557P - Association of TGFB1 exon 1 +29 T/C polymorphism with reduced risk of sporadic breast cancer in older North Indian women population

Date 17 December 2016
Event ESMO Asia 2016 Congress
Session Poster lunch
Topics Geriatric Oncology
Presenter Ranjana Pal
Citation Annals of Oncology (2016) 27 (suppl_9): ix181-ix183. 10.1093/annonc/mdw602
Authors R. Pal1, R.N.K. Bamezai2
  • 1Life Sciences, Presidency University, 700073 - Kolkata/IN
  • 2Life Sciences, Jawaharlal Nehru University, 110067 - Delhi/IN

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-inflammatory activity and growth inhibition of early tumor cells and growth promoting activity in 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 controls in an association study for TGFB1 +29 T/C, TRAIL -716 C/T, TP53 codon 72, 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 and CASP3s in the DDR and apoptotic pathway were measured by RT-PCR.

Results

The study of TGFB1 +29 polymorphism indicated a significant difference in 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. Stratification of genotypic data revealed that in presence of protector genotypes of 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 of the protector genotypes a 2-fold protection was observed. Combined influence of TGFB1 and IFNG polymorphisms on breast cancer risk revealed that in presence of protector genotype of IFNG CA repeat, TGFB1 +29 risk genotype provided 2.5-fold protection. Furthermore, the comparison of TGFB1 transcript levels in tumors revealed significant difference for TGFB1 expression with different +29 genotype background. Also, TGFB1 +29 genotype influenced apoptosis that occurred through TRAIL mediated extrinsic pathway; CC with increased apoptosis compared to TT+TC in breast tumor patients greater than 45 years in age.

Conclusions

Thus, we conclude that as a potent inhibitor of cell proliferation and apoptosis, TGFB1 +29 CC genotype may be one of the factors responsible for less aggressive and slow growing tumors in older breast cancer patients.

Clinical trial indentification

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.