 vs c1c1: OR = 1.98; 95%CI = 1.51-2.60; c2 vs c1: OR = 1.20; 95%CI = 1.03-1.39) and mixed population (c2 vs c1: OR = 1.41; 95%CI = 1.06-1.86) when the data were stratified by ethnicities. Interestingly, increased cancer risk only was shown among never-smokers (c2c2+c1c2 vs c1c1: OR = 1.44; 95%CI = 1.05-1.98) but not ever-smokers. CONCLUSION CYP2E1 RsaI/PstI polymorphisms may modify the susceptibility to HNC, particularly among Asians, mixed population, and never-smokers. Future large and well-designed studies are needed to verify this conclusion.
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Affiliation(s)
- Xianlu Zhuo
- Department of Otolaryngology, Southwest Hospital, Third Military Medical University, Chongqing
- Affiliated Hospital of Guiyang Medical University, Guiyang
- Post-doctoral Scientific Research Station, Chongqing Cancer Institute, Chongqing, China
- Correspondence: Xianlu Zhuo and Xueyuan Zhang, Department of Otolaryngology, Southwest Hospital, Third Military Medical University, Chongqing, China (e-mails: [Xianlu Zhuo]; [Xueyuan Zhang])
| | - Jue Song
- Affiliated Hospital of Guiyang Medical University, Guiyang
| | - Jian Liao
- Affiliated Hospital of Guiyang Medical University, Guiyang
| | - Wei Zhou
- Post-doctoral Scientific Research Station, Chongqing Cancer Institute, Chongqing, China
| | - Huiping Ye
- Affiliated Hospital of Guiyang Medical University, Guiyang
| | - Qi Li
- Department of Otolaryngology, Southwest Hospital, Third Military Medical University, Chongqing
| | - Zhaolan Xiang
- Department of Otolaryngology, Southwest Hospital, Third Military Medical University, Chongqing
| | - Xueyuan Zhang
- Department of Otolaryngology, Southwest Hospital, Third Military Medical University, Chongqing
- Correspondence: Xianlu Zhuo and Xueyuan Zhang, Department of Otolaryngology, Southwest Hospital, Third Military Medical University, Chongqing, China (e-mails: [Xianlu Zhuo]; [Xueyuan Zhang])
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Singh SA, Choudhury JH, Kapfo W, Kundu S, Dhar B, Laskar S, Das R, Kumar M, Ghosh SK. Influence of the CYP1A1 T3801C Polymorphism on Tobacco and Alcohol-Associated Head and Neck Cancer Susceptibility in Northeast India. Asian Pac J Cancer Prev 2016; 16:6953-61. [PMID: 26514474 DOI: 10.7314/apjcp.2015.16.16.6953] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/10/2022] Open
Abstract
BACKGROUND Tobacco and alcohol contain or may generate carcinogenic compounds related to cancers. CYP1A1 enzymes act upon these carcinogens before elimination from the body. The aim of this study was to investigate whether CYP1A1 T3801C polymorphism modulates the relationship between tobacco and alcohol- associated head and neck cancer (HNC) susceptibility among the northeast Indian population. MATERIALS AND METHODS One hundred and seventy histologically confirmed HNC cases and 230 controls were included within the study. The CYP1A1 T3801C polymorphism was determined using PCR-RFLP, and the results were confirmed by DNA sequencing. Logistic regression (LR) and multifactor dimensionality reduction (MDR) approaches were applied for statistical analysis. RESULTS The CYP1A1 CC genotype was significantly associated with HNC risk (P=0.045). A significantly increased risk of HNC (OR=6.09; P<0.0001) was observed in individuals with combined habits of smoking, alcohol drinking and tobacco-betel quid chewing. Further, gene-environment interactions revealed enhanced risks of HNC among smokers, alcohol drinkers and tobacco-betel quid chewers carrying CYP1A1 TC or CC genotypes. The highest risk of HNC was observed among smokers (OR=7.55; P=0.009) and chewers (OR=10.8; P<0.0001) carrying the CYP1A1 CC genotype. In MDR analysis, the best model for HNC risk was the three-factor model combination of smoking, tobacco-betel quid chewing and the CYP1A1 variant genotype (CVC=99/100; TBA=0.605; P<0.0001); whereas interaction entropy graphs showed synergistic interaction between tobacco habits and CYP1A1. CONCLUSIONS Our results confirm that the CYP1A1 T3801C polymorphism modifies the risk of HNC and further demonstrated importance of gene-environment interaction.
