Role of ethnic variations in TNF-alfa and TNF-bita polymorphisms and risk of breast cancer in India

Abstract

TNF-alfa and -bita are multi-functional pro-inflammatory cytokines known to play important roles in both tumor progression and destruction based on their concentrations. Growth factors and various stimuli such as cytokines regulate proliferation of the breast epithelial cells. Therefore, the polymorphisms in the genes encoding these signaling molecules could affect the risk of breast cancer. We have investigated selected genetic polymorphisms in TNF-alfa promoter (rs1800629, -308 G>A and rs361525, -238 G>A) and TNF-bita intron 1 (rs909253, +252 A>G) in ethnically two different case-control groups from India. The study included 200 cases and 200 controls from Indo-European (North Indian) group, and 265 cases and 237 controls from a Dravidian (South Indian) group. Genotyping of a total of 902 individuals was done by direct DNA sequencing. None of the polymorphisms showed significant association with breast cancer in the Indo-European group; however, all the three polymorphisms showed strong association with breast cancer in the Dravidian group. Further, sub-group analysis in Indo-European group showed no significant difference between pre-menopausal cases and controls or between post-menopausal cases and controls at any of the loci analyzed. However, all the polymorphisms in Dravidian group were significantly associated with pre-menopausal but not with post-menopausal breast cancer. In conclusion, TNF-alfa and -bita polymorphisms are strongly associated with breast cancer in Dravidian but not in Indo-European group.