title: Matriptase-2 gene (TMPRSS6) variants associate with breast cancer survival, and reduced expression is related to triple-negative breast cancer.
abstract: Matriptase-2 (TMPRSS6) has been identified as a breast cancer risk factor. Here, we examined relationships between TMPRSS6 genetic variations and breast cancer risk and survival, and determined the gene and protein expressions in breast tumors and assessed their clinical importance. Thirteen TMPRSS6 polymorphisms were genotyped in 462 invasive breast cancer cases and 458 controls. Gene expression was analyzed from 83 tumors and protein expression from 370 tumors. We then assessed the statistical significance of associations among genotypes, clinicopathological characteristics and survival. The TMPRSS6 variant rs2543519 was associated with breast cancer risk (p = 0.032). Multivariate analysis showed that four variants had effects on survival-rs2543519 (p = 0.017), rs2235324 (p = 0.038), rs14213212 (p = 0.044) and rs733655 (p = 0.021)-which were used to create a group variable that was associated with poorer prognosis correlating with more alleles related to reduced survival (p = 0.006; risk ratio, 2.375; 95% confidence interval, 1.287-4.382). Low gene expression was related to triple-negative breast cancer (p = 0.0001), and lower protein expression was detected in undifferentiated (p = 0.019), large (p = 0.014) and ductal or lobular tumors (p = 0.036). These results confirm the association of TMRRSS6 variants with breast cancer risk and survival. Matriptase-2 levels decrease with tumor progression, and lower gene expression is seen in poor-prognosis-related triple-negative breast cancers. Our study is the first to show that matriptase-2 gene variants are related to breast cancer prognosis, supporting matriptase-2 involvement in tumor development.
authors: Institute of Clinical Medicine, Pathology and Forensic Medicine, University of Eastern Finland, Kuopio, Finland; Biocenter Kuopio and Cancer Center of Easter Finland, University of Eastern Finland, Kuopio, Finland; Imaging Center, Clinical Pathology, Kuopio University Hospital, Kuopio, Finland.
authors: Hanna
authors: H
authors: Tuhkanen
authors: Jaana M
authors: JM
authors: Hartikainen
authors: Ylermi
authors: Y
authors: Soini
authors: Gloria
authors: G
authors: Velasco
authors: Reijo
authors: R
authors: Sironen
authors: Timo K
authors: TK
authors: Nykopp
authors: Vesa
authors: V
authors: Kataja
authors: Matti
authors: M
authors: Eskelinen
authors: Veli-Matti
authors: VM
authors: Kosma
authors: Arto
authors: A
authors: Mannermaa
mesh_terms: D000483:Alleles; D001943:Breast Neoplasms / Q000201:enzymology* / Q000235:genetics*; D018450:Disease Progression; D005260:Female; D015870:Gene Expression / Q000235:genetics; D005838:Genotype; D006801:Humans; D008565:Membrane Proteins / Q000235:genetics*; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D011379:Prognosis; D012306:Risk; D012697:Serine Endopeptidases / Q000235:genetics*; D015996:Survival Rate; D064726:Triple Negative Breast Neoplasms / Q000201:enzymology* / Q000235:genetics*
chemical_list: D008565:Membrane Proteins; D012697:Serine Endopeptidases; C504318:TMPRSS6 protein, human
keywords: breast cancer; expression; genetic variation; matriptase-2; survival