Decreased activity within the Transforming Growth Factor Beta (TGF-beta) pathway is associated with increased breast cancer risk, according to a study published by researchers at Northwestern Memorial Hospital and Northwestern University’s Robert H. Lurie Comprehensive Cancer Center in today’s Cancer Research journal. This is the first study aimed at determining whether various combinations of two naturally-occurring variants of the TGF-beta pathway may predict breast cancer risk. It is also the first study assessing a cancer-related pathway by means of two functionally-relevant variants.
Blood tests were performed on 660 patients with breast cancer and 880 healthy females for two TGF-beta variants: TGFBR1*6A and TGFB1 T29C. "Our study shows that TGFBR1*6A is associated with a 120 percent increased risk of breast cancer among women older than 50," says study author Boris Pasche, MD, PhD, FACP, director of Northwestern’s Cancer Genetics Program and assistant professor of Medicine at Northwestern University’s Feinberg School of Medicine. "Importantly, the results show that women with the lowest levels of TGF-beta activity have a 69 percent higher risk of breast cancer than women with the highest levels of TGF-beta activity as predicted by the combination of the two variants TGFBR1*6A and TGFB1 T29C. This finding is promising as it may eventually help us predict breast cancer risk in a large subset of the population. Indeed, breast cancer risk may be predicted in 30 percent of women through assessment of the TGFBR1*6A and TGFB1 T29C variants."
Mutated genes like TGFBR1*6A and the better-known cancer susceptibility genes BRCA1 and BRCA2, alter cells in a way that causes them either to grow faster or become cancerous. Dr. Pasche says while BRCA1 and BRCA2 genes have been implicated in an estimated 3 to 7 percent of all breast and ovarian cancer cases, studying TGFBR1*6A is important because it is a far more common gene as one in every eight individual carries at least one copy of this gene. The BRCA1 and BRCA2 genes are found only in one of every 400 to 800 people. The impact of TGFBR1*6A is shown by the fact that in 2005 more than 14,000 new cases of breast cancers in the US alone may be attributable to TGFBR1*6A.
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