Association between the ERCC5 Asp1104His Polymorphism and Cancer Risk: A Meta-Analysis

• Published in: PloS one Vol. 7; no. 7; p. e36293
• Main Authors: Zhu, Mei-Ling, Wang, Mengyun, Cao, Zhi-Gang, He, Jing, Shi, Ting-Yan, Xia, Kai-Qin, Qiu, Li-Xin, Wei, Qing-Yi
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 18.07.2012; Public Library of Science (PLoS)
• Subjects: Amino acids; Biology; Bladder cancer; Cancer; Cancer research; Colorectal cancer; Correlation; Correlation analysis; Deoxyribonucleic acid; Disease susceptibility; DNA; DNA damage; DNA repair; DNA-Binding Proteins - genetics; Endonucleases - genetics; Epidemiology; Esophageal cancer; Gene expression; Gene Expression Regulation, Neoplastic; Gene polymorphism; Genes; Genetic aspects; Genetic Predisposition to Disease - genetics; Genetics; Genomes; Health aspects; Health risks; Heterogeneity; Human subjects; Humans; Laboratories; Lesions; Liver cancer; Medical ethics; Medical research; Medicine; Meta-analysis; Minority & ethnic groups; Mutation; Neoplasms - genetics; Nuclear Proteins - genetics; Oncology; Polymorphism; Polymorphism, Single Nucleotide; Population studies; Prostate cancer; Proteins; Repair; Risk analysis; Risk factors; RNA; RNA polymerase; RNA, Messenger - genetics; RNA, Messenger - metabolism; Single nucleotide polymorphisms; Single-nucleotide polymorphism; Transcription Factors - genetics; Ultraviolet radiation; China
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0036293

Excision repair cross complementing group 5 (ERCC5 or XPG) plays an important role in regulating DNA excision repair, removal of bulky lesions caused by environmental chemicals or UV light. Mutations in this gene cause a rare autosomal recessive syndrome, and its functional single nucleotide polymorphisms (SNPs) may alter DNA repair capacity phenotype and cancer risk. However, a series of epidemiological studies on the association between the ERCC5 Asp1104His polymorphism (rs17655, G>C) and cancer susceptibility generated conflicting results. To derive a more precise estimation of the association between the ERCC5 Asp1104His polymorphism and overall cancer risk, we performed a meta-analysis of 44 published case-control studies, in which a total of 23,490 cases and 27,168 controls were included. To provide additional biological plausibility, we also assessed the genotype-gene expression correlation from the HapMap phase II release 23 data with 270 individuals from 4 ethnic populations. When all studies were pooled, we found no statistical evidence for a significantly increased cancer risk in the recessive genetic models (His/His vs. Asp/Asp: OR = 0.99, 95% CI: 0.92-1.06, P = 0.242 for heterogeneity or His/His vs. Asp/His + Asp/Asp: OR = 0.98, 95% CI: 0.93-1.03, P = 0.260 for heterogeneity), nor in further stratified analyses by cancer type, ethnicity, source of controls and sample size. In the genotype-phenotype correlation analysis from 270 individuals, we consistently found no significant correlation of the Asp1104His polymorphism with ERCC5 mRNA expression. This meta-analysis suggests that it is unlikely that the ERCC5 Asp1104His polymorphism may contribute to individual susceptibility to cancer risk.