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Kim E, Chen C, Chu MJ, Hamstra MF, Bentley WE, Payne GF. Proline-Selective Electrochemiluminescence Detecting a Single Amino Acid Variation Between A1 and A2 β-Casein Containing Milks. ADVANCED SCIENCE (WEINHEIM, BADEN-WURTTEMBERG, GERMANY) 2025; 12:e2411956. [PMID: 39644502 PMCID: PMC11792022 DOI: 10.1002/advs.202411956] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 09/26/2024] [Revised: 11/05/2024] [Indexed: 12/09/2024]
Abstract
The proline amino acid and prolyl residues of peptides/proteins confer unique biological and biochemical properties that motivates the development of proline-selective analysis. The study focuses on one specific class of problem, the detection of single amino acid variants involving proline, and reports a Pro-selective electrochemiluminescence (ECL) method. To develop this method, the A1-/A2- variants of milk's β-casein protein are investigated because it is a well-established example and abundant samples are readily available. Specifically, β-casein has 209 amino acids with 34 (or 35) proline residues: the A1-variant has a Pro-to-His substitution at position 67 (relative to the A2 variant). The study shows that proline's strong luminescence allows the generic discrimination of: Pro from other amino acids; an A2-oligopeptide from an A1-oligopeptide; the A2-β-casein variant from the A1-variant; and commercially-available A2 milks from A1-containing regular milks. The evidence indicates that luminescence depends on proline content and accessibility, as well as signal quenching. Compared to conventional immunoassays, the ECL method is simple, rapid, and inexpensive. Further, the ECL-method is Pro-selective (vs molecularly-selective like typical immunoassays) which should make it broadly useful for studying the role of proline in biology and especially useful for tracking the digestion of proline-rich proteins in the diet.
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Affiliation(s)
- Eunkyoung Kim
- Institute for Bioscience and Biotechnology ResearchUniversity of MarylandCollege ParkMaryland20742USA
- Robert E. Fischell Institute for Biomedical DevicesUniversity of MarylandCollege ParkMaryland20742USA
| | - Chen‐Yu Chen
- Institute for Bioscience and Biotechnology ResearchUniversity of MarylandCollege ParkMaryland20742USA
- Robert E. Fischell Institute for Biomedical DevicesUniversity of MarylandCollege ParkMaryland20742USA
- Fischell Department of BioengineeringUniversity of MarylandCollege ParkMaryland20742USA
| | - Monica J. Chu
- Fischell Department of BioengineeringUniversity of MarylandCollege ParkMaryland20742USA
| | - Mya F. Hamstra
- Fischell Department of BioengineeringUniversity of MarylandCollege ParkMaryland20742USA
| | - William E. Bentley
- Institute for Bioscience and Biotechnology ResearchUniversity of MarylandCollege ParkMaryland20742USA
- Robert E. Fischell Institute for Biomedical DevicesUniversity of MarylandCollege ParkMaryland20742USA
- Fischell Department of BioengineeringUniversity of MarylandCollege ParkMaryland20742USA
| | - Gregory F. Payne
- Institute for Bioscience and Biotechnology ResearchUniversity of MarylandCollege ParkMaryland20742USA
- Robert E. Fischell Institute for Biomedical DevicesUniversity of MarylandCollege ParkMaryland20742USA
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Galíndez MF, Carrica A, Zarate AM, Secchi D, Don J, Barra JL, Brunotto M. DNA repair, NFKβ, and TP53 polymorphisms associated with potentially malignant disorders and oral squamous cell carcinoma in Argentine patients. Oral Surg Oral Med Oral Pathol Oral Radiol 2020; 131:339-346. [PMID: 33309268 DOI: 10.1016/j.oooo.2020.11.004] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/24/2020] [Revised: 10/12/2020] [Accepted: 11/08/2020] [Indexed: 12/13/2022]
Abstract
OBJECTIVE An important strategy in cancer prevention is to identify individual susceptibilities for cancer development through the genomic profile. Developing countries such as Argentina have no data on genetic composition. The aim of this study was to evaluate the single nucleotide polymorphisms of genes related to DNA repair (XCCR3, XPD), cell cycle arrest/apoptosis (TP53), and inflammation (NFKβ) of patients with precancer and oral cancer and to contribute to recognizing potential risk of developing these pathologies, and incorporate the risk patients into a clinical follow-up program in Córdoba, Argentina. STUDY DESIGN A cross-sectional study was performed on 140 patients with oral squamous cell carcinoma (OSCC), oral potentially malignant disorders (OPMDs), and controls. Genotyping of single nucleotide polymorphisms was performed using allele-specific polymerase chain reaction or restriction fragment length polymorphism techniques. The variables were evaluated by bivariate and multivariate statistical methods, with P < .05 statistically significant. RESULTS The multiple correspondence analyses showed that patients with OSCC are clustered with the T allele of XRCC3 T241 M and the C allele of TP53 R72 P, and patients with OPMDs are clustered with the T allele of NFKβ-519. CONCLUSION Our preliminary results showed that the C allele of the Pro72 variant of TP53 was related to OSSC and OPMD, and the T allele of NFKβ-519 is related to OPMDs in Argentine patients.
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Affiliation(s)
- María Fernanda Galíndez
- Universidad Nacional de Córdoba, Facultad de Odontología, Departamento de Patología Bucal, Haya de la Torre S/N, Ciudad Universitaria, Córdoba, Argentina
| | - Andrés Carrica
- Universidad Nacional de Córdoba, Facultad de Odontología, Departamento de Patología Bucal, Haya de la Torre S/N, Ciudad Universitaria, Córdoba, Argentina
| | - Ana María Zarate
- Universidad Nacional de Córdoba, Facultad de Odontología, Departamento de Patología Bucal, Haya de la Torre S/N, Ciudad Universitaria, Córdoba, Argentina
| | - Dante Secchi
- Universidad Nacional de Córdoba, Facultad de Odontología, Departamento de Patología Bucal, Haya de la Torre S/N, Ciudad Universitaria, Córdoba, Argentina
| | - Julieta Don
- Universidad Nacional de Córdoba, Facultad de Odontología, Departamento de Patología Bucal, Haya de la Torre S/N, Ciudad Universitaria, Córdoba, Argentina
| | - José Luis Barra
- Universidad Nacional de Córdoba, Facultad de Ciencias Químicas, CIQUIBIC-CONICET, Haya de la Torre S/N, Ciudad Universitaria, Córdoba, Argentina
| | - Mabel Brunotto
- Universidad Nacional de Córdoba, Facultad de Odontología, Departamento de Patología Bucal, Haya de la Torre S/N, Ciudad Universitaria, Córdoba, Argentina; Instituto de Investigaciones en Ciencias de la Salud, (INICSA-CONICET-UNC), Bv. de la Reforma esq. Enf. Gordillo, Ciudad Universitaria, Córdoba, Argentina.
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Wu MY, Huang SJ, Yang F, Qin XT, Liu D, Ding Y, Yang S, Wang XC. Detection of nasopharyngeal carcinoma susceptibility with single nucleotide polymorphism analysis using next-generation sequencing technology. Oncotarget 2017; 8:52708-52723. [PMID: 28881764 PMCID: PMC5581063 DOI: 10.18632/oncotarget.17085] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/12/2016] [Accepted: 03/17/2017] [Indexed: 01/18/2023] Open
Abstract
Nasopharyngeal carcinoma (NPC) is a head and neck cancer with high incidence in South China and East Asia. To provide a theoretical basis for NPC risk screening and early prevention, we conducted a meta-analysis of relevant literature on the association of single nucleotide polymorphisms (SNP)s with NPC susceptibility. Further, expression of 15 candidate SNPs identified in the meta-analysis was evaluated in a cohort of NPC patients and healthy volunteers using next-generation sequencing technology. Among the 15 SNPs detected in the meta-analysis, miR-146a (rs2910164, C>G), HCG9 (rs3869062, A>G), HCG9 (rs16896923, T>C), MMP2 (rs243865, C>T), GABBR1 (rs2076483, T>C), and TP53 (rs1042522, C>G) were associated with decreased susceptibility to NPC, while GSTM1 (+/DEL), IL-10 (rs1800896, A>G), MDM2 (rs2279744, T>G), MDS1-EVI1 (rs6774494, G>A), XPC (rs2228000, C>T), HLA-F (rs3129055, T>C), SPLUNC1 (rs2752903, T>C; and rs750064, A>G), and GABBR1 (rs29232, G>A) were associated with increased susceptibility to NPC. In our case-control study, an association with increased risk for NPC was found for the AG vs AA genotype in HCG9 (rs3869062, A>G). In addition, heterozygous deletion of the GSTM1 allele was associated with increased susceptibility to NPC, while an SNP in GABBR1 (rs29232, G>A) was associated with decreased risk, and might thus have a protective role on NPC carcinogenesis. This work provides the first comprehensive assessment of SNP expression and its relationship to NPC risk. It suggests the need for well-designed, larger confirmatory studies to validate its findings.
