Role of ethnic variations in TNF-α and TNF-β polymorphisms and risk of breast cancer in India

Abstract

TNF-α and -β, the multi-functional pro-inflammatory cytokines, are 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-α promoter (rs1800629, -308 G>A and rs361525, -238 G>A) and TNF-β intron 1 (rs909253, +252 A>G) in ethnically two different case-control groups from India. The study included 200 cases and 200 controls from an 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 the 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 the Dravidian group were significantly associated with pre-menopausal but not with post-menopausal breast cancer. In conclusion, TNF-α and -β polymorphisms are strongly associated with breast cancer in the Dravidian but not in the Indo-European group.

Association of the tumor necrosis factor-alpha -308G>A polymorphism with breast cancer in Mexican women

“…In our population, the frequency of this polymorphism was 14% in BC patients and 1% in controls and was identified as a risk factor. Other studies have observed the association between the -308G>A polymorphism and BC (Li et al, 2008;Pooja et al, 2011;Shen et al, 2011).…”

Association of TNF-α-308 and -238 Polymorphisms with Risk of Cervical Cancer: A Meta-analysis

“…Accordingly, it is rational to speculate that TNF-α -308G>A and -238G>A polymorphisms may have an impact on the development of some types of cancers. In recent years, numerous casecontrol studies have been conducted to investigate the associations of TNF-α -308G>A and -238G>A promoter region polymorphisms with cancer risk, suggesting that these polymorphisms may be associated with cancer susceptibility, such as breast cancer, lung cancer, nasopharyngeal cancer and cervical cancer (Deshpande et al, 2005;Shih et al, 2006;Pooja et al, 2011;Sousa et al, 2011).…”

An Analysis of Polymorphism Lymphotoxin alpha +252 A>G in South Indian Breast Cancer Patients

“…16,19 Similarly, in two North India studies, polymorphism was significantly associated with breast cancer susceptibility with OR of 1.43 and 2.38. 20,21 Our study, comprising more of south India women may show ethnic variation. The lack of significant association of rs 909253 SNP is consistent with the previous studies from the US and Iran.…”