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Michigan Researchers Identify Novel MLH1 Mutation Linked to Colorectal Cancer

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A team of researchers from Michigan and the University of California-Irvine claims to have identified a “virulent new” genetic risk factor for colorectal cancer. These findings, if verified, may help oncologists to better select patients for certain treatment options.

Steven Lipkin, director of the cancer genetics clinic at UC Irvine’s Chao Family Comprehensive Cancer Center and Stephen Gruber, of the University of Michigan, found what they called a “novel mutant gene” in a population of Israeli colorectal cancer patients. They said this mutation, a variant of MLH1, can “significantly” increase the risk of developing the disease. These results were published online June 6 in Nature Genetics.

The researchers found that people in the study with the variant MLH1 had a 40 percent lifetime risk of getting colon cancer, as compared to a 6 percent risk for the general population.

In Israel, where the study was conducted, colorectal cancer rates are among the highest in the world. Over the past three years, Lipkin and Gruber’s research team has been conducting a genetic epidemiological survey of colon cancer patients in northern Israel. They found that more than one percent carried the mutation, MLH1 D132H. The patients had no other risk factors, and could not be identified with one particular ethnic, cultural, or religious group, the researchers reported.

“We found the gene in a wide patient population of Sephardic and Ashkenazi Jews, Muslim and Christian Arabs, Druze Christians and Bedouins,” said Lipkin. “This leads us to believe that the population carrying this genetically variant gene is not limited to Israel, and this variant may have arisen during early phases of human evolutionary population migration. Although their numbers may be small, the people who have this specific genetic risk factor can be living anywhere in the world, and the odds of them getting colon cancer someday are very high.”

The researchers also said they developed new genetic screening tools to identify variant genes. Lipkin will use these tools to work with UCI’s Genetic Epidemiology Research Institute in order to survey colon cancer patients in other ethnic groups for this mutation.

—KL

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