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Affiliation(s)
- Mu-Yun Wu
- Department of Oncology, The First Affiliated Hospital of Guangdong Pharmaceutical University, Guangzhou, China
- Department of Oncology, The Fifth People's Hospital of Wuhu, Wuhu, China
| | - Shu-Jing Huang
- Department of Oncology, The First Affiliated Hospital of Guangdong Pharmaceutical University, Guangzhou, China
| | - Fan Yang
- Department of Oncology, The First Affiliated Hospital of Guangdong Pharmaceutical University, Guangzhou, China
| | - Xin-Tian Qin
- Department of Oncology, The First Affiliated Hospital of Guangdong Pharmaceutical University, Guangzhou, China
| | - Dong Liu
- Department of Oncology, The First Affiliated Hospital of Guangdong Pharmaceutical University, Guangzhou, China
| | - Ying Ding
- Department of Oncology, The First Affiliated Hospital of Guangdong Pharmaceutical University, Guangzhou, China
| | - Shu Yang
- Department of Oncology, The First Affiliated Hospital of Guangdong Pharmaceutical University, Guangzhou, China
| | - Xi-Cheng Wang
- Department of Oncology, The First Affiliated Hospital of Guangdong Pharmaceutical University, Guangzhou, China
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Association of p53 codon72 Arg>Pro polymorphism with susceptibility to nasopharyngeal carcinoma: evidence from a case-control study and meta-analysis. Oncogenesis 2016; 5:e225. [PMID: 27159678 PMCID: PMC4945748 DOI: 10.1038/oncsis.2016.31] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/07/2015] [Revised: 12/24/2016] [Accepted: 01/26/2016] [Indexed: 12/28/2022] Open
Abstract
Tumor suppressor p53 is a critical player in the fight against cancer as it controls the cell cycle check point, apoptotic pathways and genomic stability. It is known to be the most frequently mutated gene in a wide variety of human cancers. Single-nucleotide polymorphism of p53 at codon72 leading to substitution of proline (Pro) in place of arginine (Arg) has been identified as a risk factor for development of many cancers, including nasopharyngeal carcinoma (NPC). However, the association of this polymorphism with NPC across the published literature has shown conflicting results. We aimed to conduct a case–control study for a possible relation of p53 codon72 Arg>Pro polymorphism with NPC risk in underdeveloped states of India, combine the result with previously available records from different databases and perform a meta-analysis to draw a more definitive conclusion. A total of 70 NPC patients and 70 healthy controls were enrolled from different hospitals of north-eastern India. The p53 codon72 Arg>Pro polymorphism was typed by polymerase chain reaction, which showed an association with NPC risk. In the meta-analysis consisting of 1842 cases and 2330 controls, it was found that individuals carrying the Pro allele and the ProPro genotype were at a significantly higher risk for NPC as compared with those with the Arg allele and the ArgArg genotype, respectively. Individuals with a ProPro genotype and a combined Pro genotype (ProPro+ArgPro) also showed a significantly higher risk for NPC over a wild homozygote ArgArg genotype. Additionally, the strength of each study was tested by power analysis and genotype distribution by Hardy–Weinberg equilibrium. The outcome of the study indicated that both allele frequency and genotype distribution of p53 codon72 Arg>Pro polymorphism were significantly associated with NPC risk. Stratified analyses based on ethnicity and source of samples supported the above result.
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WU MUYUN, HUANG SHUJING, LIU DONG, PENG MIAO, YANG FAN, WANG XICHENG. Association of the p53 or GSTM1 polymorphism with the risk of nasopharyngeal carcinoma: A meta-analysis. Mol Clin Oncol 2016; 4:221-228. [PMID: 26893866 PMCID: PMC4734025 DOI: 10.3892/mco.2015.700] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/11/2015] [Accepted: 11/12/2015] [Indexed: 12/08/2022] Open
Abstract
p53 and glutathione S-transferase M1 (GSTM1) are the most popular suppressor genes. Several previous studies demonstrated positive associations of these gene polymorphisms with numerous cancer types, including hepatocellular cancer, while the association between p53/GSTM1 polymorphisms and the nasopharyngeal carcinoma (NPC) risk was inconsistent and underpowered. However, no studies investigating the combinational effect of these two genes on NPC risk were performed. To confirm the effects of p53 and GSTM1 polymorphisms on the risk of NPC, a meta-analysis of all the available previous studies associating p53 and GSTM1 with the risk of NPC was performed. A comprehensive search of PubMed, Web of Science and SD database until November 2014 was performed to identify the relevant studies. The data were extracted by two independent authors and pooled odds ratio (OR) with 95% confidence interval (CI) was calculated. Meta-regression and subgroup analyses were performed to identify the source of heterogeneity. Finally, five studies with 1,419 cases and 1,707 controls were included for the p53 polymorphism and three studies with 837 cases and 1,299 controls were included for the GSTM1 polymorphism. Regarding p53, a significantly increased NPC risk was observed in the overall population (C vs. G, OR, 1.245; 95% CI, 1.045-1.483; P=0.014; additive models: CC vs. GG, OR, 1.579; 95% CI, 1.100-2.265; P=0.013 and CG vs. GG, OR, 1.230; 95% CI, 1.039-1.456; P=0.016; dominant model, OR, 1.321; 95% CI, 1.127-1.549; P=0.001; recessive model, OR, 1.429; 95% CI, 1.017-2.009; P=0.040). Concerning GSTM1, a significantly increased NPC risk was observed in the overall population (null versus non-null, OR, 1.282; 95% CI, 1.075-1.530; P=0.006). In the subgroup analyses stratified by the source of controls, a significant association of p53 with NPC risk was also demonstrated, while no association with GSTM1 was observed. Therefore, the p53 G72C polymorphism may have a susceptible role in the carcinogenesis of NPC, while genetic deletion of GSTM1 may contribute to increased susceptibility to NPC. Further large and well-designed studies are required to confirm this association.
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Affiliation(s)
- MUYUN WU
- Department of Oncology, The Fifth People's Hospital of Wuhu, Wuhu, Anhui 241000, P.R. China
| | - SHUJING HUANG
- Department of Oncology, First Affiliated Hospital of Guangdong Pharmaceutical University, Guangzhou, Guangdong 510080, P.R. China
| | - DONG LIU
- Department of Internal Medicine, Guangdong Pharmaceutical University, Guangzhou, Guangdong 510006, P.R. China
| | - MIAO PENG
- Department of Oncology, First Affiliated Hospital of Guangdong Pharmaceutical University, Guangzhou, Guangdong 510080, P.R. China
| | - FAN YANG
- Department of Oncology, First Affiliated Hospital of Guangdong Pharmaceutical University, Guangzhou, Guangdong 510080, P.R. China
| | - XICHENG WANG
- Department of Oncology, First Affiliated Hospital of Guangdong Pharmaceutical University, Guangzhou, Guangdong 510080, P.R. China
- Correspondence to: Mr. Xicheng Wang, Department of Oncology, First Affiliated Hospital of Guangdong Pharmaceutical University, Guangzhou, Guangdong 510080, P.R. China, E-mail:
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Hori Y, Miyabe K, Yoshida M, Nakazawa T, Hayashi K, Naitoh I, Shimizu S, Kondo H, Nishi Y, Umemura S, Kato A, Ohara H, Inagaki H, Joh T. Impact of TP53 codon 72 and MDM2 SNP 309 polymorphisms in pancreatic ductal adenocarcinoma. PLoS One 2015; 10:e0118829. [PMID: 25734904 PMCID: PMC4348172 DOI: 10.1371/journal.pone.0118829] [Citation(s) in RCA: 17] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/24/2014] [Accepted: 12/02/2014] [Indexed: 12/16/2022] Open
Abstract
Single-nucleotide polymorphisms (SNPs) of TP53 (codon 72, rs1042522) and MDM2 promoter (SNP 309, rs2279744) have been associated with risk for various human cancers. However, studies analyzing these polymorphisms in pancreatic ductal adenocarcinoma (PDAC) are lacking. We investigated TP53 codon 72 and MDM2 SNP 309 polymorphisms in 32 patients with PDAC, 16 patients with chronic pancreatitis (CP), and 32 normal controls, using formalin-fixed paraffin-embedded tissue. We also examined TP53 and MDM2 protein immunohistochemistry (IHC) to assess the involvement of these differences in malignant transformation and disease progression. TP53 Pro/Pro genotype was significantly more frequent in PDAC patients than in controls (65.6 vs. 15.6%, p < 0.001) and no significant difference was found between CP patients (37.5%) and controls. In MDM2 SNP 309, there were no significant differences among the three groups. Based on the Kaplan-Meier analysis, overall survival was significantly shorter in MDM2 G/G genotypes compared with other genotypes (G/T and T/T) (359 vs. 911 days, p = 0.016) whereas no significant differences in TP53 genotypes were observed (638 vs. 752 days, p = 0.471). Although TP53 IHC was frequent in PDAC patients (53.1%), TP53 and MDM2 protein expression was not correlated with polymorphisms. Our study demonstrated TP53 codon 72 polymorphism is potentially a genetic predisposing factor while MDM2 SNP 309 polymorphism might be useful in predicting survival outcome.
