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P10.06 Prognostic importance of dna repair gene polymorphisms in cervical cancer patients from india
  1. D Bajpai1,
  2. S Pathak1,
  3. S Jain2,
  4. N Singh1
  1. 1Department of Biochemistry, All India Institute of Medical Sciences, New Delhi, India
  2. 2Department of Obstetrics and Gynecology, All India Institute of Medical Sciences, New Delhi, India

Abstract

Background The cell’s ability to repair DNA damage is important. Genetic variation in DNA repair genes can modulate DNA repair capacity and may be related to cancer risk. Human papillomavirus (HPV) is considered to be a necessary but not sufficient cause for cervical cancer and, therefore, other factors contribute to the carcinogenic process.

Objectives To evaluate polymorphisms in the DNA repair genes: XRCC1 (Arg194Trp, Arg280His, and Arg399Gln), ERCC1 (Asp118Asp), ERCC2 (Lys751Gln) and ERCC4 (Arg415Gln) with the risk of cervical cancer progression and to analyse their expression profile.

Material and methods A case control study consisting of 178 samples [65 cervical cancer (CaCx), 45 squamous intraepithelial lesion (SIL) and 68 controls] was carried out. Genotypes were determined by PCR-RFLP and DNA sequencing. Expression analysis was done by RT-PCR and Western blotting.

Results Positive association was seen between the polymorphisms of XRCC1 genes i.e., in codons 194 (OR = 20.1, 95% CI = 5.9–68.8), 280 (OR = 5.4, 95% CI = 2.3–12.6) and 399 (OR = 4.2, 95% CI = 1.5–12.1) and cervical cancer. SIL patients also showed a significant association with codon 194 (OR = 7.56, 95% CI = 3.42–16.70). Positive correlation was also found in ERCC4 Gln415Gln in both CaCx and SILs (OR = 21.3 95% CI = 7.1–64.0 and OR = 7.8, 95% CI = 2.9–20.9, respectively). For ERCC2 Gln751Gln the association was significant for both CaCx (OR = 10.1, 95% CI = 2.6–37.9) and SILs (OR = 8.9, 95% CI = 2.8–28.3). However the risk for CaCx and SILs did not appear to differ significantly amongst individuals featuring the ERCC1 Asp118Asp genotype. The invasive cancer and SIL subjects also demonstrated lower relative expression of the above DNA repair genes at both mRNA and protein level (p < 0.001).

Conclusions This study indicates that variant types of DNA repair genes play an important role in modifying individual susceptibility to cervical cancer. Since cervical cancer is a multi-factorial disease, the contribution of DNA repair enzymes to the development of cervical cancer, if it exists may be concealed by HPV infection.

Disclosure of interests The authors declare that they have no competing interests.

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