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Ghaderi-Zefrehi H, Rezaei M, Sadeghi F, Heiat M. Genetic polymorphisms in DNA repair genes and hepatocellular carcinoma risk. DNA Repair (Amst) 2021; 107:103196. [PMID: 34416543 DOI: 10.1016/j.dnarep.2021.103196] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/11/2020] [Revised: 05/23/2021] [Accepted: 07/26/2021] [Indexed: 01/27/2023]
Abstract
Hepatocellular carcinoma (HCC) is one of the most frequent types of tumors worldwide. Its occurrence and development have been related to various risk factors, such as chronic infection with hepatitis B or C viruses and alcohol addiction. DNA repair systems play a critical role in maintaining the integrity of the genome. Defects in these systems have been related to increased susceptibility to various types of cancer. Multiple genetic polymorphisms in genes of DNA repair systems have been reported that may affect DNA repair capacity (DRC) and modulate risk to cancer. Several studies have been conducted to assess the role of polymorphisms of DNA repair genes on the HCC risk. Identifying these polymorphisms and their association with HCC risk may help to improve prevention and treatment strategies. In this study, we review investigations that evaluated the association between genetic polymorphisms of DNA repair genes and risk of HCC.
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Affiliation(s)
- Hossein Ghaderi-Zefrehi
- Department of Clinical Biochemistry, Faculty of Medicine, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran; Baqiyatallah Research Center for Gastroenterology and Liver Diseases, Baqiyatallah University of Medical Sciences, Tehran, Iran
| | - Maryam Rezaei
- Department of Clinical Biochemistry, School of Medicine, Hamadan University of Medical Sciences, Hamadan, Iran
| | - Farzin Sadeghi
- Cellular and Molecular Biology Research Center, Health Research Institute, Babol University of Medical Sciences, Babol, Iran
| | - Mohammad Heiat
- Baqiyatallah Research Center for Gastroenterology and Liver Diseases, Baqiyatallah University of Medical Sciences, Tehran, Iran.
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Li YK, Xu Q, Sun LP, Gong YH, Jing JJ, Xing CZ, Yuan Y. Nucleotide excision repair pathway gene polymorphisms are associated with risk and prognosis of colorectal cancer. World J Gastroenterol 2020; 26:307-323. [PMID: 31988591 PMCID: PMC6969885 DOI: 10.3748/wjg.v26.i3.307] [Citation(s) in RCA: 19] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/12/2019] [Revised: 12/26/2019] [Accepted: 01/01/2020] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND Single nucleotide polymorphisms (SNPs) are universally present in nucleotide excision repair (NER) pathway genes, which could make impacts on colorectal carcinogenesis and prognosis.
AIM To explore the association of all tagSNPs in NER pathway genes with colorectal cancer (CRC) risk and prognosis in a northern Chinese population by a two-stage case-control design composed of a discovery and validation stage.
METHODS Genotyping for NER SNPs was performed using kompetitive allele specific PCR. In the discovery stage, 39 tagSNPs in eight genes were genotyped in 368 subjects, including 184 CRC cases and 184 individual-matched controls. In the validation stage, 13 SNPs in six genes were analyzed in a total of 1712 subjects, including 854 CRC cases and 858 CRC-free controls.
RESULTS Two SNPs (XPA rs10817938 and XPC rs2607775) were associated with an increased CRC risk in overall and stratification analyses. Significant cumulative and interaction effects were also demonstrated in the studied SNPs on CRC risk. Another two SNPs (ERCC2 rs1052555 and ERCC5 rs2228959) were newly found to be associated with a poor overall survival of CRC patients.
CONCLUSION Our findings suggest novel SNPs in NER pathway genes that can be predictive for CRC risk and prognosis in a large-scale Chinese population. The present study has referential values for the identification of all-round NER-based genetic biomarkers in predicting the susceptibility and clinical outcome of CRC.
