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Cancer Health Center

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Genetics of Colorectal Cancer (PDQ®): Genetics - Health Professional Information [NCI] - Major Genetic Syndromes

Table 10. Clinical Practice Guidelines for Colon Surveillance of BiallelicMYH-Associated Polyposis (MAP) continued...

These data have been largely retrospective and potentially include some biases for that reason. Some prospective data exist, however. The Colon Cancer Family Registry program followed 446 carriers prospectively and found a 10-year risk of CRC of 8%.[231]

Patients with LS can have synchronous and metachronous colorectal neoplasms and other primary extracolonic malignancies. LS mutation carriers have an increased risk of developing colon adenomas (hazard ratio [HR], 3.4), and the onset of adenomas appears to occur at a younger age than in nonmutation carriers from the same families.[232] Unlike patients with sporadic cancers, whose cancer develops most often in the left side of the colon, approximately two-thirds of LS cancers develop in the right side of the colon, defined as proximal to the splenic flexure.

The most common extracolonic malignancy in LS is endometrial adenocarcinoma, which affects at least one female member in about 50% of LS pedigrees. Fifty percent of women with a MMR gene mutation will present with endometrial cancer as their first malignancy.[233]

The lifetime risk of endometrial cancer has been estimated to be from 44% in MLH1 mutation carriers to 71% in MSH2 mutation carriers.[225,226,227,228,234] Families with an MSH6 mutation have been reported to have an endometrial cancer predominance. Lifetime risk of endometrial cancer in MSH6 mutation carriers in 113 families was estimated to be 26% at age 70 years and 44% at age 80 years.[228] In PMS2 mutation carriers, the endometrial cancer risk at age 70 years has been reported to be 15%.[229] The same prospective data collection in the Colon Cancer Family Registry program yielded 5-year endometrial cancer risks of about 3% and 10-year endometrial cancer risks of about 10% in women from this cohort.[231] Women with loss of MSH2 protein expression caused by an EPCAM mutation are also at risk of endometrial cancer. One study found a 12% (95% CI, 0%-27%) cumulative risk of endometrial cancer in EPCAM deletion carriers.[235] A study of 127 women with LS who had endometrial cancer as their index cancer were found to be at significantly increased risk of other cancers. The following elevated risks were reported: CRC, 48% (95% CI, 27.2%-58.3%); kidney, renal pelvis, and ureter cancer, 28% (95% CI, 11.9%-48.6%); urinary bladder cancer, 24.3% (95% CI, 8.56%-42.9%; and breast cancer, 2.51% (95% CI, 1.17%-4.14%).[236]

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