Association Study of Transforming Growth Factor Beta 1+29 T/C exon 1 Polymorphism in Breast Cancer Patients from North Indian Population

Background: TGFB1 cytokine is involved in normal mammary epithelial development as well as in breast tumorigenesis. It has role in both breast tumor suppression and progression. TGFB1 gene has several single nucleotide polymorphisms (SNPs) many of which modulate the activity of TGFB1. Our aim in this study was to analyze TGFB1 + 29 polymorphism in breast cancer individuals from North Indian population. Methods: TGFB1 + 29 T/C polymorphism was analyzed using Sanger sequencing in 285 breast cancer patients and age matched 363 healthy controls from North Indian population. Next, transcript expression of 13 apoptotic genes, TRAIL, DR4, DR5, DcR1, DcR2, Bcl2, cytochrome c, Casp8L, Casp8, FlipS, FlipL, Casp3s and Casp3 were carried out in 77 breast tumor tissues obtained from 77 individuals. Results: TGFB1 + 29 CC genotype provided protection against the development of breast cancer (P = 0.012). This was mainly attributable to higher age group (> 45 years) women (P = 0.016). Individuals having CC protector genotype showed significantly higher expression of TGFB1 transcript compared to the TT and TC risk genotypes (P = 0.044). Furthermore, we observed that TGFB1 + 29 CC genotype showed increased TRAIL mediated apoptosis via the extrinsic pathway in breast tumor patients with age greater than 45 years (P = 0.027). Conclusion: TGFB1 + 29 homozygous mutant CC genotype is related to protection against breast cancer in North Indian women population greater than 45 years of age.