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Affiliation(s)
- Yan-Ke Li
- Tumor Etiology and Screening Department of Cancer Institute and General Surgery, Key Laboratory of Cancer Etiology and Prevention of Liaoning Education Department, Key Laboratory of GI Cancer Etiology and Prevention of Liaoning Province, the First Hospital of China Medical University, Shenyang 110001, Liaoning Province, China
- Department of Anorectal Surgery, the First Hospital of China Medical University, Shenyang 110001, Liaoning Province, China
| | - Qian Xu
- Tumor Etiology and Screening Department of Cancer Institute and General Surgery, Key Laboratory of Cancer Etiology and Prevention of Liaoning Education Department, Key Laboratory of GI Cancer Etiology and Prevention of Liaoning Province, the First Hospital of China Medical University, Shenyang 110001, Liaoning Province, China
| | - Li-Ping Sun
- Tumor Etiology and Screening Department of Cancer Institute and General Surgery, Key Laboratory of Cancer Etiology and Prevention of Liaoning Education Department, Key Laboratory of GI Cancer Etiology and Prevention of Liaoning Province, the First Hospital of China Medical University, Shenyang 110001, Liaoning Province, China
| | - Yue-Hua Gong
- Tumor Etiology and Screening Department of Cancer Institute and General Surgery, Key Laboratory of Cancer Etiology and Prevention of Liaoning Education Department, Key Laboratory of GI Cancer Etiology and Prevention of Liaoning Province, the First Hospital of China Medical University, Shenyang 110001, Liaoning Province, China
| | - Jing-Jing Jing
- Tumor Etiology and Screening Department of Cancer Institute and General Surgery, Key Laboratory of Cancer Etiology and Prevention of Liaoning Education Department, Key Laboratory of GI Cancer Etiology and Prevention of Liaoning Province, the First Hospital of China Medical University, Shenyang 110001, Liaoning Province, China
| | - Cheng-Zhong Xing
- Tumor Etiology and Screening Department of Cancer Institute and General Surgery, Key Laboratory of Cancer Etiology and Prevention of Liaoning Education Department, Key Laboratory of GI Cancer Etiology and Prevention of Liaoning Province, the First Hospital of China Medical University, Shenyang 110001, Liaoning Province, China
- Department of Anorectal Surgery, the First Hospital of China Medical University, Shenyang 110001, Liaoning Province, China
| | - Yuan Yuan
- Tumor Etiology and Screening Department of Cancer Institute and General Surgery, Key Laboratory of Cancer Etiology and Prevention of Liaoning Education Department, Key Laboratory of GI Cancer Etiology and Prevention of Liaoning Province, the First Hospital of China Medical University, Shenyang 110001, Liaoning Province, China
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Yuan M, Yu C, Yu K. Association of human XPA rs1800975 polymorphism and cancer susceptibility: an integrative analysis of 71 case-control studies. Cancer Cell Int 2020; 20:164. [PMID: 32435155 PMCID: PMC7218628 DOI: 10.1186/s12935-020-01244-5] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/03/2019] [Accepted: 05/07/2020] [Indexed: 12/13/2022] Open
Abstract
BACKGROUND The objective of the present study is to comprehensively evaluate the impact of the rs1800975 A/G polymorphism within the human xeroderma pigmentosum group A (XPA) gene on susceptibility to overall cancer by performing an integrative analysis of the current evidence. METHODS We retrieved possible relevant publications from a total of six electronic databases (updated to April 2020) and selected eligible case-control studies for pooled assessment. P-values of association and odds ratio (OR) were calculated for the assessment of association effect. We also performed Begg's test and Egger's test, sensitivity analysis, false-positive report probability (FPRP) analysis, trial sequential analysis (TSA), and expression/splicing quantitative trait loci (eQTL/sQTL) analyses. RESULTS In total, 71 case-control studies with 19,257 cases and 30,208 controls from 52 publications were included for pooling analysis. We observed an enhanced overall cancer susceptibility in cancer cases compared with negative controls in the Caucasian subgroup analysis for the genetic models of allelic G vs. A, carrier G vs. A, homozygotic GG vs AA, heterozygotic AG vs. AA, dominant AG + GG vs. AA and recessive GG vs. AA + AG (P < 0.05, OR > 1). A similar positive conclusion was also detected in the "skin cancer" or "skin basal cell carcinoma (BCC)" subgroup analysis of the Caucasian population. Our FPRP analysis and TSA results further confirmed the robustness of the conclusion. However, our eQTL/sQTL data did not support the strong links of rs1800975 with the gene expression or splicing changes of XPA in the skin tissue. In addition, even though we observed a decreased risk of lung cancer under the homozygotic, heterozygotic and dominant models (P < 0.05, OR < 1) and an enhanced risk of colorectal cancer under the allelic, homozygotic, heterozygotic, dominant (P < 0.05, OR > 1), our data from FPRP analysis and another pooling analysis with only the population-based controls in the Caucasian population did not support the strong links between the XPA rs1800975 A/G polymorphism and the risk of lung or colorectal cancer. CONCLUSIONS Our findings provide evidence of the close relationship between the XPA rs1800975 A/G polymorphism and susceptibility to skin cancer in the Caucasian population. The potential effect of XPA rs1800975 on the risk of developing lung or colorectal cancer still merits the enrollment of larger well-scaled studies.
