TGFBR1 signaling and breast cancer

Over the past decade mutations discovered in genes such as BRCA1, BRCA2, TP53 and PTEN, have emerged as high-penetrance susceptibility genes and are clinically relevant for determination of breast cancer risk. Genetic counseling and subsequent screening for mutations and gene rearrangement has improved patient outcome through early detection and prophylactic interventions in patients with familial breast cancer syndromes. However, these high-penetrance genes only account for a small fraction of the hereditary linked breast cancers. It is currently believed that low-penetrance susceptibility alleles and/or environmental factors may play an important role in the remaining cases. TGFBR1*6A (*6A) is a common hypomorphic variant of the type I TGF-β receptor gene (TGFBR1) that has been associated with risk for several forms of cancer, in particular breast cancer. Several epidemiological studies have suggested that patients who carry the *6A allele have an increased risk of breast cancer. Furthermore, functional analysis suggests that this mutation alters TGF-β signaling and promotes tumorigenesis. Although a decade of research has provided basic information in regards to the prevalence of this mutation in several cancer types and populations the molecular underpinning of its functional effects are poorly understood. A better understanding of the molecular mechanism of TGFBR1 signaling in breast cancer may have an impact on breast cancer risk assessment and breast cancer prevention.