title: Matrix metalloproteinase genes are associated with breast cancer risk and survival: the Breast Cancer Health Disparities Study.
abstract: Matrix metalloproteinases (MMPs) contribute to cancer through their involvement in cancer invasion and metastasis. We evaluated genetic variation in MMP1 (9 SNPs), MMP2 (8 SNPs), MMP3 (4 SNPs), and MMP9 (3 SNPs) and breast cancer risk among Hispanic (2111 cases, 2597 controls) and non-Hispanic white (NHW) (1481 cases, 1586 controls) women in the Breast Cancer Health Disparities Study. Ancestral informative markers (n = 104) were assessed to determine Native American (NA) ancestry. MMP1 [4 single nucleotide polymorphisms (SNPs)] and MMP2 (2 SNPs) were associated with breast cancer overall. MMP1 rs996999 had strongest associations among women with the most NA ancestry (OR 1.61,95% CI 1.09,2.40) as did MMP3 rs650108 (OR 1.36, 95% CI 1.05,1.75) and MMP9 rs3787268 (OR 1.52, 95% CI 1.09,2.13). The adaptive rank truncated product (ARTP) showed a significant pathway p(artp)  value of 0.04, with a stronger association among women with the most NA ancestry (p(artp) = 0.02). Significant pathway genes using the ARTP were MMP1 for all women (p(artp) = 0.02) and MMP9 for women with the most NA ancestry (p(artp) = 0.024); MMP2 was borderline significant overall (p(artp) =0.06) and MMP1 and MMP3 were borderline significant for women with the most NA ancestry (p(artp) = 0.07 and 0.06 respectively). MMP1 and MMP2 were associated with ER+/PR+ and ER+/PR-tumors; MMP3 and MMP9 were associated with ER-/PR- tumors. The pathway was highly significant with survival (p(artp) = 0.0041) with MMP2 having the strongest gene association (p(artp) = 0.0007). Our findings suggest that genetic variation in MMP genes influence breast cancer development and survival in this genetically admixed population.
authors.affiliation: Department of Medicine, University of Utah, Salt Lake City, Utah, United States of America. marty.slattery@hsc.utah.edu
authors.forename: Martha L
authors.initials: ML
authors.lastname: Slattery
authors.forename: Esther
authors.initials: E
authors.lastname: John
authors.forename: Gabriela
authors.initials: G
authors.lastname: Torres-Mejia
authors.forename: Mariana
authors.initials: M
authors.lastname: Stern
authors.forename: Abbie
authors.initials: A
authors.lastname: Lundgreen
authors.forename: Lisa
authors.initials: L
authors.lastname: Hines
authors.forename: Anna
authors.initials: A
authors.lastname: Giuliano
authors.forename: Kathy
authors.initials: K
authors.lastname: Baumgartner
authors.forename: Jennifer
authors.initials: J
authors.lastname: Herrick
authors.forename: Roger K
authors.initials: RK
authors.lastname: Wolff
mesh_terms: D000328:Adult; D001943:Breast Neoplasms / Q000201:enzymology* / Q000235:genetics*; D005260:Female; D020022:Genetic Predisposition to Disease / Q000235:genetics; D006630:Hispanic or Latino; D006801:Humans; D020781:Matrix Metalloproteinase 1 / Q000235:genetics; D020778:Matrix Metalloproteinase 2 / Q000235:genetics; D019278:Matrix Metalloproteinase 3 / Q000235:genetics; D020780:Matrix Metalloproteinase 9 / Q000235:genetics; D020782:Matrix Metalloproteinases / Q000235:genetics*; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D012307:Risk Factors; D044465:White People
chemical_list: D020782:Matrix Metalloproteinases; D019278:Matrix Metalloproteinase 3; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9; D020781:Matrix Metalloproteinase 1