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Affiliation(s)
- Maoxi Yuan
- Department of Thoracic Surgery, Linyi Central Hospital, No. 17 Jiankang Road, Yishui County, Linyi, Shandong 276400 People’s Republic of China
| | - Chunmei Yu
- Department of Thoracic Surgery, Linyi Central Hospital, No. 17 Jiankang Road, Yishui County, Linyi, Shandong 276400 People’s Republic of China
| | - Kuiying Yu
- First Department of Neurology, The First Hospital of Zibo, Zibo, Shandong 255200 People’s Republic of China
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Al-Shaheri FN, Al-Shami KM, Gamal EH, Mahasneh AA, Ayoub NM. Association of DNA repair gene polymorphisms with colorectal cancer risk and treatment outcomes. Exp Mol Pathol 2019; 113:104364. [PMID: 31881200 DOI: 10.1016/j.yexmp.2019.104364] [Citation(s) in RCA: 12] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/19/2019] [Revised: 12/16/2019] [Accepted: 12/24/2019] [Indexed: 02/07/2023]
Abstract
Colorectal cancer (CRC) is the third most common carcinoma worldwide. Despite the progress in screening and treatment, CRC remains a leading cause of cancer-related mortality. Alterations to normal nucleic acid processing may drive neoplastic transformation of colorectal epithelium. DNA repair machinery performs an essential function in the protection of genome by reducing the number of genetic polymorphisms/variations that may drive carcinogenicity. Four essential DNA repair systems are known which include nucleotide excision repair (NER), base excision repair (BER), mismatch repair (MMR), and double-strand break repair (DSBR). Polymorphisms of DNA repair genes have been shown to influence the risk of cancer development as well as outcomes of treatment. Several studies demonstrated the association between genetic polymorphism of DNA repair genes and increased risk of CRC in different populations. In this review, we have summarized the impact of DNA repair gene polymorphisms on risk of CRC development and treatment outcomes. Advancements of the current understanding for the impact of DNA repair gene polymorphisms on the risk and treatment of CRC may support diagnostic and predictive roles in patients with CRC.
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Affiliation(s)
- Fawaz N Al-Shaheri
- Division of Functional Genome Analysis, German Cancer Research Center (DKFZ), ImNeuenheimer Feld 580, 69120 Heidelberg, Germany; Medical Faculty Heidelberg, University of Heidelberg, ImNeuenheimer Feld 672, 69120 Heidelberg, Germany; Faculty of Applied Medical Sciences, Department of Medical Laboratory Sciences, Jordan University of Science and Technology, Irbid, Jordan.
| | - Kamal M Al-Shami
- Department of Drug Discovery and Development, Harrison School of Pharmacy, Auburn University, 720 South Donahue Drive, Auburn, Alabama 36849, United States of America; Department of Clinical Pharmacy, Faculty of Pharmacy, Jordan University of Science and Technology, Irbid 22110, Jordan.
| | - Eshrak H Gamal
- Department of Oncology, Collage of Medicine, Bonn University, Germany; Faculty of Applied Medical Sciences, Department of Medical Laboratory Sciences, Jordan University of Science and Technology, Irbid, Jordan.
| | - Amjad A Mahasneh
- Department of Applied Biological Sciences, Faculty of Science and Arts, Jordan University of Science and Technology, Irbid 22110, Jordan.
| | - Nehad M Ayoub
- Department of Clinical Pharmacy, Faculty of Pharmacy, Jordan University of Science and Technology, Irbid 22110, Jordan.