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Affiliation(s)
- Yasuki Hori
- Department of Gastroenterology and Metabolism, Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan
| | - Katsuyuki Miyabe
- Department of Gastroenterology and Metabolism, Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan
| | - Michihiro Yoshida
- Department of Gastroenterology and Metabolism, Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan
| | - Takahiro Nakazawa
- Department of Gastroenterology and Metabolism, Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan
| | - Kazuki Hayashi
- Department of Gastroenterology and Metabolism, Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan
| | - Itaru Naitoh
- Department of Gastroenterology and Metabolism, Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan
| | - Shuya Shimizu
- Department of Gastroenterology and Metabolism, Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan
| | - Hiromu Kondo
- Department of Gastroenterology and Metabolism, Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan
| | - Yuji Nishi
- Department of Gastroenterology and Metabolism, Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan
| | - Shuichiro Umemura
- Department of Gastroenterology and Metabolism, Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan
| | - Akihisa Kato
- Department of Gastroenterology and Metabolism, Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan
| | - Hirotaka Ohara
- Department of Community-based Medical Education, Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan
| | - Hiroshi Inagaki
- Department of Pathology and Molecular Diagnostics, Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan
| | - Takashi Joh
- Department of Gastroenterology and Metabolism, Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan
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7
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The association between gene polymorphisms and risk of nasopharyngeal carcinoma. Med Oncol 2014; 32:398. [PMID: 25481674 DOI: 10.1007/s12032-014-0398-5] [Citation(s) in RCA: 10] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/19/2014] [Accepted: 11/21/2014] [Indexed: 02/05/2023]
Abstract
Gene polymorphisms have been implicated in increased susceptibility of nasopharyngeal carcinoma, but studies have reported inconclusive results. The present study investigates the relationship between each potential gene polymorphism and the risk of nasopharyngeal carcinoma through a comprehensive series of meta-analyses. Data from Pubmed, CNKI, Wanfang and Weipu databases were collected, evaluated and analyzed. Statistical analysis was performed using the Revman 4.2 and STATA 10.0 softwares. A total of 9,705 nasopharyngeal carcinoma cases and 11,041 controls in 34 case-control studies were identified for data analysis. The results suggested that the Arg399Gln polymorphism of XRCC1 gene, the 1G/2G polymorphism of MMP-1 gene, the RsaI polymorphism of CYP2E1 gene, the -1306C>T polymorphism of MMP-2 gene and the Arg72Pro polymorphism of p53 gene might be related to increased risks of nasopharyngeal carcinoma under different genetic comparison models, while the Arg194Trp and Arg280His polymorphisms of XRCC1 gene and the 309T>G polymorphism of MDM2 gene might not contribute to the risk of nasopharyngeal carcinoma. This current meta-analysis suggests that five polymorphisms might be risk factors for nasopharyngeal carcinoma under different genetic comparison models. Future studies are needed to validate our findings.
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Adduri RSR, Katamoni R, Pandilla R, Madana SN, Paripati AK, Kotapalli V, Bashyam MD. TP53 Pro72 allele is enriched in oral tongue cancer and frequently mutated in esophageal cancer in India. PLoS One 2014; 9:e114002. [PMID: 25436609 PMCID: PMC4250174 DOI: 10.1371/journal.pone.0114002] [Citation(s) in RCA: 9] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/07/2014] [Accepted: 10/31/2014] [Indexed: 12/13/2022] Open
Abstract
Purpose The tumor suppressor p53 is known to be inactivated frequently in various cancers. In addition, germline polymorphisms in TP53 are known to affect protein function and influence risk of developing different types of cancers. In this study, we analyzed the association of TP53 Pro72Arg polymorphism with squamous cell carcinoma of oral tongue (SCCOT) and esophagus (ESCC) in India. Methods We assessed the distribution of TP53 Pro72Arg polymorphism in one hundred and fifteen and eighty two SCCOT and ESCC patients, respectively, with respect to one hundred and ten healthy controls from the same population. In addition, we analyzed association of the polymorphism with several clinico-pathological and molecular parameters. Results Pro72 allele was significantly enriched in SCCOT patients compared to the healthy control group but neither allele was enriched in ESCC. Interestingly, Pro72 allele was preferentially mutated in ESCC which was confirmed by analysis of samples heterozygous for Pro72Arg. Conclusions Our study revealed the association of Pro72 allele with SCCOT suggesting the effect of this polymorphism on SCCOT risk. Preferential mutation of Pro72 allele exclusively in ESCC indicates the need for further studies to understand the tissue specific effect of p53 polymorphism.
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Affiliation(s)
- Raju S. R. Adduri
- Laboratory of Molecular Oncology, Centre for DNA Fingerprinting and Diagnostics, Nampally, Hyderabad, India
| | - Rajender Katamoni
- Laboratory of Molecular Oncology, Centre for DNA Fingerprinting and Diagnostics, Nampally, Hyderabad, India
| | - Ramaswamy Pandilla
- Laboratory of Molecular Oncology, Centre for DNA Fingerprinting and Diagnostics, Nampally, Hyderabad, India
| | - Sandeep N. Madana
- Laboratory of Molecular Oncology, Centre for DNA Fingerprinting and Diagnostics, Nampally, Hyderabad, India
| | - Arun Kumar Paripati
- Laboratory of Molecular Oncology, Centre for DNA Fingerprinting and Diagnostics, Nampally, Hyderabad, India
| | - Viswakalyan Kotapalli
- Laboratory of Molecular Oncology, Centre for DNA Fingerprinting and Diagnostics, Nampally, Hyderabad, India
| | - Murali Dharan Bashyam
- Laboratory of Molecular Oncology, Centre for DNA Fingerprinting and Diagnostics, Nampally, Hyderabad, India
- * E-mail:
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Cai K, Wang Y, Zhao X, Bao X. Association between the P53 codon 72 polymorphism and nasopharyngeal cancer risk. Tumour Biol 2013; 35:1891-7. [PMID: 24114013 DOI: 10.1007/s13277-013-1254-5] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/26/2013] [Accepted: 09/25/2013] [Indexed: 12/12/2022] Open
Abstract
The P53 codon 72 polymorphism has been identified as a critical biomarker in modifying the risk of nasopharyngeal cancer (NPC). Many studies have investigated the association between the polymorphism of P53 codon 72 and NPC risk; however, the findings across the published studies are inconsistent and inconclusive. To acquire a more precise assessment for this association, we conducted an updated meta-analysis. The PubMed, Embase, Web of Science, and Wanfang databases were searched for relevant case-control studies. Totally, seven independent publications with 1,133 cases and 1,678 controls were retrieved. The pooled odds ratio (OR) with corresponding 95% confidence interval (95% CI) was calculated. Increased risk of NPC was observed among individuals carrying the variant allele and genotypes of P53 codon 72 (OR Pro vs. Arg = 1.32, 95% CI 1.18-1.47, P OR < 0.001; OR ProPro vs. ArgArg = 1.90, 95% CI 1.51-2.39, P OR < 0.001; OR ProArg + ProPro vs. ArgArg = 1.33, 95% CI 1.13-1.57, P OR = 0.001; OR ProPro vs. ArgArg + ProArg = 1.65, 95% CI 1.35-2.01, P OR < 0.001). Stratified analyses by ethnicity and source of controls also identified this significant relationship in Asians, Caucasians, and hospital-based case-control studies. There was no publication bias risk in our study. The updated meta-analysis supports the evidence that the polymorphism of P53 codon 72 is a risk factor for the development of NPC among the populations of both Asian and Caucasian.
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Affiliation(s)
- Kemin Cai
- Department of Otorhinolaryngology Head and Neck Surgery, People's Hospital of Taizhou, Taizhou, 225300, Jiangsu, China,
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Interactions of miR-34b/c and TP-53 polymorphisms on the risk of nasopharyngeal carcinoma. Tumour Biol 2013; 34:1919-23. [DOI: 10.1007/s13277-013-0736-9] [Citation(s) in RCA: 48] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/10/2012] [Accepted: 03/04/2013] [Indexed: 12/31/2022] Open
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Bei JX, Jia WH, Zeng YX. Familial and large-scale case-control studies identify genes associated with nasopharyngeal carcinoma. Semin Cancer Biol 2012; 22:96-106. [PMID: 22313875 DOI: 10.1016/j.semcancer.2012.01.012] [Citation(s) in RCA: 45] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/08/2011] [Revised: 01/21/2012] [Accepted: 01/24/2012] [Indexed: 12/17/2022]
Abstract
Nasopharyngeal carcinoma (NPC) is an epithelial malignancy and has a remarkable geographic distribution, which is highly prevalent in southern China, Southeast Asia, and North Africa. Although most of the NPC are sporadic cases, the familial clustering of NPC has been demonstrated worldwide. Accumulating studies have proposed that the etiology of NPC is multi-stage and multi-factorial, involving genetic lesions, Epstein-Barr virus infection, and environmental exposure. Genetic variations result in differences in gene function, which in turn lead to different susceptibility to disease. Many studies have been carried out to dissect the genetic variants that contribute to NPC susceptibility. This article reviews the current progress of genetic studies to identify genes associated with NPC, focusing on the familial linkage and large-scale case-control study designs.
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Affiliation(s)
- Jin-Xin Bei
- State Key Laboratory of Oncology in South China, Sun Yat-sen University Cancer Center, Guangzhou 510060, China
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Pandith AA, Khan NP, Rashid N, Azad N, Zaroo I, Hafiz A, Siddiqi MA. Impact of codon 72 Arg > Pro single nucleotide polymorphism in TP53 gene in the risk of kangri cancer: a case control study in Kashmir. Tumour Biol 2012; 33:927-33. [PMID: 22249977 DOI: 10.1007/s13277-012-0318-2] [Citation(s) in RCA: 9] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/17/2011] [Accepted: 01/03/2012] [Indexed: 11/30/2022] Open
Abstract
Kangri cancer found only in Kashmir (north India) is a unique thermally induced squamous cell carcinoma of the skin that develops because of chronic and persistent irritation due to the use of a kangri (a brazier) by the Kashmiri people to combat the chilling cold temperature during winter. Being unique to this region, the molecular etiology of the invasive kangri cancer is not known fully. The TP53 gene, codon 72 polymorphism (Arg72Pro), has been found to be associated with cancer susceptibility but has not been investigated in kangri cancer risk. A case control study was conducted to find the genotype distribution of TP53 Arg72Pro SNP and to elucidate the possible role of this SNP as risk factor in kangri cancer development. Using the polymerase chain reaction-restriction fragment length polymorphism approach, we tested the genotype distribution of 106 kangri cancer patients in comparison with 200 cancer-free controls from the same geographical region. A significant difference was observed between the control and kangri cancer patients with odds ratio = 2.02 and 95% confidence interval = 1.2-3.3 (p = 0.01). Interestingly, the proline form was abundantly observed in advanced-grade tumors (p < 0.05). We also found a significant association of the variant allele (GC + CC) with male subjects and patients >45 years of age (p < 0.05). Thus, it is evident from our study that Arg72Pro SNP is implicated in kangri cancer and that the rare, proline-related allele is connected with higher susceptibility to kangri cancer.
