BACKGROUND: Investigation of the potential association of single nucleotide polymorphisms (SNPs) at -308 G/A and -238 G/A of Tumor necrosis factor alpha (TNFalpha) 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 TNFalpha 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 TNFalpha 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 TNFalpha-238 (G/A) polymorphism with the risk of development of cervical cancer. CONCLUSION: It suggests that SNP at -308 (G/A) of TNFalpha promoter may represent an increased risk for HPV infection and development of cervical cancer in Indian women.
BACKGROUND: Investigation of the potential association of single nucleotide polymorphisms (SNPs) at -308 G/A and -238 G/A of Tumor necrosis factor alpha (TNFalpha) with susceptibility to HPV-16 associated cervical cancer in Indian women. METHODS: The study included 165 histologically confirmed cases with 45 precancer and 120 cancerpatients and an equal number (165) of healthy controls with normal cervical cytology. PCR-RFLP was employed to analyze TNFalpha 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 TNFalpha 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 16infection 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 TNFalpha-238 (G/A) polymorphism with the risk of development of cervical cancer. CONCLUSION: It suggests that SNP at -308 (G/A) of TNFalpha promoter may represent an increased risk for HPV infection and development of cervical cancer in Indian women.
Authors: Adam D Kenney; James A Dowdle; Leonia Bozzacco; Temet M McMichael; Corine St Gelais; Amanda R Panfil; Yan Sun; Larry S Schlesinger; Matthew Z Anderson; Patrick L Green; Carolina B López; Brad R Rosenberg; Li Wu; Jacob S Yount Journal: Annu Rev Genet Date: 2017-08-30 Impact factor: 16.830