TY - JOUR
T1 - Single nucleotide polymorphisms in the DNA repair genes in HPV-positive cervical cancer
AU - Bajpai, Deepti
AU - Banerjee, Ayan
AU - Pathak, Sujata
AU - Thakur, Bhaskar
AU - Jain, Sunesh K.
AU - Singh, Neeta
N1 - Publisher Copyright:
Copyright © 2016 Wolters Kluwer Health, Inc. All rights reserved.
PY - 2016/4/13
Y1 - 2016/4/13
N2 - 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.
AB - 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.
KW - Cervical cancer
KW - ERCC1
KW - ERCC2
KW - ERCC4
KW - Genetic susceptibility
KW - Polymorphism (Genetics)
KW - XRCC1
UR - http://www.scopus.com/inward/record.url?scp=84962050671&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84962050671&partnerID=8YFLogxK
U2 - 10.1097/CEJ.0000000000000159
DO - 10.1097/CEJ.0000000000000159
M3 - Article
C2 - 25812040
AN - SCOPUS:84962050671
SN - 0959-8278
VL - 25
SP - 224
EP - 231
JO - European Journal of Cancer Prevention
JF - European Journal of Cancer Prevention
IS - 3
ER -