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Affiliation(s)
- Arshad A Pandith
- Department of Immunology and Molecular Medicine, Sher-I-Kashmir Institute of Medical Sciences, Soura, Srinagar, Kashmir, India 190011
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Vaji S, Salehi Z, Aminian K. Association of p53 codon 72 genetic polymorphism with the risk of ulcerative colitis in northern Iran. Int J Colorectal Dis 2011; 26:235-8. [PMID: 20669023 DOI: 10.1007/s00384-010-1021-7] [Citation(s) in RCA: 9] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 07/14/2010] [Indexed: 02/04/2023]
Abstract
PURPOSE Ulcerative colitis (UC) is a chronic inflammatory condition of the large bowel of unknown etiology, characterized by the presence of bloody diarrhea and mucus associated with a negative stool culture for bacteria, ova, or parasites. The aim of this study was to investigate the association of p53 codon 72 genetic polymorphism with the risk of UC in northern Iran. METHODS We evaluated the association of the p53 codon 72 genetic polymorphism with UC in northern Iran. The genotype of 190 patients with UC (115 men, 75 women; mean age, 32 ± 8.6 years) and 220 healthy control subjects (123 men, 97 women; mean age, 33 ± 2.5 years) were compared. Genomic DNA was extracted from colonic bioptic tissues of patients and blood samples of healthy individuals. Genotypes and allele frequencies were determined in patients and controls using allele-specific PCR (AS-PCR). RESULTS There were significant differences in the distribution of the polymorphism between the control subjects and the UC patients (P < 0.0001). Significantly increased frequencies of the Pro allele and the Pro/Pro genotype were observed in patients with UC compared with controls (Pro allele: P < 0.0001; odds ratio, 7.87; 95% confidence interval, 4.03-15.35; Pro/Pro: P < 0.0001; odds ratio, 35.21; 95% confidence interval, 12.56-98.73). CONCLUSION The p53 codon 72 genetic polymorphism is associated with UC in northern Iran.
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Affiliation(s)
- Salaheddin Vaji
- Department of Biology, Faculty of Sciences, University of Guilan, Rasht, Iran
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Saini R, Tang TH, Zain RB, Cheong SC, Musa KI, Saini D, Ismail AR, Abraham MT, Mustafa WMW, Santhanam J. Significant association of high-risk human papillomavirus (HPV) but not of p53 polymorphisms with oral squamous cell carcinomas in Malaysia. J Cancer Res Clin Oncol 2011; 137:311-20. [PMID: 20419384 DOI: 10.1007/s00432-010-0886-8] [Citation(s) in RCA: 29] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/12/2010] [Accepted: 04/06/2010] [Indexed: 02/05/2023]
Abstract
PURPOSE The purpose of this study was to evaluate the role of HPV and p53 polymorphisms in oral squamous cell carcinomas (OSCC) affecting Malaysian population. METHODS We analysed frozen samples from 105 OSCC as well as 105 oral specimens derived from healthy individuals. PCR assays targeting two regions of the virus were used. PCR amplification for the analysis of p53 codon 72 arginine/proline alleles was carried out in a separate reaction. RESULTS HPV DNA was detected in 51.4% OSCC samples, while 24.8% controls were found to be HPV positive. HPV was found to be significantly associated with OSCC (P < 0.001, OR = 4.3 after adjustment for habits) when compared to controls. High-risk HPV was found to be significantly associated with OSCC cases (P < 0.05). Demographic profiles of age, gender, race and habits were not associated with HPV presence in cases and controls. However, significantly less HPV positivity was seen in poorly differentiated compared to well-differentiated OSCCs. No significant association was found between HPV positivity and p53 polymorphisms in cases and control groups. Additionally, we found no association of codon 72 polymorphism with oral cancer. CONCLUSIONS This study indicates that high-risk HPV infection is one of the contributing factors for OSCCs. HPV 16 was the predominant type found in Malaysian patients with OSCC. Further, we did not find any association between p53 codon 72 polymorphism and HPV infection or between the p53 polymorphism and the risk of oral cancer.
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Affiliation(s)
- Rajan Saini
- School of Dental Sciences, Universiti Sains Malaysia, 16150 Kubang Kerian, Kelantan, Malaysia.
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[North African and Southeast Asian nasopharyngeal carcinomas: between the resemblance and the dissemblance]. Bull Cancer 2010; 97:475-82. [PMID: 20385521 DOI: 10.1684/bdc.2010.1090] [Citation(s) in RCA: 13] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/15/2022]
Abstract
Nasopharyngeal carcinoma (NPC) is an unusual head and neck cancer because of its unequal geographical distribution and its consistent association with the Epstein-Barr virus (EBV). This malignant tumor poses a serious public health problem in many countries, especially in Southeast Asia and North Africa where the recorded incidence are highest. During the past decade, a growing number of studies were undertaken to define the molecular basis of NPC. However, the analysis of several clinical and biological parameters of North African and Southeast Asian NPCs has shown notable differences, suggesting that they could result from a distinct combination of etiological factors. One intriguing characteristic of North African NPC, concerns its bimodal age distribution with a secondary peak of incidence in the range of 15-25 years, not observed in Asian NPC. In this juvenile form of NPC, immuno-histochemistry assay has shown that the two key proteins controlling the apoptotic-survival balance p53 and Bcl-2 are less frequently expressed whereas the transmembrane tyrosine-kinase receptor c-kit and the main EBV oncoprotein LMP1 were more abundant. In addition, the EBV serological alterations are less informative for the diagnosis of the juvenile compared to the adult form. In addition, most North African NPCs contain EBV strains with genetic polymorphisms distinct from those described in the Southeast Asia series (predominance of F, D, H1-H2, XhoI+ and f, C, H, XhoI- respectively). In contrast, studies relating on tumor chromosomal alterations or aberrant promoter methylation result in data very similar to those obtained from the Southeast Asia series, supporting the concept of a common molecular basis for all NPC regardless of patient geographic origin.
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Eduardo B, Raquel C, Rui M. Nasopharyngeal carcinoma in a south European population: epidemiological data and clinical aspects in Portugal. Eur Arch Otorhinolaryngol 2010; 267:1607-12. [PMID: 20454799 DOI: 10.1007/s00405-010-1258-3] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/02/2009] [Accepted: 04/15/2010] [Indexed: 11/26/2022]
Abstract
The incidence of nasopharyngeal carcinoma (NPC) varies worldwide, with higher rates in southern Asia, intermediate rates in Mediterranean basin countries as well as in Greenland and Alaska populations, and low rates in most of the western countries. The percentage of NPC types seems to vary according to the WHO classification. Portugal is also a Mediterranean basin country. The NPC patterns in Portuguese population is comparatively analyzed with a review of the related literature, concerning the overall incidence, male/female ratio, age of incidence, WHO type frequency, Epstein-Barr virus relationship and genetic susceptibility. The particular findings in the Portuguese population can be discussed in the light of genetic background and close relationships with potential exogenous oncogenic factors.
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Affiliation(s)
- Breda Eduardo
- Otorhinolaryngology Department, Portuguese Institute of Oncology, R. Dr. Ant. Bernardino Almeida, Porto, 4200-072, Portugal.
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Zhuo XL, Cai L, Xiang ZL, Zhuo WL, Wang Y, Zhang XY. TP53 codon 72 polymorphism contributes to nasopharyngeal cancer susceptibility: a meta-analysis. Arch Med Res 2009; 40:299-305. [PMID: 19608020 DOI: 10.1016/j.arcmed.2009.03.006] [Citation(s) in RCA: 20] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/17/2008] [Accepted: 03/02/2009] [Indexed: 11/16/2022]
Abstract
BACKGROUND AND AIMS Previously, TP53 codon 72 polymorphisms have been implicated as risk factors for various cancers. Several studies have been conducted on the association of TP53 codon 72 polymorphisms with susceptibility to nasopharyngeal carcinoma (NPC) and have yielded inconclusive results. The aim of the present study was to assess possible associations of NPC risk with TP53 codon 72 polymorphisms. METHODS We conducted a search in Medline, EMBASE, OVID, ScienceDirect, and Chinese National Knowledge Infrastructure (CNKI) without a language limitation, covering all papers published until November 2008. The associated literature was acquired through deliberate searching and selected based on the established inclusion criteria for publications. RESULTS Consequently, five studies including 394 cases and 606 controls met the included criteria and thus were selected. Ultimately, relevant data were extracted and further analyzed using systematic meta-analyses. The results showed that individuals carrying wild homozygote Arg/Arg genotype have a decreased risk of NPC compared with those carrying Pro/Pro genotype (OR: 0.46, 95% CI: 0.30-0.70). For Pro allele, no evidence indicated that individuals with a combined Pro genotype (Arg/Pro+Pro/Pro) have a significant risk of NPC compared with those with Arg/Arg genotype (OR: 0.81, 95% CI: 0.62-1.07). For Arg allele, individuals with a combined Arg genotype (Arg/Pro+Arg/Arg) have a marked decreased susceptibility to NPC relative to those with homozygote Pro/Pro genotype. CONCLUSIONS Results of the present study suggest that TP53 codon 72 polymorphisms may be a risk factor for NPC. Homozygote Pro/Pro genotype could significantly increase susceptibility to NPC, whereas Arg allele markedly decreases NPC risk.
