Abstract B30: Polymorphisms in XRCC1, ERCC4, ERCC1, and ERCC2 DNA repair genes and cervical cancer risk in Indian population.

Abstract

Abstract Background: Infection with certain types of human papillomaviruses (HPV) is highly associated with carcinomas of the human uterine cervix. However, HPV infection alone does not appear to be sufficient for the process of malignant transformation, suggesting the requirement of additional cellular events. Genetic polymorphisms in DNA repair genes is one such mechanism which may influence individual variation in DNA repair capacity and which in turn may be associated with a higher risk of developing cancer. Since studies on the association between DNA repair gene polymorphisms and cervical cancer risk appear to be very limited in Indian population, this study was designed to examine the polymorphisms associated with four DNA repair genes, namely: XRCC1(Arg194Trp, Arg399Gln and Arg280His), ERCC1 Asp118Asp, ERCC2 Lys751Gln and ERCC4 Arg415Gln and investigate their role as susceptibility markers for cervical cancer. Methods: In this ongoing population based case-control study we collected tissue and blood samples from both healthy and cervical cancer patients with different histological subtypes in the age group 18–70 years. Polymorphism for genes was genotyped by PCR-RFLP and DNA sequencing techniques. Results: Our data showed a positive association between the polymorphisms of codons 194 (p<0.001, OR=146.7, 95% CI=15.23_3528.16 for Trp allele), 399(p<0.001, OR=60, 95% CI=6.84_1354.9 for Gln allele) and 280(p=0.006, OR=0.51, 95%CI=1.88–21.99) and cervical cancer risk. Positive correlation was also found in ERCC4 Gln415Gln(p<0.001, OR=6.31, 95%CI=1.88–21.99). On the other hand, individuals homozygous for the ERCC1 18Asp allele presented no risk of developing cervical cancer(p=0.36, OR = 6.31, 95% CI=1.88–21.99) except for individuals carriers of 118Asp/Asp genotype and without family history of cancer (OR = 0.57; 95%CI = 0.33–0.98) and no association was found between ERCC2 Gln751Gln polymorphism and cervical cancer risk (p=0.48, OR=1.90, 95%CI=0.41–8.80). Compared with those individuals who didn't express any putative risk genotypes, individuals featuring all of the putative risk genotypes did experience a significantly greater cancer risk (OR = 2.43, 95% CI=1.21–4.90), particularly for HPV16 positive individuals (p=0.003, OR=4.5, 95%CI=1.45–14.63). Conclusion: In conclusion, we analysed the association between XRCC1, ERCC4, ERCC1, and ERCC2 polymorphisms and the individual susceptibility to develop cervical cancer in the Indian population, specifically in HPV16 positive population. We attempt to contribute to the discovery of which biomarkers of DNA repair capacity are useful for screening this high-risk population for primary preventing and early detection of cervical cancer. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the AACR-NCI-EORTC International Conference: Molecular Targets and Cancer Therapeutics; 2011 Nov 12-16; San Francisco, CA. Philadelphia (PA): AACR; Mol Cancer Ther 2011;10(11 Suppl):Abstract nr B30.