TGFBR1*6A as a modifier of breast cancer risk and progression: advances and future prospects.

Abstract

There is growing evidence that germline mutations in certain genes influence cancer susceptibility, tumor evolution, as well as clinical outcomes. Identification of a disease-causing genetic variant enables testing and diagnosis of at-risk individuals. For breast cancer, several genes such as BRCA1, BRCA2, PALB2, ATM, and CHEK2 act as high- to moderate-penetrance cancer susceptibility genes. Genotyping of these genes informs genetic risk assessment and counseling, as well as treatment and management decisions in the case of high-penetrance genes. TGFBR1*6A (rs11466445) is a common variant of the TGF-β receptor type I (TGFBR1) that has a global minor allelic frequency (MAF) of 0.051 according to the 1000 Genomes Project Consortium. It is emerging as a high frequency, low penetrance tumor susceptibility allele associated with increased cancer risk among several cancer types. The TGFBR1*6A allele has been associated with increased breast cancer risk in women, OR 1.15 (95% CI 1.01-1.31). Functionally, TGFBR1*6A promotes breast cancer cell proliferation, migration, and invasion through the regulation of the ERK pathway and Rho-GTP activation. This review discusses current findings on the genetic, functional, and mechanistic associations between TGFBR1*6A and breast cancer risk and proposes future directions as it relates to genetic association studies and mechanisms of action for tumor growth, metastasis, and immune suppression.

• Authors: Kojo Agyemang, Allan M Johansen, Grayson W Barker, Michael J Pennison, Kimberly Sheffield, Hugo Jimenez, Carl Blackman, Sambad Sharma, Patrick A Fordjour, Ravi Singh, Katherine L Cook, Hui-Kuan Lin, Wei Zhang, Hui-Wen Lo, Kounosuke Watabe, Peiqing Sun, Carl D Langefeld, Boris Pasche
• Journal: NPJ breast cancer (NPJ Breast Cancer) Vol. 8 Issue 1 Pg. 84 (Jul 19 2022) ISSN: 2374-4677 [Print] United States
• PMID: 35853889 (Publication Type: Journal Article, Review)
• Copyright: © 2022. The Author(s).