Journal
EUROPEAN JOURNAL OF CANCER PREVENTION
Volume 25, Issue 3, Pages 224-231Publisher
LIPPINCOTT WILLIAMS & WILKINS
DOI: 10.1097/CEJ.0000000000000159
Keywords
cervical cancer; ERCC1; ERCC2; ERCC4; genetic susceptibility; polymorphism (genetics); XRCC1
Categories
Funding
- Indian Council of Medical Research
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Genetic variation in DNA repair genes can modulate DNA repair capacity and may be related to the risk of cancer. The human papillomavirus is considered to be a necessary but not sufficient cause for cervical cancer and, therefore, other factors contribute to the carcinogenesis. A hereditary component for this neoplasia has been reported. Evaluation of the association of six polymorphisms was carried out in the following DNA repair genes: XRCC1 (Arg194Trp, Arg280His, and Arg399Gln), ERCC1 (Asp118Asp), ERCC2 (Lys751Gln), and ERCC4 (Arg415Gln). The cases (n=110) included 65 squamous cell carcinomas (SCCs) and 45 squamous intraepithelial lesions (SIL). Controls (n=68) were recruited from among women without cervical abnormalities. Genotypes were determined by PCR-restriction fragment length polymorphism and DNA sequencing. A positive association was observed between the polymorphisms of XRCC1 genes, that is, in codons 194 [P=0.001, odds ratio (OR)=20.1, 95% confidence interval (CI)=5.9-68.8], 280 (P=0.001, OR=5.4, 95% CI=2.3-12.6), and 399 (P=0.008, OR=4.2, 95% CI=1.5-12.1) and cervical cancer. SIL patients also showed a significant association with codon 194 (P=0.012, OR=3.8, 95% CI=1.3-10.6), but not with 280 (P=0.35) and 399 (P=0.81). A positive correlation was also found in ERCC4 Gln415Gln in both SCCs and SILs (P=0.001, OR=21.3, 95% CI=7.1-64.0 and P=0.001, OR=7.8, 95% CI=2.9-20.9, respectively). For ERCC2 Gln751Gln, the association was significant for both SCCs (P=0.001, OR=10.1, 95% CI=2.6-37.9) and SILs (P=0.001, OR=8.9, 95% CI=2.8-28.3). However, the risk of SCC did not appear to differ significantly among individuals with the ERCC1 Asp118Asp genotype (P=0.404). For SILs, it appeared to be a protective genotype (95% CI=0.1-0.7). This study indicates that variant types of DNA repair genes play an important role in modifying individual susceptibility to SCC. Copyright (C) 2016 Wolters Kluwer Health, Inc. All rights reserved.
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