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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...

LS-associated endometrial cancer is not limited to the endometrioid subtype. It most commonly arises from the lower uterine segment. Endometrial adenocarcinoma, clear cell carcinoma, uterine papillary serous carcinoma, and malignant mixed Müllerian tumors are part of the spectrum of uterine tumors in LS.[237] Three cases of endometrial cancer arising from endometriosis in women with LS have been reported.[238] (Refer to the Screening for endometrial cancer in LS families section of this summary for information about screening methods.)

Several studies have demonstrated that patients with LS are also at risk of developing transitional cell carcinoma of the ureters and renal pelvis and cancers of the stomach, small intestine, liver and biliary tract, brain, breast, ovary, prostate, and adrenal cortex.[239,240,241,242,243,244,245] The largest prospective study to date is of 446 unaffected mutation carriers from the Colon Cancer Family Registry.[231] Participants who were followed for up to 10 years demonstrated an increased standardized incidence ratio (SIR) for colorectal, endometrial, ovarian, gastric, renal, bladder, pancreatic, and breast cancers.[231] With the exception of colorectal, endometrial, and breast cancers, the number of observed cases was very small for most cancers (i.e., two to three cases), resulting in very wide 95% CIs.

The issue of breast cancer risk in LS has been controversial. Retrospective studies have been inconsistent, but several have demonstrated microsatellite instability in a proportion of breast cancers from individuals with LS;[246,247,248,249] one of these studies evaluated breast cancer risk in individuals with LS and found that it is not elevated.[249] However, the largest prospective study to date of 446 unaffected mutation carriers from the Colon Cancer Family Registry [231] who were followed for up to 10 years reported an elevated SIR of 3.95 for breast cancer (95% CI, 1.59-8.13; P = .001).[231] The same group subsequently analyzed data on 764 MMR gene mutation carriers with a prior diagnosis of colorectal cancer. Results showed that the 10-year risk of breast cancer following colorectal cancer was 2% (95% CI, 1%-4%) and that the SIR was 1.76 (95% CI, 1.07-2.59).[250] However, further studies are needed to define absolute risks and age distribution before surveillance guidelines for breast cancer can be developed for MMR mutation carriers.

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