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Affiliation(s)
- Xian-Lu Zhuo
- Department of Otolaryngology, Southwest Hospital, Third Military Medical University, Chongqing, China
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Gallì P, Cadoni G, Volante M, De Feo E, Amore R, Giorgio A, Arzani D, Paludetti G, Ricciardi G, Boccia S. A case-control study on the combined effects of p53 and p73 polymorphisms on head and neck cancer risk in an Italian population. BMC Cancer 2009; 9:137. [PMID: 19426493 PMCID: PMC2686724 DOI: 10.1186/1471-2407-9-137] [Citation(s) in RCA: 36] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/23/2008] [Accepted: 05/08/2009] [Indexed: 02/08/2023] Open
Abstract
Background The purpose of this study is to analyze the combined effects of selected p53 and p73 polymorphisms and their interaction with lifestyle habits on squamous cell carcinoma of the head and neck (SCCHN) risk and progression in an Italian population. Methods Two hundred and eighty-three cases and 295 hospital controls were genotyped for p53 polymorphisms on exon 4 (Arg72Pro), intron 3 and 6, and p73 G4C14-to-A4T14. Their association with SCCHN was estimated using a logistic regression analysis, while a multinomial logistic regression approach was applied to calculate the effect of the selected polymorphisms on SCCHN different sites (oral cavity, oropharynx, hypopharynx and larynx). We performed an haplotype analysis of the p53 polymorphisms, and a gene-gene interaction analysis for the combined effects of p73 G4C14-to-A4T14 and p53 polymorphisms. Results We found a significant increased risk of SCCHN among individuals with combined p73 exon 2 G4A and p53 intron 3 variant alleles (OR = 2.22, 95% CI: 1.08–4.56), and a protective effect for those carrying the p53 exon 4-p53 intron 6 diplotype combination (OR = 0.67; 95% CI: 0.47–0.92). From the gene-environment interaction analysis we found that individuals aged < 45 years carrying p73 exon 2 G4A variant allele have a 12.85-increased risk of SCCHN (95% CI: 2.10–78.74) compared with persons of the same age with the homozygous wild type genotype. Improved survival rate was observed among p53 intron 6 variant allele carriers (Hazard Ratio = 0.51 (95% CI: 0.23–1.16). Conclusion Our study provides for the first time evidence that individuals carrying p53 exon 4 and p53 intron 6 variant alleles are significantly protected against SCCHN, and also shows that an additional risk is conferred by the combination of p73 exon 2 G4C14-to-A4T14 and p53 intron 3 variant allele. Larger studies are required to confirm these findings.
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Affiliation(s)
- Paola Gallì
- Institute of Hygiene Università Cattolica del Sacro Cuore, Rome, Italy.
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Contribution of polymorphism in codon 72 of TP53 gene to laryngeal cancer in Polish patients. Oral Oncol 2008; 45:683-6. [PMID: 19091625 DOI: 10.1016/j.oraloncology.2008.10.009] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/04/2008] [Revised: 10/20/2008] [Accepted: 10/21/2008] [Indexed: 12/28/2022]
Abstract
The amino acid substitution Arg72Pro in the TP53 protein has an impact on the biochemical and biological activity of this protein, and is associated with several types of cancers. However, the Arg72Pro polymorphism exhibits inconsistent contribution as a risk factor in various cancer types. Therefore, using PCR-RFLPs, we investigated the distribution of Arg72Pro genotypes and alleles in patients with laryngeal cancer (n=123) and controls (n=300) in Poland. We observed that patients with the Pro/Pro and Arg/Pro TP53 genotypes displayed a 1.755-fold increased risk of laryngeal cancer (95% CI=1.149-2.680, P=0.0099). However, we did not find a significant increase in laryngeal cancer risk for the homozygous Pro/Pro TP53 genotype OR=2.093 (95% CI=1.046-4.192, P=0.0530). This result suggests that the TP53Pro variant may contribute to the risk of laryngeal cancer development in Polish patients.
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Zhu ZZ, Wang AZ, Jia HR, Jin XX, He XL, Hou LF, Zhu G. Association of the TP53 codon 72 polymorphism with colorectal cancer in a Chinese population. Jpn J Clin Oncol 2008; 37:385-90. [PMID: 17599946 DOI: 10.1093/jjco/hym034] [Citation(s) in RCA: 45] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/21/2022] Open
Abstract
A TP53 gene polymorphism, resulting in an arginine (R) to proline (P) at codon 72 (TP53 R72P), has been associated with the susceptibility to various cancers. To better understand the role of this polymorphism in colorectal cancer etiology, we examined the association between TP53 R72P and colorectal cancer risk in 345 patients with colorectal cancer and 670 controls in a Chinese population. We observed that subjects with RP and PP genotypes had a 1.60-fold and a 2.37-fold increased risk for colorectal cancer, respectively. The 72P allele conferred a more pronounced increase in colorectal cancer risk among alcohol consumers (heterozygotes: OR = 3.01; homozygotes: OR = 4.71). The TP53 R72P polymorphism was not linked to tumor location, histologic grade, lymph node metastases, Dukes stage, p53 positivity, or age at diagnosis, but to tumor size. We conclude that the TP53 R72P polymorphism may contribute to the etiology of colorectal cancer in the Chinese population, particularly among alcohol consumers.
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Affiliation(s)
- Zhong-Zheng Zhu
- Department of Pathology, No. 113 Hospital of People's Liberation Army, Ningbo, Zhejiang Province, China.
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Bittenbring J, Parisot F, Wabo A, Mueller M, Kerschenmeyer L, Kreuz M, Truemper L, Landt O, Menzel A, Pfreundschuh M, Roemer K. MDM2 gene SNP309 T/G and p53 gene SNP72 G/C do not influence diffuse large B-cell non-Hodgkin lymphoma onset or survival in central European Caucasians. BMC Cancer 2008; 8:116. [PMID: 18433491 PMCID: PMC2375899 DOI: 10.1186/1471-2407-8-116] [Citation(s) in RCA: 20] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/30/2007] [Accepted: 04/23/2008] [Indexed: 11/17/2022] Open
Abstract
Background SNP309 T/G (rs2279744) causes higher levels of MDM2, the most important negative regulator of the p53 tumor suppressor. SNP72 G/C (rs1042522) gives rise to a p53 protein with a greatly reduced capacity to induce apoptosis. Both polymorphisms have been implicated in cancer. The SNP309 G-allele has recently been reported to accelerate diffuse large B-cell lymphoma (DLBCL) formation in pre-menopausal women and suggested to constitute a genetic basis for estrogen affecting human tumorigenesis. Here we asked whether SNP309 and SNP72 are associated with DLBCL in women and are correlated with age of onset, diagnosis, or patient's survival. Methods SNP309 and SNP72 were PCR-genotyped in a case-control study that included 512 controls and 311 patients diagnosed with aggressive NHL. Of these, 205 were diagnosed with DLBCL. Results The age of onset was similar in men and women. The control and patients group showed similar SNP309 and SNP72 genotype frequencies. Importantly and in contrast to the previous findings, similar genotype frequencies were observed in female patients diagnosed by 51 years of age and those diagnosed later. Specifically, 3/20 female DLBCL patients diagnosed by 51 years of age were homozygous for SNP309 G and 2/20 DLBCL females in that age group were homozygous for SNP72 C. Neither SNP309 nor SNP72 had a significant influence on event-free and overall survival in multivariate analyses. Conclusion In contrast to the previous study on Ashkenazi Jewish Caucasians, DLBCL in pre-menopausal women of central European Caucasian ethnicity was not associated with SNP309 G. Neither SNP309 nor SNP72 seem to be correlated with age of onset, diagnosis, or survival of patients.
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Affiliation(s)
- Joerg Bittenbring
- Internal Medicine I and Josè Carreras Research Center, University of Saarland Medical School, Homburg-Saar, Germany.
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Yoon YJ, Chang HY, Ahn SH, Kim JK, Park YK, Kang DR, Park JY, Myoung SM, Kim DY, Chon CY, Han KH. MDM2 and p53 polymorphisms are associated with the development of hepatocellular carcinoma in patients with chronic hepatitis B virus infection. Carcinogenesis 2008; 29:1192-6. [DOI: 10.1093/carcin/bgn090] [Citation(s) in RCA: 103] [Impact Index Per Article: 6.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/24/2022] Open
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Proline homozygosity in codon 72 of TP53 is a factor of susceptibility to nasopharyngeal carcinoma in Tunisia. ACTA ACUST UNITED AC 2007; 178:89-93. [DOI: 10.1016/j.cancergencyto.2007.05.013] [Citation(s) in RCA: 19] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/11/2006] [Revised: 05/15/2007] [Accepted: 05/17/2007] [Indexed: 11/20/2022]
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Perrone F, Mariani L, Pastore E, Orsenigo M, Suardi S, Marcomini B, DaRiva L, Licitra L, Carbone A, Pierotti MA, Pilotti S. p53 codon 72 polymorphisms in human papillomavirus-negative and human papillomavirus-positive squamous cell carcinomas of the oropharynx. Cancer 2007; 109:2461-5. [PMID: 17492690 DOI: 10.1002/cncr.22702] [Citation(s) in RCA: 19] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/05/2023]
Abstract
BACKGROUND Tobacco smoking, alcohol abuse, and high-risk human papillomavirus (HPV) are risk factors in the etiology of oropharyngeal squamous cell carcinomas (SCCs). The TP53 polymorphism, in which an arginine (R) is changed to proline (P) at codon 72, is functionally significant and could therefore be a predisposing genetic defect. METHODS The aim of the study was to investigate the role of codon 72 polymorphism by means of double gradient-denaturing gel electrophoresis in 77 oropharyngeal SCC patients including 33 TP53 mutated and 16 HPV-16-positive cases. The controls consisted of 141 consecutive healthy blood donors. RESULTS The cases and controls showed significantly different genotype distribution (P = .0005): the frequencies of the RR, RP, and PP genotypes among the cases were, respectively, 81.8%, 10.4%, and 7.8%, as opposed to 59.6%, 33.3%, and 7.1% among the controls, in agreement with the Hardy-Weinberg equilibrium (P = .35). The PP genotype was significantly overrepresented among females (22.2% vs 3.4%; P = .0243) and in HPV-16-positive cases (25.0% vs 3.3%; P = .0152). No segregation was found between either of the codon 72 genotypes and age or TP53 mutations. CONCLUSIONS The significantly lower frequency of the RP genotype in the patients as a whole suggests that it has a protective effect on oropharyngeal SCCs. Moreover, the PP genotype may be a risk factor for the development of oropharyngeal SCC by females and the development of HPV-16-related SCC, although the findings need to be validated in a larger number of tumors.
