Article type: Research Article
Authors: Kohaar, Indu | Thakur, Nisha | Salhan, Sudha | Batra, Swaraj | Singh, Veena | Sharma, Anita | Sodhani, Pushpa | Das, B.C. | Sarkar, Debi P. | Bharadwaj, Mausumi;
Affiliations: Division of Molecular Genetics & Biochemistry, Institute of Cytology & Preventive Oncology (ICMR), I-7, Sector 39, Noida, India | Department of Obstetrics and Gynaecology, Safdarjung Hospital, New Delhi, India | Department of Obstetrics & Gynaecology, LNJP Hospital, New Delhi, India | Division of Clinical Oncology, Institute of Cytology & Preventive Oncology (ICMR), I-7, Sector 39, Noida, India | Division of Cytopathology, Institute of Cytology & Preventive Oncology (ICMR), I-7, Sector 39, Noida, India | Division of Molecular Oncology, Institute of Cytology & Preventive Oncology (ICMR), I-7, Sector 39, Noida, India | Department of Biochemistry, University of Delhi (South Campus), New Delhi, India
Note: [] Corresponding author: Mausumi Bharadwaj, Division of Molecular Genetics & Biochemistry, Institute of Cytology & Preventive Oncology (ICMR), I-7, Sector 39, Noida 201301, India. Tel.: +91 95120 2579471; Fax: +91 95120 2579473; E-mail: mausumi02@yahoo.com, bharadwajm@icmr.org.in.
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.
Keywords: Tumor necrosis factor α (TNFα), single nucleotide polymorphism, –308 promoter polymorphism, –238 promoter polymorphism, cervical precancer, cervical cancer, human papillomavirus, genetic susceptibility
Journal: Analytical Cellular Pathology, vol. 29, no. 3, pp. 249-256, 2007
