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Repair Defects Linked to Risk of Familial Colorectal Cancer

-- A. Agrawal, PhD

Thursday, March 26, 2009

THURSDAY, March 26 (HealthDay News) -- The risk of colorectal cancer in first-degree relatives of colorectal cancer patients increases if the tumors are defective in repairing their DNA and if patients developed disease early, but most of the excess risk cannot be accounted for by defects in known genes, according to research published online March 23 in the Journal of Clinical Oncology.

Steven J. Lubbe, and colleagues from the Institute of Cancer Research in Sutton, United Kingdom, assessed DNA mismatch repair through microsatellite instability and the presence of two variants of the MUTYH gene in 2,941 patients with colorectal cancer.

The researchers found that first-degree relatives of colorectal cancer patients had a higher risk of colorectal cancer if the patient had microsatellite instability (standardized incidence ratio, 4.28), early-onset disease (SIR, 10.96 for microsatellite instability in patients under 55 years old), or more than one affected first-degree relative (SIR, 10.0 for microsatellite instability). However, the authors note that 69 percent of the excess familial risk of colorectal cancer in first-degree relatives is associated with microsatellite stable tumors. Only five patients had mutations in MUTYH and all had microsatellite stable tumors, the report indicates.

"Stratifying colorectal cancer by microsatellite instability status provides a powerful method of delineating familial patients with different risk profiles, and screening programs should take this information into account," Lubbe and colleagues conclude. "The observation that approximately two-thirds of the excess familial risk is unaccounted for by known genes provides a strong rationale for directing research to familial microsatellite stable cancer to identify novel colorectal cancer susceptibility genes."

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Specialties Cardiology
Diabetes & Endocrinology
Internal Medicine
Family Practice

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