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Tian J, Liu C, Liu G, Zuo C, Chen H. Cumulative evidence for association between genetic polymorphisms and esophageal cancer susceptibility: A review with evidence from meta-analysis and genome-wide association studies. Cancer Med 2019; 8:1289-1305. [PMID: 30793520 PMCID: PMC6434199 DOI: 10.1002/cam4.1972] [Citation(s) in RCA: 15] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/26/2018] [Revised: 11/27/2018] [Accepted: 12/21/2018] [Indexed: 12/16/2022] Open
Abstract
An increasing number of publications had reported the association between single‐nucleotide polymorphisms (SNPs) and esophageal cancer (EC) risk in the past decades. Results from these publications were controversial. We used PubMed, Medline, and Web of Science to identify meta‐analysis articles published before 30 July 2018, that summarize a comprehensive investigation for cumulative evidence of genetic polymorphisms of EC and its subtype risk. Two methods, Venice criteria and false‐positive report probability (FPRP) tests, were used to assess cumulative evidence of significant associations. At last, 107 meta‐analyses were considered to be in conformity with the inclusion criteria, yielding 51 variants associated with EC or esophageal squamous cell carcinoma (ESCC). Thirty‐eight variants were considered to be nominally significant associated with risk of EC or ESCC, whereas the rest showed non‐association. In additional, five variants on five genes were rated as strong cumulative epidemiological evidence for a nominally significant association with EC and ESCC risk, including CYP1A1 rs1048943, EGF rs444903, HOTAIR rs920778, MMP2 rs243865, and PLCE1 rs2274223, 10 variants were rated as moderate, and 18 variants were rated as weak. Additionally, 17 SNPs were verified noteworthy in six genomewide association studies (GWAS) using FPRP methods. Collectively, this review offered a comprehensively referenced information with cumulative evidence of associations between genetic polymorphisms and EC and ESCC risk.
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Affiliation(s)
- Jie Tian
- Department of Cardiothoracic Surgery, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China
| | - Caiyang Liu
- Department of Cardiothoracic Surgery, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China
| | - Guanchu Liu
- Department of Cardiothoracic Surgery, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China
| | - Chunjian Zuo
- Department of Cardiothoracic Surgery, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China
| | - Huanwen Chen
- Department of Cardiothoracic Surgery, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China
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Feng X, Liu J, Gong Y, Gou K, Yang H, Yuan Y, Xing C. DNA repair protein XPA is differentially expressed in colorectal cancer and predicts better prognosis. Cancer Med 2018; 7:2339-2349. [PMID: 29675892 PMCID: PMC6010851 DOI: 10.1002/cam4.1480] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/07/2017] [Revised: 03/04/2018] [Accepted: 03/13/2018] [Indexed: 12/14/2022] Open
Abstract
As an indispensable factor in DNA damage recognition step of nucleotide excision repair, XPA interacts with a series of proteins to initiate repair process. The expression characteristics of XPA in colorectal cancer (CRC) and its influence on CRC prognosis remain elusive. Tissue specimens of CRC and nontumor adjacent tissues from 283 patients were collected. XPA protein expressions were detected by immunohistochemistry staining. Nonparametric test was used to investigate the difference of XPA expression between CRC and nontumor adjacent tissues, as well as the correlation between XPA expression and clinicopathological parameters of CRC. Univariate and multivariate Cox proportional hazards models were applied to estimate the relationship between XPA expression and CRC prognosis. Meanwhile, we analyzed TCGA data to investigate the relation between XPA mRNA expression and survival of CRC. XPA protein expression was significantly decreased in CRC tissues compared with nontumor adjacent tissues (P = 0.001). Subgroup analysis indicated consistently significant down-regulation of XPA in CRC tissues in age > 60 (P = 0.026), age ≤ 60 (P = 0.008), colon cancer (P = 0.009), and rectal cancer (P = 0.015) patients and males (P = 0.004). For clinicopathological parameters, CRC patients with drinking habits revealed XPA overexpression than nondrinkers (P = 0.032). For prognosis, CRC patients with high XPA protein expression had longer overall survival (OS) (HR = 0.62, 95%CI: 0.39-0.97, P = 0.037). Stratified analysis suggested a better prognosis in relation to high XPA protein expression in patients over 60 years (adjusted HR = 0.48, P = 0.021), with rectal cancer (HR = 0.56, P = 0.037), without distant metastasis (HR = 0.58, P = 0.033), without tumor deposits (HR = 0.40, P = 0.006; adjusted HR = 0.44, P = 0.028), and with tumor diameter over 4 cm (HR = 0.49, P = 0.023). DNA repair protein XPA is significantly decreased in colorectal cancer tissues than in adjacent nontumor tissues. High expression of XPA protein showed significant relationship with better survival of CRC, especially rectal cancer. XPA might be a novel biomarker but might not be an independent factor to predict prognosis of CRC patients.
