Type II transmembrane serine protease gene variants associate with breast cancer

Kaisa Luostari; Jaana M Hartikainen; Maria Tengström; Jorma J Palvimo; Vesa Kataja; Arto Mannermaa; Veli-Matti Kosma

doi:10.1371/journal.pone.0102519

Type II transmembrane serine protease gene variants associate with breast cancer

PLoS One. 2014 Jul 16;9(7):e102519. doi: 10.1371/journal.pone.0102519. eCollection 2014.

Authors

Kaisa Luostari¹, Jaana M Hartikainen¹, Maria Tengström², Jorma J Palvimo³, Vesa Kataja², Arto Mannermaa¹, Veli-Matti Kosma¹

Affiliations

¹ 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.
² Institute of Clinical Medicine, Oncology, University of Eastern Finland, Kuopio, Finland; Cancer Center, Kuopio University Hospital, Kuopio, Finland.
³ Biocenter Kuopio and Cancer Center of Eastern Finland, University of Eastern Finland, Kuopio, Finland; Institute of Biomedicine, University of Eastern Finland, Kuopio, Finland.

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.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Breast Neoplasms / enzymology*
Electrophoretic Mobility Shift Assay
Female
Genetic Association Studies
Genotype
Humans
Odds Ratio
Polymorphism, Single Nucleotide / genetics*
Risk Assessment
Serine Endopeptidases / genetics*

Substances

Serine Endopeptidases
transmembrane serine protease 2, human

Grants and funding

The KBCP was financially supported by grants from the special Government Funding (EVO) of Kuopio University Hospital (www.psshp.fi), the Cancer Fund of Northern Savo (www.pohjois-savonsyopayhdistys.fi), the Finnish Cancer Organizations (www.cancer.fi), the Academy of Finland (www.aka.fi), and by the strategic funding of the University of Eastern Finland (www.uef.fi). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.