Table 8. Clinical Practice Guidelines for Diagnosis and Colon Surveillance of Familial Adenomatous Polyposis (FAP) continued...
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, and ovary.[219,220,221,222,223] The largest prospective study to date is of 446 unaffected mutation carriers from the Colon Cancer Family Registry. 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. 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% confidence intervals.
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;[224,225,226,227] one of these studies evaluated breast cancer risk in individuals with LS and found that it is not elevated. However, the largest prospective study to date of 446 unaffected mutation carriers from the Colon Cancer Family Registry  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). 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). 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.
Muir-Torre syndrome is considered a variant of LS and includes a phenotype of multiple cutaneous neoplasms (including sebaceous adenomas, sebaceous carcinomas, and keratoacanthomas). The skin lesions and CRC define the phenotype,[229,230] and clinical variability is common. Both mutations in the MSH2 and MLH1 genes have been found in Muir-Torre families.[231,232,233] A study of 1,914 MSH2 and MLH1 unrelated probands found MSH2 to be more common in individuals with the Muir-Torre syndrome phenotype.
Criteria for defining LS families
The research criteria for defining LS families were established by the International Collaborative Group (ICG) meeting in Amsterdam in 1990, and are known as the Amsterdam criteria.
- One member diagnosed with CRC before age 50 years.
- Two affected generations.
- Three affected relatives, one of them a first-degree relative of the other two.
- FAP should be excluded.
- Tumors should be verified by pathological examination.