A screen for mutations in mismatch repair (MMR) genes could be used to identify young people at risk for colorectal cancer, report Paul Limburg et al. in the June issue of Clinical Gastroenterology and Hepatology.
It is a challenge to identify people who are less than 50 years old that have colorectal cancer—they account for only 6.5% of all cases. Lynch syndrome, a young-onset form of cancer of the colorectum (and other organs) is caused by germline defects in MMR genes, whose products repair damaged DNA; cancer-causing mutations occur most frequently in MLH1, MSH2, or MSH6. Although algorithms, molecular tests, and statistical models have been developed to identify people most likely to develop the syndrome, it is still frequently detected at late stages, when it is hard to treat.
Limburg et al. analyzed DNA from 195 patients who developed colorectal cancer at an average age of 43 years; 5.6% of the patients had mutations in MLH1, MSH2, or MSH6 that were sufficient to cause the disease, and gene variants of uncertain significance were found in 7.2% of patients. About 36% of cases had a family history of CRC. Limburg et al. observed that prevalence of germline MMR mutations in this population of young patients is higher than in CRC patients overall.
Hospitals are increasing tests of CRC patients for various mutations and other genetic features, with or without selection based on age. In an accompanying editorial, Patrick Lynch says that testing all patients with CRC for MMR gene and other mutations would help identify those with family members at risk for young-onset CRC. However, additional markers or CRC risk are needed.
Limburg et al. observed that 12% of cases had lost expression of MMR gene products, based on immunohistochemical analysis—the presence or absence of protein was a good predictor of whether patients carried mutations in mismatch repair genes. Lynch states that immunohistochemistry might be used as a first step to identify patients that should be tested for germline mutations in MMR genes.
More Information on Colorectal Cancer:
- The National Cancer Institute Colorectal Cancer Screening Fact Sheet
- CDC Website on Colorectal Cancer Screening
Read the article online.
Limburg PJ, Harmsen WS, Chen HH, et al. Prevalence of alterations in DNA mismatch repair genes in patients with young-onset colorectal cancer. Clin Gastroenterol and Hepatol 2011;9:497–502.
Read the accompanying editorial.
Lynch, PM. How helpful is age at colorectal cancer onset in finding hereditary nonpolyposis colorectal cancer? Clin Gastroenterol and Hepatol 2011;9:458–460.