TNFα–308G/A Polymorphism as a Risk Factor for HPV Associated Cervical Cancer in Indian Population

Indu Kohaar,Veena Singh,B C Das,Pushpa Sodhani,Sudha Salhan,Anita Sharma,Mausumi Bharadwaj,Debi P Sarkar,Swaraj Batra,Nisha Thakur

doi:10.1155/2007/418247

Abstract

Background: Investigation of the potential association of single nucleotide polymorphisms (SNPs) at –308 G/A and –238 G/A of Tumor necrosis factor α (TNFα) with susceptibility to HPV-16 associated cervical cancer in Indian women. Methods: The study included 165 histologically confirmed cases with 45 precancer and 120 cancer patients and an equal number (165) of healthy controls with normal cervical cytology. PCR-RFLP was employed to analyze TNFα promoter polymorphisms, which were confirmed by direct sequencing. Both patients and controls were screened for Human Papillomavirus (HPV) infection. Results: The frequency of –308 A allele in TNFα was significantly higher in cases compared with control subjects (21% in cases vs. 9% in controls; p < 0.01), with an odds ratio of 2.7 (95% CI = 1.41–5.15). Also, women carrying A allele for this locus presented 3 times increased susceptibility to HPV 16 infection as evident from carrier genotype distribution between HPV positive cases and control subjects (24% in HPV positive cases vs. 9% in controls; p < 0.01; OR = 3.1; 95% CI = 1.60–6.03). No such association was found for TNFα–238 (G/A) polymorphism with the risk of development of cervical cancer. Conclusion: It suggests that SNP at –308 (G/A) of TNFα promoter may represent an increased risk for HPV infection and development of cervical cancer in Indian women.

Highlights

Cancer of the uterine cervix is the second most common cancer among women worldwide but it is the most common cancer in Indian women [6]
The age and ethnicity matched control group consisting of 165 healthy women with no self or family history of any neoplastic disease and with normal cervical cytology were from outdoor patients of Department of Gynaecology, Safdarjung hospital, New Delhi, who came for routine checkup
The estimated odds ratio of carrier genotype (GA/AA) to GG genotype was 2.7, which indicated an increased risk for the development of the cervical cancer in women carrying A allele

Summary

Introduction

Cancer of the uterine cervix is the second most common cancer among women worldwide but it is the most common cancer in Indian women [6]. PCR-RFLP was employed to analyze TNFα promoter polymorphisms, which were confirmed by direct sequencing Both patients and controls were screened for Human Papillomavirus (HPV) infection. Women carrying A allele for this locus presented 3 times increased susceptibility to HPV 16 infection as evident from carrier genotype distribution between HPV positive cases and control subjects (24% in HPV positive cases vs 9% in controls; p < 0.01; OR = 3.1; 95% CI = 1.60–6.03). No such association was found for TNFα–238 (G/A) polymorphism with the risk of development of cervical cancer. Conclusion: It suggests that SNP at –308 (G/A) of TNFα promoter may represent an increased risk for HPV infection and development of cervical cancer in Indian women

Methods

Results

Conclusion