TNF-α and IL-10 promoter polymorphisms, HPV infection, and cervical cancer risk

Although the implication of genetic factors in cervical cancer development remains to be elucidated, accumulative epidemiological evidence suggests that polymorphisms of cytokine genes may be involved in the etiology of cervical carcinoma. Tumor necrosis factor alpha (TNF-alpha) and interleukin-10 (IL-10) are two multifunctional cytokines implicated in inflammation, immunity, and cellular organization, and were proposed to play important roles in cancer biology. In order to determine whether IL-10 -1082 (G/A) and TNF-alpha -238 (G/A) and -308 (G/A) polymorphisms are associated with susceptibility to cervical cancer, a case-control study of 122 cancer patients and 176 healthy controls was conducted. Cervical samples were genotyped for both TNF-alpha polymorphisms by PCR-RFLP assay. SNP-1082 from IL-10 gene was genotyped using pyrosequencing technology. The association between cervical cancer risk and the studied SNPs was evaluated by logistic regression. Under univariate analysis, none of these polymorphisms appeared associated with susceptibility of cervical cancer development or HPV infection. However, individuals carrying heterozygous genotype for TNF-alpha -238 polymorphism seem to be at lower risk for cervical cancer development, with borderline significance (OR = 0.42, P = 0.069), as well as those carrying heterozygous genotypes for IL-10 and TNF-alpha -238 (OR = 0.40, P = 0.08). In conclusion, these results suggest a potential effect of TNF-alpha -238 G/A in the reduction of cervical cancer risk in Argentine women, but not TNF-alpha -308 or IL-10. Larger studies are needed to fully understand the genetic predisposition for the development of cervical cancer.