title: Type II transmembrane serine protease gene variants associate with breast cancer.
abstract: Type II transmembrane serine proteases (TTSPs) are related to tumor growth, invasion, and metastasis in cancer. Genetic variants in these genes may alter their function, leading to cancer onset and progression, and affect patient outcome. Here, 464 breast cancer cases and 370 controls were genotyped for 82 single-nucleotide polymorphisms covering eight genes. Association of the genotypes was estimated against breast cancer risk, breast cancer-specific survival, and survival in different treatment groups, and clinicopathological variables. SNPs in TMPRSS3 (rs3814903 and rs11203200), TMPRSS7 (rs1844925), and HGF (rs5745752) associated significantly with breast cancer risk (Ptrend = 0.008-0.042). SNPs in TMPRSS1 (rs12151195 and rs12461158), TMPRSS2 (rs2276205), TMPRSS3 (rs3814903), and TMPRSS7 (rs2399403) associated with prognosis (P = 0.004-0.046). When estimating the combined effect of the variants, the risk of breast cancer was higher with 4-5 alleles present compared to 0-2 alleles (P = 0.0001; OR, 2.34; 95% CI, 1.39-3.94). Women with 6-8 survival-associating alleles had a 3.3 times higher risk of dying of breast cancer compared to women with 1-3 alleles (P = 0.001; HR, 3.30; 95% CI, 1.58-6.88). The results demonstrate the combined effect of variants in TTSPs and their related genes in breast cancer risk and patient outcome. Functional analysis of these variants will lead to further understanding of this gene family, which may improve individualized risk estimation and development of new strategies for treatment of breast cancer.
authors.affiliation: Institute of Clinical Medicine, Pathology and Forensic Medicine, University of Eastern Finland, Kuopio, Finland; Biocenter Kuopio and Cancer Center of Eastern Finland, University of Eastern Finland, Kuopio, Finland; Imaging Center, Clinical Pathology, Kuopio University Hospital, Kuopio, Finland.
authors.forename: Kaisa
authors.initials: K
authors.lastname: Luostari
authors.affiliation: Institute of Clinical Medicine, Pathology and Forensic Medicine, University of Eastern Finland, Kuopio, Finland; Biocenter Kuopio and Cancer Center of Eastern Finland, University of Eastern Finland, Kuopio, Finland; Imaging Center, Clinical Pathology, Kuopio University Hospital, Kuopio, Finland.
authors.forename: Jaana M
authors.initials: JM
authors.lastname: Hartikainen
authors.affiliation: Institute of Clinical Medicine, Oncology, University of Eastern Finland, Kuopio, Finland; Cancer Center, Kuopio University Hospital, Kuopio, Finland.
authors.forename: Maria
authors.initials: M
authors.lastname: Tengström
authors.affiliation: Biocenter Kuopio and Cancer Center of Eastern Finland, University of Eastern Finland, Kuopio, Finland; Institute of Biomedicine, University of Eastern Finland, Kuopio, Finland.
authors.forename: Jorma J
authors.initials: JJ
authors.lastname: Palvimo
authors.affiliation: Institute of Clinical Medicine, Oncology, University of Eastern Finland, Kuopio, Finland; Cancer Center, Kuopio University Hospital, Kuopio, Finland.
authors.forename: Vesa
authors.initials: V
authors.lastname: Kataja
authors.affiliation: Institute of Clinical Medicine, Pathology and Forensic Medicine, University of Eastern Finland, Kuopio, Finland; Biocenter Kuopio and Cancer Center of Eastern Finland, University of Eastern Finland, Kuopio, Finland; Imaging Center, Clinical Pathology, Kuopio University Hospital, Kuopio, Finland.
authors.forename: Arto
authors.initials: A
authors.lastname: Mannermaa
authors.affiliation: Institute of Clinical Medicine, Pathology and Forensic Medicine, University of Eastern Finland, Kuopio, Finland; Biocenter Kuopio and Cancer Center of Eastern Finland, University of Eastern Finland, Kuopio, Finland; Imaging Center, Clinical Pathology, Kuopio University Hospital, Kuopio, Finland.
authors.forename: Veli-Matti
authors.initials: VM
authors.lastname: Kosma
mesh_terms: D001943:Breast Neoplasms / Q000201:enzymology*; D024202:Electrophoretic Mobility Shift Assay; D005260:Female; D056726:Genetic Association Studies; D005838:Genotype; D006801:Humans; D016017:Odds Ratio; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D018570:Risk Assessment; D012697:Serine Endopeptidases / Q000235:genetics*
chemical_list: D012697:Serine Endopeptidases; C421305:TMPRSS2 protein, human