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Affiliation(s)
- Xue Feng
- Tumor Etiology and Screening Department of Cancer Institute and General SurgeryThe First Hospital of China Medical UniversityShenyang110001China
- Liaoning Provincial Education DepartmentKey Laboratory of Cancer Etiology and PreventionChina Medical UniversityShenyang110001China
| | - Jingwei Liu
- Tumor Etiology and Screening Department of Cancer Institute and General SurgeryThe First Hospital of China Medical UniversityShenyang110001China
- Liaoning Provincial Education DepartmentKey Laboratory of Cancer Etiology and PreventionChina Medical UniversityShenyang110001China
| | - Yuehua Gong
- Tumor Etiology and Screening Department of Cancer Institute and General SurgeryThe First Hospital of China Medical UniversityShenyang110001China
- Liaoning Provincial Education DepartmentKey Laboratory of Cancer Etiology and PreventionChina Medical UniversityShenyang110001China
| | - Kaihua Gou
- Tumor Etiology and Screening Department of Cancer Institute and General SurgeryThe First Hospital of China Medical UniversityShenyang110001China
- Liaoning Provincial Education DepartmentKey Laboratory of Cancer Etiology and PreventionChina Medical UniversityShenyang110001China
| | - Huaiwei Yang
- Tumor Etiology and Screening Department of Cancer Institute and General SurgeryThe First Hospital of China Medical UniversityShenyang110001China
- Liaoning Provincial Education DepartmentKey Laboratory of Cancer Etiology and PreventionChina Medical UniversityShenyang110001China
| | - Yuan Yuan
- Tumor Etiology and Screening Department of Cancer Institute and General SurgeryThe First Hospital of China Medical UniversityShenyang110001China
- Liaoning Provincial Education DepartmentKey Laboratory of Cancer Etiology and PreventionChina Medical UniversityShenyang110001China
| | - Chengzhong Xing
- Tumor Etiology and Screening Department of Cancer Institute and General SurgeryThe First Hospital of China Medical UniversityShenyang110001China
- Liaoning Provincial Education DepartmentKey Laboratory of Cancer Etiology and PreventionChina Medical UniversityShenyang110001China
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Kamiza AB, Hsieh L, Tang R, Chien H, Lai C, Chiu L, Lo T, Hung K, You J, Wang W, Hsiung CA, Yeh C. Polymorphisms of DNA repair genes are associated with colorectal cancer in patients with Lynch syndrome. Mol Genet Genomic Med 2018; 6:533-540. [PMID: 29664240 PMCID: PMC6081223 DOI: 10.1002/mgg3.402] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/02/2017] [Revised: 02/04/2018] [Accepted: 03/12/2018] [Indexed: 12/16/2022] Open
Abstract
BACKGROUND DNA repair genes are crucial for maintaining genomic stability by preventing mutagenesis and carcinogenesis. The present retrospective cohort study aimed at investigating whether MLH1, APEX1, MUTYH, OGG1, NUDT1, XRCC5, XPA, and ERCC2 single nucleotide polymorphisms (SNPs) are associated with colorectal cancer (CRC) in Chinese population with Lynch syndrome. METHODS From Amsterdam criteria family registry, we identified 270 patients with Lynch syndrome. Hazard ratios (HRs) and 95% confidence intervals (CIs) for the association between DNA repair SNPs and CRC were calculated using a weighted Cox proportional hazard regression model. RESULTS Heterozygous variants of rs1799832 in NUDT1 (HR = 2.97, 95% CI = 1.51-5.83) and rs13181 in ERCC2 (HR = 2.69, 95% CI = 1.10-6.55) were significantly associated with an increased risk of CRC compared with wild-type homozygous CC and TT genotypes, respectively. However, the variant CG+GG genotype of MUTYH rs3219489 was associated with a decreased risk of CRC (HR = 0.49, 95% CI = 0.26-0.91) compared with the homozygous CC wild-type counterparts. CONCLUSION Our findings revealed that polymorphisms of DNA repair genes that include NUDT1, ERCC2, and MUTYH are associated with CRC in patients with Lynch syndrome in Chinese population. Further studies with large sample size are needed to confirm our findings.
