Study of Association of TGF-ß1 Polymorphism with Breast Density in a Tertiary Medical Center of Malaysia

Early detection of breast cancer  risk by screening  tools such as mammography can reduces  the cost of treatment  management and the prognosis  of the disease.  The level of breast density of in mammogram is one of the potential  cofounder factor for breast cancer  risk. The development of mammary  epithelial  cells is determined by the  genetic  factor.  Transforming  growth  factor-beta  (TGF-ß) gene  involves  in the regulation  of cell proliferation and cell division. This study aimed to assess the association of TGF-ß1 polymorphisms with  breast  density  among  women  who underwent breast  screening  using mammogram. The detection of genotypes  for three polymorphisms of TGF-ß1 assigned as rs1800469, rs1800470 and rs4803455 were performed using PCR-RFLP technique. The allele and genotype  frequencies were calculated for control  group that consists of BIRADS 1 and BIRADS 2 class whilst case group consisted of BIRADS 3 and BIRADS 4 class. Two polymorphisms (rs1800469 and  rs1800470) yielded  a significant association with breast  density with p value of 0.004  and 0.003,  respectively.  However, the third polymorphism, rs4803455 did  not  yield  a  significant  association (p  value=0.090).  Haplotype association analysis might suggest the haplotype GAA conferred susceptibility  (p value= 0.02, OR=2.21[1.07-4.55]) rather thanhaplotypeAAC predispose aprotective effect (p value=0.004, OR=0.40[0.21-0.77]) to breast  density  development. This preliminary  data on single and haplotype association might reveal the association of polymorphisms of TGF-ß1 with breast density and give an insight on the role of polymorphism in predisposing to breast density development.