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Affiliation(s)
- Seram Anil Singh
- Molecular Medicine Laboratory, Department of Biotechnology, Assam University, Silchar, Assam, India E-mail :
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Xie S, Luo C, Shan X, Zhao S, He J, Cai Z. CYP1A1 MspI polymorphism and the risk of oral squamous cell carcinoma: Evidence from a meta-analysis. Mol Clin Oncol 2016; 4:660-666. [PMID: 27073686 DOI: 10.3892/mco.2016.768] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/05/2014] [Accepted: 01/29/2016] [Indexed: 12/20/2022] Open
Abstract
Numerous case-control studies have investigated whether the CYP1A1 gene polymorphism is involved in the occurrence of oral squamous cell carcinoma (OSCC); however, the conclusions are inconsistent. In order to further explore the correlation and obtain a strong conclusion, a meta-analysis was performed to systematically assess the association between the CYP1A1 MspI polymorphism and risk of OSCC. In the present meta-analysis, the odds ratios (ORs) and the corresponding 95% confidence intervals (CIs) were used to assess the association. The statistical analyses were performed with STATA 11.0 software. The heterogeneity was assessed by Q test and I2test. The final analysis included 10 studies of 1,505 cases and 1,967 controls. The overall results suggested that the CYP1A1 MspI polymorphism was significantly associated with an increased risk of OSCC (CC+TC vs. TT: OR, 1.31; 95% CI, 1.01-1.70; P=0.043; CC vs. TC+TT: OR, 2.38; 95% CI, 1.58-3.58; P<0.001; CC vs. TT: OR, 2.52; 95% CI, 1.60-3.96; P<0.001; and C vs. T: OR, 1.45; 95% CI, 1.15-1.83; P<0.001). In a stratified analysis by ethnicity, a statistically significant correlation existed in the Asian population, but not mixed-race and Caucasian populations. In conclusion, despite several limitations, the present meta-analysis established that the CYP1A1 MspI polymorphism may be a risk factor for OSCC, particularly among the Asian population.
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Affiliation(s)
- Shang Xie
- Department of Oral and Maxillofacial Surgery, Peking University School and Hospital of Stomatology, Beijing 100081, P.R. China
| | - Chongdai Luo
- Guanghua School and Hospital of Stomatology, Sun Yat-Sen University, Guangzhou, Guangdong 510055, P.R. China
| | - Xiaofeng Shan
- Department of Oral and Maxillofacial Surgery, Peking University School and Hospital of Stomatology, Beijing 100081, P.R. China
| | - Shushan Zhao
- Department of Orthopaedic Surgery, Xiangya Hospital, Changsha, Hunan 410008, P.R. China
| | - Jing He
- State Key Laboratory of Oncology in South China, Department of Experimental Research, Collaborative Innovation Center for Cancer Medicine, Sun Yat-Sen University Cancer Center, Guangzhou, Guangdong 510060, P.R. China
| | - Zhigang Cai
- Department of Oral and Maxillofacial Surgery, Peking University School and Hospital of Stomatology, Beijing 100081, P.R. China
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Abstract
Cytochrome 450 (CYP450) designates a group of enzymes abundant in smooth endoplasmic reticulum of hepatocytes and epithelial cells of small intestines. The main function of CYP450 is oxidative catalysis of various endogenous and exogenous substances. CYP450 are implicated in phase I metabolism of 80% of drugs currently in use, including anticancer drugs. They are also involved in synthesis of various hormones and influence hormone-related cancers. CYP450 genes are highly polymorphic and their variants play an important role in cancer risk and treatment. Association studies and meta-analyses have been performed to decipher the role of CYP450 polymorphisms in cancer susceptibility. Cancer treatment involves multimodal therapies and evaluation of CYP450 polymorphisms is necessary for pharmacogenetic assessment of anticancer therapy outcomes. In addition, CYP450 inhibitors are being evaluated for improved pharmacokinetics and oral formulation of several anticancer drugs.
