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Northwestern’s cancer genetics program ID’s gene variant that increases colon cancer risk


A paper published in this week’s Journal of Clinical Oncology says Transforming Growth Factor Beta Receptor 1*6A (TGFBR1*6A) – a mutated gene present in nearly one in eight people and the most commonly inherited cancer susceptibility gene identified so far – might be responsible for a significant proportion of familial colorectal cancers. The study, published by researchers at Northwestern Memorial Hospital and Northwestern University’s Robert H. Lurie Comprehensive Cancer Center, says 15 to 20 percent of all colorectal cancers are familial, but only 7-8 percent are caused by mutations of known colorectal cancer genes such as the APC, MLH1, MSH2 and MSH6 genes.

In an earlier study, Dr. Pasche and his colleagues had found that TGFBR1*6A may increase the risk for all colon cancers by 20 percent. "There is growing evidence that TGFBR1*6A is associated with an increased risk of colorectal cancer but its specific contribution to familial colorectal cancer was unknown," explained Dr. Pasche. Now, Dr. Pasche believes the gene is especially potent as a cause for familial colon cancers.

The study looked at 208 patients with colorectal cancer and a strong family history of colorectal cancer and found that the number of TGFBR1*6A carriers was twice as high among patients without a mutation in the colorectal cancer genes MLH1, MSH2 and MSH6 as compared with patients without a mutation in these genes. The number of carriers of two copies of the TGFBR1*6A gene was 13-fold higher than in the general population, suggesting that TGFBR1*6A homozygosity (possessing two identical forms of a particular gene, one inherited from each parent) is associated with a particularly high risk of colorectal cancer.

Colorectal cancers are the second leading cause of cancer death among adult Americans and familial colorectal cancer is a major public health problem because it causes a relatively large percentage of these cancers. "We wanted to identify the genes responsible for the remaining unexplained familial colorectal cancers," says Dr. Pasche. "That is a first step toward better prevention and treatment of those cancers."

Altered genes trigger all cancer. "Most cases of breast, ovarian and colon cancers are caused by damage to the genes that builds up over a lifetime, but some people are born with a high risk of the disease," explains Pasche. "When inherited, the TGFRB1*6A gene makes people susceptible to having certain cells grow and divide uncontrollably, which may contribute to cancer development."

Amanda Widtfeldt | EurekAlert!
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