Hereditary cancer syndromes highly prevalent in young adults with colorectal cancer

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A missed opportunity

Dr. Barbara Jung

Early-age colorectal cancer is on the rise and, commonly, no genetic syndrome can be found. However, this study is a reminder that comprehensive genetic testing and counseling should be undertaken before coming to that conclusion. While Lynch syndrome is rare in MSI-negative tumors, it can occur and when missed not only dramatically affects the management of the patient, but also presents a missed opportunity to detect affected relatives.

The field of cancer genetics is evolving rapidly, and diagnostic tests are vastly expanding. When to order what test and, most importantly, how to interpret results as complex as genetic panels need expert involvement more than ever. It needs to be emphasized, however, that the majority of early cancers that do not meet criteria for a hereditary syndrome will not fit into any known genetic category. Nevertheless, this paper reinforces the notion that if a genetic cancer syndrome is suspected despite the lack of family history or other typical risk stratification, refer or seek advice early. This will also allow for us to better understand young patients with aggressive colon cancer outside of genetic syndromes.

Dr. Barbara Jung is associate professor of medicine, chief of the division of gastroenterology and hepatology, University of Illinois at Chicago. She has no conflicts of interest.




Patients diagnosed with colorectal cancer at a younger age are more likely to have hereditary cancer syndromes, according to a study published online in the Journal of Clinical Oncology.

About one-third of patients who were diagnosed with colorectal cancer (CRC) at age 35 years or younger had a hereditary cancer syndrome, which is much higher than the 2%-5% rate seen in the general CRC population.

“Our results support a referral to genetic counseling for hereditary cancer syndromes for all patients diagnosed with CRC at 35 years or younger, regardless of family history of CRC, even when patients have normal MSI [microsatellite instability] and IHC [immunohistochemistry] tumor study results,” wrote Maureen Mork and colleagues from the University of Texas MD Anderson Cancer, Houston (J. Clin. Oncol. 2015 July 20).

Many of the patients with hereditary syndromes had no family history of CRC, and they represented both de novo mutations and incomplete penetrance. Among 67 patients in the hereditary group, about 23 were diagnosed with Lynch syndrome (LS), 22 with mutation-negative LS, and 20 presented with a familial adenomatous polyposis (FAP) phenotype.

Patients without a hereditary syndrome had more frequent left-sided colon tumors, metastatic disease, and poor differentiation, compared with the hereditary group. Differences in disease stage at diagnosis may have resulted from increased surveillance among those with family history of disease.

Revised Bethesda guidelines recommend testing patients for LS, but the authors support broader evaluation because the hereditary syndromes observed in the study were not limited to LS. Adolescent and young adult patients with CRC may benefit from having “comprehensive hereditary CRC genetic testing panels, especially in the absence of a clinical phenotype or with normal MSI and IHC tumor studies,” they wrote.

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