title: Single nucleotide polymorphisms in the DNA repair genes in HPV-positive cervical cancer.
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.
authors: Departments of aBiochemistry bBiostatistics cObstetrics and Gynaecology, All India Institute of Medical Sciences, New Delhi, India.
authors: Deepti
authors: D
authors: Bajpai
authors: Ayan
authors: A
authors: Banerjee
authors: Sujata
authors: S
authors: Pathak
authors: Bhaskar
authors: B
authors: Thakur
authors: Sunesh K
authors: SK
authors: Jain
authors: Neeta
authors: N
authors: Singh
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D002294:Carcinoma, Squamous Cell / Q000235:genetics* / Q000821:virology; D016022:Case-Control Studies; D045643:DNA Repair Enzymes / Q000235:genetics*; D004268:DNA-Binding Proteins / Q000235:genetics; D004720:Endonucleases / Q000235:genetics; D005260:Female; D005500:Follow-Up Studies; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D008875:Middle Aged; D016017:Odds Ratio; D027383:Papillomaviridae / Q000235:genetics*; D030361:Papillomavirus Infections / Q000235:genetics* / Q000821:virology; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D011379:Prognosis; D065310:Squamous Intraepithelial Lesions of the Cervix / Q000235:genetics* / Q000821:virology; D002583:Uterine Cervical Neoplasms / Q000235:genetics* / Q000821:virology; D000076105:X-ray Repair Cross Complementing Protein 1; D051759:Xeroderma Pigmentosum Group D Protein / Q000235:genetics; D055815:Young Adult
chemical_list: D004268:DNA-Binding Proteins; D000076105:X-ray Repair Cross Complementing Protein 1; C000619371:XRCC1 protein, human; C095888:xeroderma pigmentosum group F protein; C071447:ERCC1 protein, human; D004720:Endonucleases; D051759:Xeroderma Pigmentosum Group D Protein; C497292:ERCC2 protein, human; D045643:DNA Repair Enzymes