Associations of Polymorphic Loci of Matrix Metalloproteinase Genes with Breast Cancer in Women of the Central Black Earth Region of Russia

Polymorphic variants of matrix metalloproteinase (MMP) genes were tested for association with breast cancer (BC) in women of the Central Black Earth Region (CBER) of Russia with consideration to whether a patient has or does not have a family history of BC. The study included 358 BC patients (of which 68 had a family history of BC) and 746 control women. Genotyping was performed at ten polymorphic MMP loci: rs1799750 of MMP1; rs243865 of MMP2; rs679620 of MMP3; rs1940475 of MMP8; and rs17576, rs17577, rs3918242, rs2250889, rs3787268, and rs3918249 of MMP9. Logistic regression was performed to assess the associations of the MMP variants with BC in the patient subgroups with or without a family history of BC (the control group was the same for the two subgroups). Low risk of BC in women with a family history of BC was associated with MMP2 rs243865 (OR 0.53-0.54, p(perm) & LE; 0.03) and MMP9 rs2250889 (OR 0.36-0.37, p(perm) & LE; 0.04). Higher risk of BC in women without a family history of BC was associated with MMP9 rs3787268 (OR = 2.16, p(perm) = 0.03) and the following haplotypes at the MMP9 polymorphisms (p(perm) & LE; 0.05): CA at rs3918249-rs17576 (OR = 2.15), CCA at rs3918242-rs3918249-rs17576 (OR = 1.69), CCAG at rs3918242-rs3918249-rs17576-rs3787268 (OR = 1.69), and CAGCG at rs3918249-rs17576-rs3787268-rs2250889-rs17577 (OR = 3.06). Three haplotypes were associated with a low risk of BC in women without a family history of BC: GG at rs17576-rs3787268 (OR = 0.60), GGC at rs17576-rs3787268-rs2250889 (OR = 0.63), and CGG at rs3918249-rs17576-rs3787268 (OR = 0.62).