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Jin J, Lin F, Liao S, Bao Q, Ni L. Effects of SNPs (CYP1B1*2 G355T, CYP1B1*3 C4326G, and CYP2E1*5 G-1293C), smoking, and drinking on susceptibility to laryngeal cancer among Han Chinese. PLoS One 2014; 9:e106580. [PMID: 25299224 PMCID: PMC4191961 DOI: 10.1371/journal.pone.0106580] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/27/2014] [Accepted: 08/07/2014] [Indexed: 12/25/2022] Open
Abstract
Purpose This study was conducted to explore the effects of genetic polymorphisms (CYP1B1*2 G355T, CYP1B1*3 C4326G, and CYP2E1*5 G-1293C) and environmental factors (smoking and drinking) on susceptibility to laryngeal cancer in a Han Chinese study group. Methods This case-control study included 552 Han Chinese patients diagnosed with laryngeal cancer and 666 healthy control subjects of the same ethnicity, similar age, and gender. Genetic polymorphisms were examined using multi-PCR and Matrix Assisted Laser Desorption Ionization - Time of Flight (MALDI-TOF MS) methodology. The association of these genetic and environmental factors with susceptibility to laryngeal cancer was evaluated using a statistical approach. Results The frequencies of all three polymorphisms in the patient cohort were significantly different from those in the control cohort. Compared to the control cohort, carriers of variant alleles of CYP1B1*2 355T and CYP2E1*5 -1293C showed a higher risk for developing laryngeal cancer (for CYP1B1*2 355T, adjusted OR = 2.657, P <0.001; for CYP2E1*5 -1293C, adjusted OR = 1.938, P <0.001), while carriers of mutation allele CYP1B1*3 4326G showed a lower risk (adjusted OR = 0.562, P <0.001). Joint effects of these polymorphisms were observed. When compared to haplotype G355C4326G−1293, haplotypes T355C4326G−1293 (adjusted OR = 1.809, P <0.001), G355C4326C−1293 (adjusted OR = 1.644, P = 0.044), and T355C4326C−1293 (adjusted OR = 3.104, P <0.001) were associated with a significantly higher laryngeal cancer risk. The adjusted ORs for non-smokers, non-drinkers, smokers, and drinkers with the GT/TT genotype at CYP1B1*2 G355T were 2.190 (P = 0.006), 2.008 (P = 0.001), 5.875 (P <0.001), and 4.518 (P <0.001), respectively. Conclusions CYP1B1*2 355T and CYP2E1*5 -1293C are associated with an increased laryngeal cancer risk, while CYP1B1*3 4326G is associated with a decreased risk. These polymorphisms showed joint effects on laryngeal cancer risk. Smoking and drinking showed collaborative effects with two high risk alleles (CYP1B1*2 355T and CYP1B1*3 4326G) for promoting laryngeal cancer risk.
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Affiliation(s)
- Jianhua Jin
- School of Basic Medicine, Wenzhou Medical University, Wenzhou, China
| | - Faming Lin
- The Second Affiliated Hospital of Wenzhou medical University, Wenzhou, China
| | - Shiyu Liao
- The Second Affiliated Hospital of Wenzhou medical University, Wenzhou, China
| | - Qiyu Bao
- Institute of Biomedical Informatics/Zhejiang Provincial Key Laboratory of Medical Genetics, School of Life Sciences, Wenzhou Medical University, Wenzhou, China
| | - Liyan Ni
- The Second Affiliated Hospital of Wenzhou medical University, Wenzhou, China
- * E-mail:
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Han J, Wang L, Yang Y, Zhang J. Meta-analyses of the effect of CYP1A1 and CYP2D6 polymorphisms on the risk of head and neck squamous cell carcinoma. Oncol Res Treat 2014; 37:406-11. [PMID: 25138301 DOI: 10.1159/000363428] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/09/2013] [Accepted: 04/04/2014] [Indexed: 11/19/2022]
Abstract
BACKGROUND CYP1A1 and CYP2D6 are important genes encoding enzymes involved in the metabolism of toxic chemicals and carcinogens. However, inconclusive results for the association between CYP1A1 and CYP2D6 polymorphisms and the risk of head and neck squamous cell carcinoma (HNSCC) have been reported. We conducted a meta-analysis to evaluate the association of CYP1A1 and CYP2D6 polymorphisms with the risk of HNSCC. METHODS A database search yielded 19 relevant studies. 3 polymorphisms were included in the meta-analysis: CYP1A1, CYP2D6*4 and CYP2D6*10. Random or fixed effect models were used in the analysis. RESULTS The CYP1A1 polymorphism was associated with HNSCC (for m1m1 vs. m1m2: odds ratio (OR) = 1.26, 95% confidence interval (CI) = 1.030-1.542, pheterogeneity = 0.025; for the recessive model: OR = 1.316, 95% CI = 1.065-1.625, pheterogeneity = 0.001). The analysis showed evidence for association between the CYP2D6*4 polymorphism and HNSCC in Asian populations; however, negative results were also observed in other models. A significant association was also observed between CYP2D6*10 polymorphism and HNSCC risk. CONCLUSIONS The current study demonstrates that the CYP1A1 and CYP2D6 polymorphisms are associated with susceptibility to both development and progression of HNSCC.
