Biomedicine

Abstract

Introduction and Aim: Breast density has been used as a potential cofounder factor in breast carcinoma risk. The breast density is determined by several genes that involved in cell proliferation, particularly Transforming Growth Factor-Beta 1 (TGF-ß1). A defect in TGF-ß1 molecular pathway may lead to abnormal cell proliferation which is seen in human cancers, particularly breast carcinoma. This preliminary study was aimed to predict the predisposing haplotypes of TGF- ß1 among Malay women in Kuala Terengganu with breast density. Materials and Methods: The participants were recruited among women who underwent mammography check-up at Department of Radiography, Hospital Sultanah Nur Zahirah of Kuala Terengganu. The case group (n=44) was consisted of individuals with BIRADS 1 and BIRADS 2, while the control group (n=48) was taken among individuals with BIRADS 3 and BIRADS 4. SNP genotyping was conducted for three main TGF-ß1 variants, assigned as rs1800469, rs1800470 and rs4803455 using PCR-RFLP technique. Results:Two SNPs (rs1800469 and rs180047) did reveal a significant association with breast density with a p value of 0.008 and 0.006, respectively. However, rs4803455 did not yield association in this small cohort. In a further investigation, haplotype GAA conferred a susceptible haplotype (p value=0.027, OR=2.28 [1.09- 4.76]) towards breast density whilst haplotype AAC projected a significant association with protective effect (p value=0.018, OR=0.45[0.23-0.88]) in breast density development. Conclusion:This pilot study might provide baseline information on the role of TGF-ß1 haplotypes in determining the density of breast that projected a genetic determinant as a risk factor for breast carcinoma among Malay women.