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Affiliation(s)
- Federica Perrone
- Unit of Experimental Molecular Pathology, Fondazione IRCCS Istituto Nazionale per lo Studio e la Cura dei Tumori, Milan, Italy.
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Kuroda Y, Nakao H, Ikemura K, Katoh T. Association between the TP53 codon72 polymorphism and oral cancer risk and prognosis. Oral Oncol 2007; 43:1043-8. [PMID: 17306604 DOI: 10.1016/j.oraloncology.2006.12.001] [Citation(s) in RCA: 18] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/03/2006] [Revised: 12/01/2006] [Accepted: 12/01/2006] [Indexed: 11/25/2022]
Abstract
The TP53 codon72 polymorphism has recently been extensively studied to determine the risk factor for carcinogenesis. However, there are few reports about the relationship between the TP53 codon72 polymorphism and oral cancer risk or post treatment prognosis. We evaluated the genotypic distribution of the TP53 codon72 polymorphism in 100 oral cancer cases and 271 non-cancer controls. There were no significant differences in the frequencies of the three genotypes (Arg/Arg, Arg/Pro, Pro/Pro) of the TP53 codon72 polymorphism between oral cancer cases and controls. However, stratifying by smoking status, we found that the adjusted odds ratio for non-smokers with the Pro/Pro genotype was significantly increased (adjusted OR=2.70, 95% confidence interval=1.07-6.82). We also found that the cases with the Pro/Pro genotype tended to have a shorter post-treatment survival compared with those with the Arg/Pro genotype (p=0.06). Our results suggest the Pro/Pro genotype of the TP53 codon72 polymorphism increases oral cancer risk in non-smokers and worsens their prognosis.
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Affiliation(s)
- Yoshiki Kuroda
- Department of Public Health, Faculty of Medicine, University of Miyazaki, 5200, Kihara, Kiyotake, Miyazaki 889-1692, Japan.
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Sousa H, Santos AM, Catarino R, Pinto D, Vasconcelos A, Lopes C, Breda E, Medeiros R. Linkage of TP53 codon 72 pro/pro genotype as predictive factor for nasopharyngeal carcinoma development. Eur J Cancer Prev 2007; 15:362-6. [PMID: 16835507 DOI: 10.1097/00008469-200608000-00010] [Citation(s) in RCA: 26] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
Genetic predisposition has been suggested as a cofactor for cancer aetiology and a polymorphism in TP53 codon 72 has been associated as a susceptibility factor for several cancers. Nasopharyngeal carcinoma is a rare neoplasia in western civilizations and genetic predisposition might play an important role in its development. We evaluated the linkage of the polymorphic variants (Arg/Pro) on TP53 codon 72 with nasopharyngeal cancer development in a case-control study with 392 individuals from a northern Portuguese population, including 107 patients with nasopharyngeal carcinoma and 285 healthy controls. This study revealed a three-fold risk for carriers of Pro/Pro genotype either against carriers of Arg/Arg (OR=2.62; 95% CI=1.10-6.30; P=0.016) or total Arg carriers (OR=2.67; 95% CI=1.21-5.90; P=0.012). Moreover, step-wise logistic regression analysis identified Pro/Pro genotype (OR=3.1; 95% CI=1.3-7.3; P=0.009), age >49 at diagnosis (OR=2.5; 95% CI=1.6-4.0; P<0.001) and male gender (OR=2.7; 95% CI=1.6-4.4; P<0.001) as predictive factors for the development of nasopharyngeal carcinoma. These results confirm the data from Asiatic populations suggesting that Pro/Pro genotype represents a stable risk factor for nasopharyngeal carcinoma development in Portugal and that TP53 codon 72 polymorphism can contribute as a genetic susceptibility marker, providing additional information to improve the knowledge about nasopharyngeal carcinoma aetiology.
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Affiliation(s)
- Hugo Sousa
- Molecular Oncology Unit, Portuguese Institute of Oncology - Oporto, Porto, Portugal
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Morari EC, Lima ABC, Bufalo NE, Leite JL, Granja F, Ward LS. Role of glutathione-S-transferase and codon 72 of P53 genotypes in epithelial ovarian cancer patients. J Cancer Res Clin Oncol 2006; 132:521-8. [PMID: 16788846 DOI: 10.1007/s00432-006-0099-3] [Citation(s) in RCA: 31] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/12/2005] [Accepted: 04/12/2006] [Indexed: 10/24/2022]
Abstract
PURPOSE A series of polymorphisms in germ-line DNA have been investigated in an effort to delineate polygenic models of cancer susceptibility and prognosis. As low-penetrance susceptibility genes may combine additively or multiplicatively and contribute to cancer incidence and to the response to chemotherapy, we studied GSTT1, GSTM1, GSTO2, GSTP1 and codon 72 of p53 genotype profiles in ovarian cancer patients. METHODS We compared 69 ovarian cancer patients with 222 control healthy women paired for ethnic and life-style characteristics. Outcome was evaluated in 29 stage III and IV patients submitted to a platinum-based chemotherapy followed-up for 6-29 months (17 +/- 9 months). RESULTS GSTT1, GSTM1, GSTO2 and GSTP1 genes presented a similar genotype distribution, but codon 72 of p53 gene wild-type variant was less frequent in ovarian cancer patients than in controls (chi(2); P = 0.0004). CONCLUSIONS We were unable to demonstrate any association between the GST genotypes studied and the risk of ovarian cancer but the inheritance of a heterozygous Arg/Pro genotype of p53 increased the risk of ovarian cancer more than 2.5 times (OR = 2.571; 95% CI = 1.453-4.550). There was no association of the studied genes to any clinical or pathological feature of the patients or to their response to chemotherapy.
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Affiliation(s)
- Elaine Cristina Morari
- Laboratory of Cancer Molecular Genetics, Department of Medicine, Medical Sciences Faculty, State University of Campinas-UNICAMP, Tessalia Vieira de Camargo 126, 13084-970, Campinas, São Paulo, Brazil
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Abstract
The p53 tumor suppressor gene continues to be distinguished as the most frequently mutated gene in human cancer; this gene can be found mutated in up to 50% of human tumors of diverse histological type. It is generally accepted that the ability of p53 to induce either growth arrest or programmed cell death in response to diverse stimuli underlies the powerful selection against this protein in the development of cancer. It is somewhat surprising, then, to find p53 and several target genes in this pathway containing polymorphisms that impair their function. The nature of these polymorphic variants, and the mechanism whereby they impair the function of the p53 pathway, are reviewed here-in. The impact of these polymorphisms on cancer risk and the efficacy of therapy are only now becoming unraveled. Of particular relevance in these efforts will be the generation of mouse models of polymorphic variants in p53 and its target genes. Equally important will be better-controlled human studies, where-in haplotypes for p53 (that is, combinations of different polymorphisms in the p53 gene) and for p53-target genes are taken into account, instead of analyses of single gene variants, which have largely predominated to date. Studies in both regards should shed light on an emerging area in cancer biology, the significance of inter-individual differences in genotype on cancer risk, prognosis, and the efficacy of cancer therapy.
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Affiliation(s)
- E C Pietsch
- Division of Medical Sciences, Fox Chase Cancer Center, Philadelphia, PA 19111, USA
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Twu CW, Jiang RS, Shu CH, Lin JC. Association of p53 Codon 72 Polymorphism with Risk of Hypopharyngeal Squamous Cell Carcinoma in Taiwan. J Formos Med Assoc 2006; 105:99-104. [PMID: 16477330 DOI: 10.1016/s0929-6646(09)60330-2] [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: 12/20/2022] Open
Abstract
BACKGROUND p53 polymorphism at codon 72 is a known risk marker for various malignancies, but it has not been studied in hypopharyngeal cancer. This study investigated the genotype distribution of p53 codon 72 polymorphism in hypopharyngeal cancer patients and non-cancer controls matched for age, gender, alcohol consumption and smoking habit. METHODS Genomic DNA was extracted from peripheral blood cells of 53 patients with hypopharyngeal cancer and 53 non-cancer controls. Codon 72 polymorphism of p53 was identified by polymerase chain reaction-restriction fragment length polymorphism. RESULTS Patients with hypopharyngeal cancer had higher frequencies of Pro/Pro (26.4% vs. 13.2%) and Pro/Arg (51.0% vs. 45.3%) but lower frequencies of Arg/Arg (22.6% vs. 45.1%) compared to controls. Compared to Arg/Arg genotypes, Pro/Pro genotypes had a relative risk of hypopharyngeal cancer of 3.667 (95% confidence interval, 1.16-11.56; p = 0.03). As a group, patients with Pro/Pro or Arg/Pro who were carriers of the Pro allele had a higher relative risk of hypopharyngeal cancer compared to Arg homozygous carriers (odds ratio, 2.415; 95% confidence interval, 1.04-5.64; p = 0.04). CONCLUSION This study demonstrated that p53 codon 72 Pro homozygosity is associated with a higher risk of developing hypopharyngeal cancer.