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Affiliation(s)
- Abram B. Kamiza
- School of Public HealthCollege of Public HealthTaipei Medical UniversityTaipeiTaiwan
| | - Ling‐Ling Hsieh
- Department of Public HealthCollege of MedicineChang Gung UniversityTaoyuanTaiwan
| | - Reiping Tang
- Colorectal SectionDepartment of SurgeryChang Gung Memorial HospitalTaoyuanTaiwan
- School of MedicineChang Gung UniversityTaoyuanTaiwan
| | - Huei‐Tzu Chien
- Department of Public HealthCollege of MedicineChang Gung UniversityTaoyuanTaiwan
- Department of Nutrition and Health SciencesChang Gung University of Science and TechnologyTaoyuanTaiwan
| | - Chih‐Hsiung Lai
- Department of Public HealthCollege of MedicineChang Gung UniversityTaoyuanTaiwan
| | - Li‐Ling Chiu
- Department of Public HealthCollege of MedicineChang Gung UniversityTaoyuanTaiwan
- Department of Nutrition and Health SciencesChang Gung University of Science and TechnologyTaoyuanTaiwan
| | - Tsai‐Ping Lo
- Institute of Population Health SciencesNational Health Research InstitutesMiaoliTaiwan
| | - Kuan‐Yi Hung
- Institute of Population Health SciencesNational Health Research InstitutesMiaoliTaiwan
| | - Jeng‐Fu You
- Colorectal SectionDepartment of SurgeryChang Gung Memorial HospitalTaoyuanTaiwan
- School of MedicineChang Gung UniversityTaoyuanTaiwan
| | - Wen‐Chang Wang
- Ph.D. Program for Translational MedicineCollege of Medical Science and TechnologyTaipei Medical UniversityTaipeiTaiwan
| | - Chao A. Hsiung
- Institute of Population Health SciencesNational Health Research InstitutesMiaoliTaiwan
| | - Chih‐Ching Yeh
- School of Public HealthCollege of Public HealthTaipei Medical UniversityTaipeiTaiwan
- Department of Public HealthChina Medical UniversityTaichungTaiwan
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Martorell-Marugan J, Toro-Dominguez D, Alarcon-Riquelme ME, Carmona-Saez P. MetaGenyo: a web tool for meta-analysis of genetic association studies. BMC Bioinformatics 2017; 18:563. [PMID: 29246109 PMCID: PMC5732412 DOI: 10.1186/s12859-017-1990-4] [Citation(s) in RCA: 90] [Impact Index Per Article: 11.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/09/2017] [Accepted: 12/06/2017] [Indexed: 11/26/2022] Open
Abstract
Background Genetic association studies (GAS) aims to evaluate the association between genetic variants and phenotypes. In the last few years, the number of this type of study has increased exponentially, but the results are not always reproducible due to experimental designs, low sample sizes and other methodological errors. In this field, meta-analysis techniques are becoming very popular tools to combine results across studies to increase statistical power and to resolve discrepancies in genetic association studies. A meta-analysis summarizes research findings, increases statistical power and enables the identification of genuine associations between genotypes and phenotypes. Meta-analysis techniques are increasingly used in GAS, but it is also increasing the amount of published meta-analysis containing different errors. Although there are several software packages that implement meta-analysis, none of them are specifically designed for genetic association studies and in most cases their use requires advanced programming or scripting expertise. Results We have developed MetaGenyo, a web tool for meta-analysis in GAS. MetaGenyo implements a complete and comprehensive