557P Association of TGFB1 exon 1 129 T/C polymorphism with reduced risk of sporadic breast cancer in older North Indian women population

Abstract

Background Transforming growth factor beta 1 (TGFB1) is a cytokine secreted by immune cells that plays an important role in breast tumorigenesis. It shows dual characteristics:anti-inflammatoryactivityandgrowthinhibitionofearlytumor cells and growth promoting activityin advanced tumor. Here, we investigated the association between TGFB1 +29 polymorphism and breast cancer risk in North Indian population. Methods We analyzed 285 patients with sporadic breast tumor and 363 healthy controlsinanassociationstudyforTGFB1+29T/C,TRAIL-716C/T,TP53codon72, IFNG CA repeat polymorphism using DNA sequencing or SSLP. The expression levels of TGFB1,TRAIL,DR4,DR5,DCR1,DCR2,CYCS,BCL2,CASP8,CASP8L,FLIPL, FLIPS,CASP3 andCASP3sintheDDRandapoptoticpathwayweremeasuredbyRT- PCR. Results The study of TGFB1 +29polymorphismindicatedasignificantdifferencein the genotype distribution between patients and controls. The predominant TT and TC genotypes, when compared against CC genotype, provided 1.7-fold risk. This association was mainly attributable to higher age group (> 45 years) women. Stratificationofgenotypicdatarevealedthatinpresenceofprotectorgenotypesof TGFB1 +29 CC and TRAIL -716 CT and TT genotypes, a 2.5-fold protection was observed. Studies carried out on TGFB1 +29 and TP53 codon 72 interaction showed that in presence ofthe protector genotypes a 2-fold protection was observed. Combined influence of TGFB1 and IFNG polymorphisms on breast cancer risk revealed that in presenceofprotectorgenotypeofIFNGCArepeat,TGFB1 +29riskgenotypeprovided 2.5-foldprotection.Furthermore,thecomparisonofTGFB1 transcriptlevelsintumors revealed significant difference for TGFB1 expression with different +29 genotype background.Also,TGFB1 +29genotypeinfluencedapoptosisthatoccurredthrough TRAIL mediated extrinsic pathway; CC with increased apoptosis compared to TT+TC in breast tumor patients greater than 45 years in age. Conclusions:Thus,weconcludethatasapotentinhibitorofcellproliferationand apoptosis,TGFB1 +29CCgenotypemaybeoneofthefactorsresponsibleforless aggressive and slow growing tumors in Legal entity responsible for the study: Jawaharlal Nehru University, New Delhi, India Funding Council of Scientific and Industrial Research, University Grants Commission, Department of Biotechnology Disclosure All authors have declared no conflicts of interest.