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Affiliation(s)
- Jiming Han
- Department of Nursing Faculty, Medical College of Yan'an University, Shanxi, China
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Association between the CYP1A1 T3801C polymorphism and risk of cancer: Evidence from 268 case–control studies. Gene 2014. [PMID: 24498651 DOI: 10.1016/j.gene.2013.10.025] [Citation(s) in RCA: 19] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
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Khlifi R, Messaoud O, Rebai A, Hamza-Chaffai A. Polymorphisms in the human cytochrome P450 and arylamine N-acetyltransferase: susceptibility to head and neck cancers. BIOMED RESEARCH INTERNATIONAL 2013; 2013:582768. [PMID: 24151610 PMCID: PMC3787584 DOI: 10.1155/2013/582768] [Citation(s) in RCA: 25] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 04/19/2013] [Revised: 06/25/2013] [Accepted: 07/24/2013] [Indexed: 12/12/2022]
Abstract
The occurrence of head and neck cancer (HNC) is associated with smoking and alcohol drinking. Tobacco smoking exposes smokers to a series of carcinogenic chemicals. Cytochrome P450 enzymes (CYP450s), such as CYP1A1, CYP1B1, and CYP2D6, usually metabolize carcinogens to their inactive derivatives, but they occasionally convert the chemicals to more potent carcinogens. In addition, via CYP450 (CYP2E1) oxidase, alcohol is metabolized to acetaldehyde, a highly toxic compound, which plays an important role in carcinogenesis. Furthermore, two N-acetyltransferase isozymes (NATs), NAT1 and NAT2, are polymorphic and catalyze both N-acetylation and O-acetylation of aromatic and heterocyclic amine carcinogens. Genetic polymorphisms are associated with a number of enzymes involved in the metabolism of carcinogens important in the induction of HNC. It has been suggested that such polymorphisms may be linked to cancer susceptibility. In this paper, we select four cytochrome P450 enzymes (CYP1A1, CYP1BA1, CYP2D6, and CYP2E1), and two N-acetyltransferase isozymes (NAT1 and NAT2) in order to summarize and analyze findings from the literature related to HNC risk by focusing on (i) the interaction between these genes and the environment, (ii) the impact of genetic defect on protein activity and/or expression, and (iii) the eventual involvement of race in such associations.