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Affiliation(s)
- Chih-Wen Twu
- Institute of Clinical Medicine, National Yang-Ming University, Taipei, Taiwan, ROC
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30
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Zhu ZZ, Cong WM, Liu SF, Xian ZH, Wu WQ, Wu MC, Gao B, Hou LF, Zhu GS. A p53 polymorphism modifies the risk of hepatocellular carcinoma among non-carriers but not carriers of chronic hepatitis B virus infection. Cancer Lett 2005; 229:77-83. [PMID: 15979781 DOI: 10.1016/j.canlet.2005.04.014] [Citation(s) in RCA: 28] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/31/2005] [Revised: 04/08/2005] [Accepted: 04/11/2005] [Indexed: 12/28/2022]
Abstract
To clarify the modifying effect of the codon 72 p53 polymorphism on hepatocellular carcinoma (HCC) stratified by chronic hepatitis B virus (HBV) infection status, 111 incident cases of HCC and 424 controls in HBV-negative subjects and 135 cases and 125 controls in HBV-positive subjects were identified. No correlation between the polymorphism and HCC risk was found when comparing the HBV-positive cases to controls. However, in HBV-negative subjects, Arg/Pro and Pro/Pro genotypes had a 1.97-fold and a 3.36-fold increased risk for HCC, respectively. In subjects with the Pro allele and family history of HCC yielded an 11.81-fold increased risk of HCC.
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Affiliation(s)
- Zhong-Zheng Zhu
- Department of Pathology, Eastern Hepatobiliary Surgery Hospital, No. 225 Changhai Road, 200438 Shanghai, People's Republic of China
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31
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Jones JS, Chi X, Gu X, Lynch PM, Amos CI, Frazier ML. p53 polymorphism and age of onset of hereditary nonpolyposis colorectal cancer in a Caucasian population. Clin Cancer Res 2005; 10:5845-9. [PMID: 15355915 DOI: 10.1158/1078-0432.ccr-03-0590] [Citation(s) in RCA: 58] [Impact Index Per Article: 2.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/16/2022]
Abstract
PURPOSE Hereditary nonpolyposis colorectal cancer (HNPCC) is an autosomal dominant syndrome of familial malignancies. Colorectal and endometrial cancers are most frequently observed. The syndrome results mainly from germ-line mutations in DNA mismatch repair genes. A common G-to-C polymorphism at codon 72 in the p53 gene has been associated with increased risk for lung, nasopharyngeal, oral, prostate, and breast cancers and may be a marker for genetic susceptibility to colorectal cancer. We studied the influence of this p53 polymorphism on HNPCC age of onset. EXPERIMENTAL DESIGN We determined the p53 genotype of 92 Caucasian mismatch repair mutation carriers, of which, 47 had colorectal cancer. The subjects were genotyped by single-strand conformational polymorphism analysis. We tested the association between age of onset and the p53 genotypes by comparing Kaplan-Meier survival curves, evaluating the homogeneity of the curves using the log-rank test and Wilcoxon's test, and estimating the association using the Cox proportional hazards regression model to adjust for potential demographic confounding factors. RESULTS The HNPCC patients who were heterozygous developed their colorectal cancer 13 years earlier than HNPCC patients who were homozygous for the wild-type allele. CONCLUSIONS Combining knowledge of an individual's p53 genotype with information on other genetic and environmental risk factors may improve risk estimates and help to identify individuals who are genetically susceptible to developing HNPCC at an earlier age.
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Affiliation(s)
- J Shawn Jones
- Department of Epidemiology, University of Texas M. D. Anderson Cancer Center, Houston, Texas, USA
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Zhu ZZ, Cong WM, Liu SF, Dong H, Zhu GS, Wu MC. Homozygosity for Pro of p53 Arg72Pro as a potential risk factor for hepatocellular carcinoma in Chinese population. World J Gastroenterol 2005; 11:289-92. [PMID: 15633234 PMCID: PMC4205420 DOI: 10.3748/wjg.v11.i2.289] [Citation(s) in RCA: 31] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
Abstract
AIM: Codon 72 exon 4 polymorphism (Arg72Pro) of the p53 gene has been implicated in cancer risk. Our objective was to investigate the possible association between p53 Arg72Pro polymorphism and susceptibility to hepatocellular carcinoma (HCC) among Chinese population.
METHODS: The p53 Arg72Pro genotypes were determined by PCR-based restriction fragment length polymorphism (RFLP) analysis in 507 HCC cases and 541 controls. Odds ratios (ORs) for HCC and 95% confidence intervals (CIs) from unconditional logistic regression models were used to evaluate relative risks. Potential risk factors were included in the logistic regression models as covariates in the multivariate analyses on genotype and HCC.
RESULTS: The frequencies for Pro and Arg alleles were 44.5%, 55.5% in HCC cases, and 40.3% and 59.7% in controls, respectively. The Pro allele was significantly associated with the presence of HCC (P = 0.05) and had a higher risk for HCC (OR = 1.19, 95% CI 1.00-1.41) as compared with the Arg allele. After adjusted for potential risk factors, Arg/Pro heterozygotes had an 1.21-fold increased risk (95% CI 0.82-1.78, P = 0.34) of HCC compared with Arg homozygotes, whereas the risk for Pro homozygotes was 1.79 (95% CI 1.06-3.01, P = 0.03) times higher than that for Arg homozygotes. Pro-allele carriers had a higher relative risk of HCC than the Arg-only carriers (adjusted OR = 1.33, 95% CI 0.92-1.92, P = 0.13), although the difference was not statistically significant.
CONCLUSION: Homozygosity for Pro of p53 Arg72Pro is potentially one of the genetic risk factors for HCC in Chinese population. The p53 Arg72Pro polymorphism may be used as a stratification marker in screening individuals at a high risk of HCC.
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Affiliation(s)
- Zhong-Zheng Zhu
- Department of Pathology, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, Shanghai 200438, China
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Granja F, Morari J, Morari EC, Correa LAC, Assumpção LVM, Ward LS. Proline homozygosity in codon 72 of p53 is a factor of susceptibility for thyroid cancer. Cancer Lett 2004; 210:151-7. [PMID: 15183530 DOI: 10.1016/j.canlet.2004.01.016] [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: 09/06/2003] [Revised: 01/25/2004] [Accepted: 01/27/2004] [Indexed: 11/20/2022]
Abstract
A common germline polymorphism of p53 gene produces an Arginine to Proline change at aminoacid position 72. The resulting codon 72 variants have been reported associated with tumor susceptibility since they reduce p53 ability to activate apoptosis. Codon 72 polymorphism may play a role in subside vulnerability to different carcinogens and might account for ethnic variations in cancer frequency. Using an allele-specific polymerase chain reaction (PCR), we tested peripheral blood samples from 98 patients with thyroid cancer, including 21 follicular (FC) and 77 papillary carcinomas (PC), 44 patients with benign nodules, including 14 follicular adenomas and 30 goiters and 153 healthy individuals from the same geographical region. Data on lifetime occupational history, smoking history, general health conditions, previous diseases and other anamnestic data were obtained through interviews. Patients with FC (Pro/Pro = 19.0%, Arg/Arg = 42.9%, Arg/Pro = 38%) and with PC (Pro/Pro = 10.3%, Arg/Arg = 36.36%, Arg/Pro = 53.24%) showed a significant overrepresentation of codon 72 variants compared to the control population (Pro/Pro = 1.9%, Arg/Arg = 33.3%, Arg/Pro = 64.7%) (P = 0.0015). The Pro/Pro genotype, after adjusting for gender, age, tobacco and drugs, was associated with a markedly higher risk of FC (OR=9.714; CI: 2.334-40.436) and of PC (OR=5.299; CI: 2.334-40.436). These results provide evidence that p53 polymorphism is implicated in thyroid carcinogenesis and that individuals harboring the Pro/Pro genotype have an increased risk of developing thyroid cancer.
