Universal Tumor Testing to Identify Lynch Syndrome

Posted on October 30th, 2012 by

Universal tumor MMR testing among patients with colorectal cancer may have a greater sensitivity for identifying Lynch syndrome than other screening strategies, according to the results of a study published in the Journal of the American Medical Association.

Lynch Syndrome, also known as hereditary nonpolyposis colorectal cancer (HNPCC), results from inherited mutations in genes involved in DNA mismatch repair—called mismatch repair or MMR genes. These mutations greatly increase the risk of developing colorectal cancer. In individuals with Lynch Syndrome, the average age at diagnosis of colorectal cancer is about 44 years, compared with 64 years in the general population. Overall, roughly 3% to 5% of all colorectal cancers are thought to result from Lynch Syndrome. Other cancers that are more common in Lynch Syndrome families include cancers of the endometrium (the lining of the uterus), ovary, small intestine, ureter, and renal pelvis.

Researchers continue to develop tools for identifying individuals who are most likely to carry the inherited mutation for Lynch Syndrome. Currently, germline analysis is required to identify those who carry the gene; however, it is still unclear how to select individuals who should undergo tumor MMR testing.

There are two sets of guidelines used to identify families that may be at risk of Lynch Syndrome—the Amsterdam Criteria and the Bethesda Guidelines. Both sets of guidelines evaluate the family history as well as tumor characteristics—but some data has shown that the Bethesda Guidelines may be more sensitive. These guidelines are often used to determine whether genetic testing is necessary.

The guidelines are unreliable—some families with known Lynch Syndrome do not meet the criteria set out by the guidelines and other families with Lynch Syndrome are missed due to the poor sensitivity of the criteria—and as a result, some researchers have suggested a more universal approach to genetic testing—where all colorectal tumors are tested for the MMR gene.

To test this theory, researchers performed a pooled-data analysis of four large cohorts of newly diagnosed patients with colorectal cancer. The study included 10,206 patients recruited between 1994 and 2010 from the Colon Cancer Family Registry, the EPICOLON project, Ohio State University, and the University of Helsinki. The goal was to determine the sensitivity and efficiency of several different strategies for screening for Lynch Syndrome. They compared performance characteristics of guidelines such as the Bethesda Guidelines with universal screening—tumor MMR testing of all colorectal cancer patients.

The results indicated that universal tumor MMR testing among colorectal cancer patients had a greater sensitivity for identifying Lynch syndrome compared with several other strategies—but the researchers not that the increase in the diagnostic yield was modest. The results serve to highlight the limitations of the criteria used to identify Lynch syndrome. Universal tumor MMR testing could help identify individuals at increased risk of Lynch syndrome—leading to more screening and early detection and possibly a reduction in disease-specific mortality.


Moreira L, Balaguer F, Lindor N, et al. Identification of Lynch Syndrome among patients with colorectal cancer. Journal of the American Medical Association. 2012; 308(15): 1555-1565.

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Tags: Colon Cancer, News, Screening/Prevention Colon Cancer

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