Single nucleotide polymorphisms in the DNA repair genes in HPV-positive cervical cancer

Deepti Bajpai, Ayan Banerjee, Sujata Pathak, Bhaskar Thakur, Sunesh K. Jain, Neeta Singh

Research output: Contribution to journalArticlepeer-review

12 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)224-231
Number of pages8
JournalEuropean Journal of Cancer Prevention
Volume25
Issue number3
DOIs
StatePublished - Apr 13 2016
Externally publishedYes

Keywords

  • Cervical cancer
  • ERCC1
  • ERCC2
  • ERCC4
  • Genetic susceptibility
  • Polymorphism (Genetics)
  • XRCC1

ASJC Scopus subject areas

  • Epidemiology
  • Oncology
  • Public Health, Environmental and Occupational Health
  • Cancer Research

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