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New Model Identifies Mutations in Colorectal Cancer

In newly diagnosed colorectal cancer patients, model has high positive predictive value

WEDNESDAY, June 28 (HealthDay News) -- A new predictive model developed by multivariate logistic regression accurately identifies patients with colorectal cancer who are carriers of mutations in DNA repair genes, according to a study published in the June 29 issue of the New England Journal of Medicine.

Rebecca A. Barnetson, Ph.D., of the University of Edinburgh in the U.K., and colleagues applied the model to 870 newly diagnosed colorectal cancer patients under age 55. Stage 1 of the model incorporated only clinical variables while stage 2 consisted of tumor analysis by immunohistochemical staining and tests for microsatellite instability. The researchers also analyzed 2,938 patient-years of follow-up to see if genotype influenced survival.

The researchers found mutations in 38 (4 percent) of the patients, including 15 mutations in MLH1, 16 in MSH2, and seven in MSH6. Men were twice as likely to be carriers as women (6 percent versus 3 percent). They also found that the addition of immunohistochemical analysis in stage 2 of the model had a sensitivity of 62 percent and a positive predictive value of 80 percent.

"The performance of the model was robust among a wide range of cutoff probabilities and was superior to that of the Bethesda and Amsterdam criteria for hereditary non-polyposis colorectal cancer," the authors state. "Survival among carriers was not significantly different from that among non-carriers."

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