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Affiliation(s)
- Rim Khlifi
- Research Unit on Toxicology and Environment, Sfax University, 3018 Sfax, Tunisia
- Bioinformatics Unit, Centre of Biotechnology of Sfax, Sfax University, 3018 Sfax, Tunisia
| | - Olfa Messaoud
- Biomedical Genomics and Oncogenetics Laboratory LR11IPT05, University of Tunis El Manar, 1002 Tunis, Tunisia
| | - Ahmed Rebai
- Bioinformatics Unit, Centre of Biotechnology of Sfax, Sfax University, 3018 Sfax, Tunisia
| | - Amel Hamza-Chaffai
- Research Unit on Toxicology and Environment, Sfax University, 3018 Sfax, Tunisia
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Russo A, Francelin PR, Galbiatti ALS, Raposo LS, Maníglia JV, Pavarino ÉC, Goloni-Bertollo EM. Association between GSTP1, GSTM1 and GSTT1 polymorphisms involved in xenobiotic metabolism and head and neck cancer development. Mol Biol Rep 2013; 40:4181-8. [DOI: 10.1007/s11033-013-2499-1] [Citation(s) in RCA: 10] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/26/2012] [Accepted: 04/26/2013] [Indexed: 12/15/2022]
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Liu L, Wu G, Xue F, Li Y, Shi J, Han J, Zhang X, Na Y, Zhang H, Tang X, Pu H, Yuan Q, Zhang L, Yang M. Functional CYP1A1 genetic variants, alone and in combination with smoking, contribute to development of head and neck cancers. Eur J Cancer 2013; 49:2143-51. [PMID: 23462525 DOI: 10.1016/j.ejca.2013.01.028] [Citation(s) in RCA: 25] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/28/2012] [Revised: 01/18/2013] [Accepted: 01/28/2013] [Indexed: 02/06/2023]
Abstract
CYP1A1 plays an essential role in pathogenesis of head and neck cancers. Functional CYP1A1 Ile462Val and MspI single nucleotide polymorphisms (SNP) are considered to have significant effects on risk of head and neck cancers. Several case-control studies have examined how these genetic polymorphisms are involved in development of this group of malignancies, but the conclusions are inconsistent. Therefore, we conducted this meta-analysis to systematically examine the associations between these functional genetic variants and head and neck cancer risk. A total of 28 studies are eligible for CYP1A1 Ile462Val SNP (4639 patients and 4701 controls), and 22 studies for MspI SNP (4168 patients and 4638 controls). Pooled odds ratios (ORs) and the 95% confidence interval (95% CI) were appropriately calculated using either fixed-effect model or random-effect model. There was no association between Ile462Val polymorphism and head and neck cancer risk (OR = 1.23, 95% CI = 0.99-1.53, P = 0.062). However, in a stratified analysis, a statistically significant correlation between this SNP and pharyngeal cancer risk was observed (OR = 1.76, 95% CI = 1.32-2.33, P < 0.001). For MspI SNP, our data indicated that carriers of TC and CC genotypes had a 34% increased risk to develop head and neck cancers compared to TT carriers (95% CI = 1.15-1.57, P < 0.001). This effect was even more pronounced in smokers (OR = 2.98, 95% CI = 1.69-5.26, P < 0.001), demonstrating that gene-smoking interaction intensifying carcinogenesis may exist. These findings reveal that the functional CYP1A1 MspI genetic variant, alone and in combination with smoking, plays a more important role in pathogenesis of head and neck cancers.
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Affiliation(s)
- Li Liu
- State Key Laboratory of Chemical Resource Engineering, College of Life Science and Technology, Beijing University of Chemical Technology, Beijing, China
| | - Gang Wu
- Liaoning International Travel Healthcare Center, Dalian, Liaoning Province, China
| | - Fang Xue
- Liaoning International Travel Healthcare Center, Dalian, Liaoning Province, China
| | - Yunfeng Li
- Liaoning International Travel Healthcare Center, Dalian, Liaoning Province, China
| | - Juan Shi
- State Key Laboratory of Chemical Resource Engineering, College of Life Science and Technology, Beijing University of Chemical Technology, Beijing, China
| | - Jianjun Han
- Department of Intervention Surgery, Shandong Cancer Hospital, Shandong Academy of Medical Sciences, Jinan, Shandong Province, China
| | - Xiaojiao Zhang
- State Key Laboratory of Chemical Resource Engineering, College of Life Science and Technology, Beijing University of Chemical Technology, Beijing, China
| | - Yan Na
- State Key Laboratory of Chemical Resource Engineering, College of Life Science and Technology, Beijing University of Chemical Technology, Beijing, China
| | - Huaijin Zhang
- State Key Laboratory of Chemical Resource Engineering, College of Life Science and Technology, Beijing University of Chemical Technology, Beijing, China
| | - Xiaohu Tang
- State Key Laboratory of Chemical Resource Engineering, College of Life Science and Technology, Beijing University of Chemical Technology, Beijing, China
| | - Honglei Pu
- State Key Laboratory of Chemical Resource Engineering, College of Life Science and Technology, Beijing University of Chemical Technology, Beijing, China
| | - Qipeng Yuan
- State Key Laboratory of Chemical Resource Engineering, College of Life Science and Technology, Beijing University of Chemical Technology, Beijing, China
| | - Li Zhang
- Department of Oncology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei Province, China
| | - Ming Yang
- State Key Laboratory of Chemical Resource Engineering, College of Life Science and Technology, Beijing University of Chemical Technology, Beijing, China.
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