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

Type II transmembrane serine protease gene variants associate with breast cancer

Kaisa Luostari  1 , Jaana M Hartikainen  1 , Maria Tengström  2 , Jorma J Palvimo  3 , Vesa Kataja  2 , Arto Mannermaa  1 , Veli-Matti Kosma  1
Affiliations

Type II transmembrane serine protease gene variants associate with breast cancer

Kaisa Luostari et al. PLoS One. .

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.

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Conflict of interest statement

Competing Interests: Arto Mannermaa is a PLOS ONE Editorial Board member. This does not alter the authors’ adherence to PLOS ONE Editorial policies and criteria.

Figures

Figure 1
Figure 1. BCSS in multivariate analysis (Cox regression).
A, rs12151195; B, rs12461158; C, rs2276205; D, rs3814903; E, rs2399403 genotypes; and F, combined risk allele variable. Age, tumor grade, histological type, tumor size, nodal status, ER status, and HER2 status were included in the multivariate analysis. P≤0.05 was considered significant.
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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.