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Published on: March 11, 2014
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.
Background:
One of the mechanisms in human papillomavirus (HPV)-related carcinogenesis is inhibition of DNA repair by HPV oncoprotein. In this study, we investigated whether polymorphisms at XRCC1, one of the DNA repair loci, could modulate the risk of tobacco-related leukoplakia and cancer in HPV-infected individuals.
Methods:
Tissue DNA from 83 oral cancer, 91 leukoplakia and 100 healthy controls were screened for HPV 16/18 infection and polymorphisms at XRCC1 by PCR-RFLP to estimate the risk of diseases independently and jointly.
Results:
Human papillomavirus infection was significantly associated with increased risk of leukoplakia and cancer (OR = 2.8, 95% CI = 1.2-6.5 and OR = 5.5, 95% CI = 1.6-19, respectively). Independently, genotypes at three polymorphic sites on XRCC1 did not modulate the risk of diseases but pooled variant haplotypes increased the risk of leukoplakia in overall and HPV non-infected (OR = 1.8, 95% CI = 1.2-2.8; OR = 2.2, 95% CI = 1.2-4.0, respectively) samples but not that of cancer.
Conclusion:
The association between variant haplotypes at XRCC1 and risk of leukoplakia is pronounced in non-infected individuals since HPV oncoprotein could inhibit directly the DNA repair activity of XRCC1. But more samples of leukoplakia and cancer are essential to validate these results.
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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