Variant haplotypes at XRCC1 and risk of oral leukoplakia in HPV non-infected samples

Mousumi Majumder1, Dipanjana Indra, Puspita Das Roy

  • 1Human Genetics Unit, Biological Sciences Division, Indian Statistical Institute, Kolkata, India.

Abstract

Insights

Human papillomavirus (HPV) infection increases oral cancer and leukoplakia risk. Specific genetic variations in XRCC1 DNA repair genes are linked to higher leukoplakia risk, particularly in those without HPV infection.

Area of Science:

  • Genetics
  • Oncology
  • Molecular Biology

Background:

  • Human papillomavirus (HPV) oncoproteins can inhibit DNA repair mechanisms, contributing to HPV-related carcinogenesis.
  • The study focuses on the role of genetic variations in the XRCC1 gene, a key DNA repair locus, in modulating cancer risk.

Purpose of the Study:

  • To investigate the association between XRCC1 gene polymorphisms and the risk of tobacco-related oral leukoplakia and cancer.
  • To determine if HPV infection status modifies the risk associated with XRCC1 polymorphisms.

Main Methods:

  • DNA from oral cancer (83), leukoplakia (91), and healthy controls (100) was analyzed.
  • Polymerase Chain Reaction-Restriction Fragment Length Polymorphism (PCR-RFLP) was used to detect HPV 16/18 infection and XRCC1 polymorphisms.

Main Results:

  • HPV infection significantly elevated the risk of leukoplakia (OR=2.8) and oral cancer (OR=5.5).
  • Individual XRCC1 genotypes did not alter disease risk, but pooled variant haplotypes increased leukoplakia risk in overall (OR=1.8) and HPV-negative (OR=2.2) individuals.
  • No significant association was found between XRCC1 haplotypes and oral cancer risk.

Conclusions:

  • The link between XRCC1 variant haplotypes and leukoplakia risk is more evident in HPV-negative individuals.
  • HPV oncoproteins may directly inhibit XRCC1 DNA repair activity, explaining the findings in HPV-infected individuals.
  • Further studies with larger sample sizes are needed to validate these findings for both leukoplakia and oral cancer.

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