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P2.007 Genetic Risk of DNA Repair Gene Polymorphisms in High- Risk HPV Associated Cervical Carcinogenesis
  1. D Bajpai,
  2. A Banerjee,
  3. S Pathak,
  4. S Jain,
  5. N Singh
  1. All India Institute of Medical Sciences, New Delhi, India

Abstract

Background Cervical cancer is the second most common cancer in women worldwide. A large number of young sexually active women get infected by human papillomavirus (HPV) but only a small fraction of them have persistent infection and develop cervical cancer pointing to co- factors including host genetics that might play a role in outcome of the HPV infection. This study was designed to examine the polymorphisms associated with four DNA repair genes, viz., XRCC1 (Arg194Trp, Arg399Gln and Arg280His), ERCC1 Asp118Asp, ERCC2 Lys751Gln and ERCC4 Arg415Gln and investigate their role as susceptibility markers for cervical precancer (LSIL & HSIL) and cancer.

Methods The cases comprised 105 patients: 65 cervical squamous cell carcinomas (SCCs), and 40 squamous intraepithelial lesions (SILs). 65 healthy women were recruited as the controls. Genotypes were determined by PCR-RFLP and DNA sequencing techniques.

Results Our data showed a positive association between the polymorphisms of codons 194 (p = 0.001, OR = 22.4, 95% CI = 9.15–55.03), 280 (p = 0.001, OR = 20.04, 95% CI = 8.4–47.5) and 399 (p = 0.001, OR = 11.11, 95% CI = 4.98–24.78) and cervical cancer. SIL patients also showed a significant association with codon 194 (p = 0.001, OR = 7.56, 95% CI = 3.42–16.70) and 280 (p = 0.015, OR = 3.05, 95% CI = 1.35–6.88) but not with 399 (p = 0.142). Positive correlation was also found in ERCC4 Gln415Gln in both SCCs and SILs (p = 0.001, OR = 5.45, 95% = 3.19–9.29 and p = 0.001, OR = 2.76, 95% = 1.55–4.91, respectively). For ERCC2 Gln751Gln the association was significant for SCCs (p = 0.010, OR = 1.44, 95% = 0.86–2.14) but not for SILs (p = 0.088). However the risk for cervical precancer and cancer did not appear to differ significantly amongst individuals featuring the ERCC1 Asp118Asp genotype (p = 0.594 and 0.080, respectively).

Conclusion We analysed the association between XRCC1, ERCC4, ERCC2 and ERCC1 polymorphisms and the individual susceptibility to develop cervical precancer and cancer. We attempt to contribute to the discovery of which biomarkers of DNA repair are useful for screening this high-risk population for primary preventing and early detection of cervical cancer.

  • cancer susceptibility
  • cervical cancer
  • DNA repair genes

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