Matriptase‐2 gene (TMPRSS6) variants associate with breast cancer survival, and reduced expression is related to triple‐negative breast cancer. Issue 10 (4th June 2013)

• Record Type: Journal Article
• Authors: Tuhkanen, Hanna; Hartikainen, Jaana M.; Soini, Ylermi; Velasco, Gloria; Sironen, Reijo; Nykopp, Timo K.; Kataja, Vesa; Eskelinen, Matti; Kosma, Veli‐Matti; Mannermaa, Arto
• Is Part Of: International journal of cancer. Volume 133:Issue 10(2013:Nov. 15)
• Page Start: 2334
• Page End: 2340
• Publication Date: 2013-06-04
• Subjects: Cancer -- Periodicals; Cancer -- Prevention -- Periodicals; 616.994
• DOI: 10.1002/ijc.28254
• Languages: English
• ISSNs: 0020-7136

Abstract

<abstract abstract-type="main"> <title> <x xml:space="preserve">Abstract</x> </title> <p>Matriptase‐2 (<italic>TMPRSS6</italic>) has been identified as a breast cancer risk factor. Here, we examined relationships between <italic>TMPRSS6</italic> genetic variations and breast cancer risk and survival, and determined the gene and protein expressions in breast tumors and assessed their clinical importance. Thirteen <italic>TMPRSS6</italic> 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 <italic>TMPRSS6</italic> variant rs2543519 was associated with breast cancer risk (<italic>p</italic> = 0.032). Multivariate analysis showed that four variants had effects on survival—rs2543519 (<italic>p</italic> = 0.017), rs2235324 (<italic>p</italic> = 0.038), rs14213212 (<italic>p</italic> = 0.044) and rs733655 (<italic>p</italic> = 0.021)—which were used to create a group variable that was associated with poorer prognosis correlating with more alleles related to reduced survival (<italic>p</italic> = 0.006; risk ratio, 2.375; 95% confidence interval, 1.287–4.382). Low gene expression was related to triple‐negative breast cancer (<italic>p</italic> = 0.0001), and lower protein expression was detected in undifferentiated (<italic>p</italic> = 0.019), large (<italic>p</italic> = 0.014) and ductal or lobular tumors (<italic>p</italic> = 0.036). These results confirm the association of <italic>TMRRSS6</italic> 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.</p> </abstract>