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Affiliation(s)
- Fabiana Granja
- Laboratory of Cancer Molecular Genetics, Department of Medicine, State University of Campinas, Olympio Pattaro 45, Campinas, São Paulo, Brazil
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Cortezzi SS, Provazzi PJ, Sobrinho JS, Mann-Prado JC, Reis PMP, de Freitas SEN, Filho JFG, Fukuyama EE, Cordeiro JA, Cury PM, Maniglia JV, Villa LL, Tajara EH, Rahal P. Analysis of human papillomavirus prevalence and TP53 polymorphism in head and neck squamous cell carcinomas. ACTA ACUST UNITED AC 2004; 150:44-9. [PMID: 15041222 DOI: 10.1016/j.cancergencyto.2003.07.010] [Citation(s) in RCA: 19] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/18/2003] [Revised: 07/04/2003] [Accepted: 07/29/2003] [Indexed: 12/29/2022]
Abstract
Head and neck squamous cell carcinoma is a disease associated with tobacco and alcohol abuse. There is evidence that the oncogenic human papillomavirus (HPV) may also be a risk for upper aerodigestive tract cancers. High-risk HPVs encode two early proteins, E6 and E7, that can bind to p53 and pRb, respectively, and induce its degradation or inactivation. The TP53 gene has a single polymorphism at codon 72 of exon 4 that encodes either arginine (Arg) or proline (Pro). The purpose of this study was to evaluate the role of HPV infection and TP53 polymorphism in head and neck cancer. We analyzed 50 tumors, as well swabs of oral mucosa from 142 control individuals, with a polymerase chain reaction technique. The prevalence of HPV in controls was 10.6% and in cancer specimens 16%. The frequency distribution of genotypes in controls was 50% Arg/Arg, 43% Arg/Pro and 7% Pro/Pro; in tumors, it was 52% Arg/Arg, 32% Arg/Pro, and 16% Pro/Pro. Contrary to the results of some studies on cervical cancer, no association between any TP53 genotype or allele and the development of head and neck cancer was observed, regardless of HPV status, except for the Pro/Pro genotype, which is associated with the absence of HPV. The arginine allele appears to protect against head and neck cancers. Also, the data showed that HPV infection results in no increased risk of developing head and neck tumors.
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Affiliation(s)
- Sylvia Sanches Cortezzi
- Instituto de Biociências, Letras e Ciências Exatas, IBILCE/UNESP, Rua Cristóvão Colombo, 2265, CEP 15054-000, São José do Rio Preto, SP, Brazil
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Tiwawech D, Srivatanakul P, Karaluk A, Ishida T. The p53 codon 72 polymorphism in Thai nasopharyngeal carcinoma. Cancer Lett 2003; 198:69-75. [PMID: 12893432 DOI: 10.1016/s0304-3835(03)00283-0] [Citation(s) in RCA: 32] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/09/2022]
Abstract
Nasopharyngeal carcinoma (NPC) is a serious cancer in Thailand. To address on the genetic risk factor for NPC, we investigated association between the p53 codon 72 polymorphism (Pro/Arg) and NPC susceptibility in the Thai. The genotype frequency of this polymorphism in 102 NPC patients and 148 age-matched healthy controls was determined by using a PCR-RFLP assay. No statistically significant difference in the overall genotype frequencies or allele frequencies between cases and controls was observed. Among NPC patients, no statistical significant difference in p53 genotype frequencies between sex, histological types and clinical stages was observed. When cases and controls were categorized into 3 groups of age, >40, >45 and >50 years, the frequencies of p53 genotype in the cases were significantly different from those of the controls (P<0.05). The p53 Pro homozygotes with age of >40 years had twofold to threefold higher risk to develop NPC and the risk was increased with age (Odds Ratio (OR) increased from 2.01 to 2.63 by age >40 to >50 years). Individuals of age >40, >45 and >50 years with an Arg/Arg genotype and of age >45 and >50 years with combined Arg/Arg or Arg/Pro genotype had lower risk to develop NPC than those with Pro/Pro genotype (P<0.05). Collectively, we suggest that the p53 gene polymorphism may associate with NPC susceptibility in Thai population, particularly the Pro/Pro genotype carriers with age of >40 years. The detection of this p53 polymorphism may be a useful tool for screening of early stage and diagnosis of NPC.
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Affiliation(s)
- Danai Tiwawech
- Research Division, National Cancer Institute, Bangkok 10400, Thailand
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Suzuki K, Matsui H, Ohtake N, Nakata S, Takei T, Nakazato H, Okugi H, Koike H, Ono Y, Ito K, Kurokawa K, Yamanaka H. A p53 codon 72 polymorphism associated with prostate cancer development and progression in Japanese. J Biomed Sci 2003; 10:430-5. [PMID: 12824702 DOI: 10.1007/bf02256434] [Citation(s) in RCA: 49] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/08/2002] [Accepted: 02/20/2003] [Indexed: 01/10/2023] Open
Abstract
An association between the Pro/Pro genotype of p53 codon 72 and a lower risk of prostate cancer in Caucasians was recently reported. However, the association of this polymorphism with prostate cancer risk in a Japanese population has not been clarified. We performed a case-control study consisting of 114 prostate cancer patients and 105 noncancer controls. Sixty-nine percent (79 of 114) of the patients had a positive family history. The genotypic frequencies in the controls were 39.0% for Arg/Arg, 54.3% for Arg/Pro and 6.7% for Pro/Pro; they were in Hardy-Weinberg equilibrium. When a comparison of the distribution of the p53 codon 72 polymorphism was made between patients with a first-degree family history and all control subjects, the adjusted odds ratios (ORs) for prostate cancer associated with the Arg/Arg, Arg/Pro and Pro/Pro genotypes were 1.00, 0.99 [95% confidence interval (CI) 0.53-1.88] and 2.80 (95% CI 1.04-7.53), respectively. When stratification of cases was performed based on clinical stage (localized or metastatic cancer) and pathological grade (a Gleason score of <7 or > or =7), there tended to be a greater number of patients with localized cancers among those patients with the Arg/Pro genotype than among those with the Arg/Arg genotype (overall cases: age-adjusted OR 0.36, 95% CI 0.13-1.00, p = 0.049; positive family history cases: age-adjusted OR 0.25, 95% CI 0.075-0.84, p = 0.025). In addition, there tended to be a greater number of patients with low-grade cancers among those with the Pro/Pro genotype than among those with other genotypes (overall cases: age-adjusted OR 0.41, 95% CI 0.13-1.30, p = 0.13; positive family history cases: age-adjusted OR 0.20, 95% CI 0.004-0.89, p = 0.035). The present findings suggest that the Pro/Pro genotype of p53 codon 72 played a role in prostate cancer susceptibility in a Japanese population. However, the Pro allele did not appear to worsen such clinical parameters as clinical stage or pathological grade.
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Affiliation(s)
- Kazuhiro Suzuki
- Department of Urology, Gunma University School of Medicine, Maebashi, Gunma, Japan.
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Abstract
The tumor suppressor gene TP53 (p53) is the most extensively studied gene involved in human cancers. More than 1,400 publications have reported mutations of this gene in 150 cancer types for a total of 14,971 mutations. To exploit this huge bulk of data, specific analytic tools were highly warranted. We therefore developed a locus-specific database software called UMD-p53. This database compiles all somatic and germline mutations as well as polymorphisms of the TP53 gene which have been reported in the published literature since 1989, or unpublished data submitted to the database curators. The database is available at www.umd.necker.fr or at http://p53.curie.fr/. In this paper, we describe recent developments of the UMD-p53 database. These developments include new fields and routines. For example, the analysis of putative acceptor or donor splice sites is now automated and gives new insight for the causal role of "silent mutations." Other routines have also been created such as the prescreening module, the UV module, and the cancer distribution module. These new improvements will help users not only for molecular epidemiology and pharmacogenetic studies but also for patient-based studies. To achieve theses purposes we have designed a procedure to check and validate data in order to reach the highest quality data.
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Affiliation(s)
- Christophe Béroud
- Laboratoire de Génétique Moléculaire, CHU de Montpellier, Institut Universitaire de Recherche Clinique, Montpellier Cedex, France.
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Shen H, Zheng Y, Sturgis EM, Spitz MR, Wei Q. P53 codon 72 polymorphism and risk of squamous cell carcinoma of the head and neck: a case-control study. Cancer Lett 2002; 183:123-30. [PMID: 12065086 DOI: 10.1016/s0304-3835(02)00117-9] [Citation(s) in RCA: 72] [Impact Index Per Article: 3.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/27/2022]
Abstract
p53 plays an important role in cell-cycle control, as it facilitates DNA repair activities in response to DNA damage. An aberrant cell cycle impairs DNA repair and increases the probability of mutations that lead to carcinogenesis. The p53 codon 72 Arg/Pro polymorphism has been suggested to be associated with susceptibility to tobacco-related cancers, but this association remains controversial. In this hospital-based case-control study of 304 patients newly diagnosed with squamous cell carcinoma of the head and neck (SCCHN) and 333 cancer-free controls, we evaluated the association between this p53 polymorphism and the risk of SCCHN. All subjects were non-Hispanic whites, and the controls were frequency-matched to the cases by age (+/-5 years), sex and smoking status. Our results suggested that there was no difference in the distributions of p53 codon 72 genotypes between cases and controls (odds ratio (OR)=1.04, 95% confidence interval (CI) 0.75-1.44 for Pro/Pro vs. Arg/Arg and OR=1.01, 95% CI 0.54-1.91 for Arg/Pro vs. Arg/Arg). However, there was evidence that the Pro allele was associated with an early age of onset of SCCHN. The median ages of onset of SCCHN were 59, 56 and 53 years for Arg/Arg, Arg/Pro and Pro/Pro cases, respectively (P=0.151 among three genotypes; P=0.057 for Pro/Pro and Arg/Pro combined vs. Arg/Arg). The median ages at onset of oral cancers were 62, 57 and 51 years for Arg/Arg, Arg/Pro and Pro/Pro, respectively (P=0.091 among three genotypes; P=0.046 for Pro/Pro vs. Arg/Arg; P=0.066 for Pro/Pro and Arg/Pro combined vs. Arg/Arg). While the results suggest that the P53 codon 72 polymorphism may contribute to oral cancer susceptibility, larger studies are needed to confirm these findings.
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Affiliation(s)
- Hongbing Shen
- Department of Epidemiology, The University of Texas M.D. Anderson Cancer Center, Houston, TX 77030, USA
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