workflow that can be executed in an easy-to-use environment without programming knowledge. MetaGenyo has been developed to guide users through the main steps of a GAS meta-analysis, covering Hardy-Weinberg test, statistical association for different genetic models, analysis of heterogeneity, testing for publication bias, subgroup analysis and robustness testing of the results. Conclusions MetaGenyo is a useful tool to conduct comprehensive genetic association meta-analysis. The application is freely available at http://bioinfo.genyo.es/metagenyo/. Electronic supplementary material The online version of this article (10.1186/s12859-017-1990-4) contains supplementary material, which is available to authorized users.
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Affiliation(s)
| | - Daniel Toro-Dominguez
- Bioinformatics Unit, Centre for Genomics and Oncological Research (GENYO), Granada, Spain.,Medical Genomics, Centre for Genomics and Oncological Research (GENYO), Granada, Spain
| | - Marta E Alarcon-Riquelme
- Medical Genomics, Centre for Genomics and Oncological Research (GENYO), Granada, Spain.,Institute for Environmental Medicine, Karolinska Institutet, Stockholm, Sweden
| | - Pedro Carmona-Saez
- Bioinformatics Unit, Centre for Genomics and Oncological Research (GENYO), Granada, Spain.
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Potential risk of esophageal squamous cell carcinoma due to nucleotide excision repair XPA and XPC gene variants and their interaction among themselves and with environmental factors. Tumour Biol 2016; 37:10193-207. [PMID: 26831662 DOI: 10.1007/s13277-016-4895-3] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/09/2015] [Accepted: 01/20/2016] [Indexed: 02/07/2023] Open
Abstract
The association of nucleotide excision repair (NER) gene polymorphisms with esophageal squamous cell carcinoma (ESCC) is inconclusive. The aim of the current study was to assess the association of repair gene xeroderma pigmentosum A (XPA) (rs-1800975) and xeroderma pigmentosum C (XPC) (rs-2228000) polymorphisms with ESCC risk as well as modifying effects of environmental factors. The genotyping was done in 450 confirmed ESCC cases and equal number of individually matched controls by the polymerase chain reaction and restriction fragment length polymorphism (PCR-RFLP) and direct sequencing methods. Conditional logistic regression models were used to assess the genotypic associations and interactions. A high ESCC risk was found in subjects who carried the homozygous minor allele of XPA (odds ratio (OR) = 3.57; 95 % confidence interval (CI) = 1.76-7.23), and the risk was higher when analysis was limited to participants who were ever smokers (OR = 4.22; 95 % CI = 2.01-8.88), lived in adobe houses (OR = 8.42; 95 % CI = 3.74-18.95), consumed large volumes of salt tea (OR = 7.42; 95 % CI = 3.30-16.69), or had a positive family history of cancer (FHC) (OR = 9.47; 95 % CI = 4.67-19.20). In case of XPC, a homozygous minor allele also showed strong association with ESCC risk (OR = 4.43; 95 % CI = 2.41-8.16). We again observed a very strong effect of the above environmental factors in elevating the risk of ESCC. Further, the variant genotypes of both genes in combination showed an increased risk towards ESCC (OR = 7.01; 95 % CI = 3.14-15.64) and such association was synergistically significant. Salt tea consumption showed an interaction with genotypes of XPA and XPC. However, an interaction with FHC was significant in the case of XPA genotype only. XPA and XPC genotypes are associated with an increased risk of ESCC, and such association was reasonably modulated by different exposures.
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