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

Abstract

The association of polymorphic variants of matrix metalloproteinase (MMP) genes with breast cancer (BC) in women of the Central Chernozem region of Russia, taking into account the presence/absence of a burdened family history, was studied. The study included 358 patients with breast cancer (68 patients had a burdened family history) and 746 women of the control group. Genotyping of 10 polymorphic loci of MMP genes (rs1799750 MMP1; rs243865 MMP2; rs679620 MMP3; rs1940475 MMP8; rs17576, rs17577, rs3918242, rs2250889, rs3787268, rs3918249 MMP9) was performed. To study the associations of polymorphic variants of MMP genes with breast cancer in two subgroups, taking into account the presence/absence of a burdened family history (the control group for these two subgroups was the same), the method of logistic regression analysis was used. It was revealed that a low risk of developing the disease among women with a burdened family history is associated with polymorphisms rs243865 MMP2 (OR = 0.53–0.54, pperm ≤ 0.03) and rs2250889 MMP9 (OR = 0.36–0.37, pperm ≤ 0.04). In women without burdened heredity, an increased risk of developing breast cancer is associated with rs3787268 MMP9 (OR = 2.16, pperm = 0.03) and haplotypes of polymorphic loci of the MMP9 gene (pperm ≤ 0.05): CA rs3918249–rs17576 (OR = 2.15), CCA rs3918242–rs3918249–rs17576 (OR = 1.69), CCAG rs3918242–rs3918249–rs17576–rs3787268 (OR = 1.69), CAGCG rs3918249–rs17576–rs3787268–rs2250889–rs17577 (OR = 3.06). Three haplotypes are associated with a low risk of breast cancer in women without burdened heredity: GG rs17576–rs3787268 (OR = 0.60), GGC rs17576–rs3787268–rs2250889 (OR = 0.63), and CGG rs3918249–rs17576–rs3787268 (OR = 0.62).