Skip to content

Cancer Health Center

Font Size

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

Table 8. Clinical Practice Guidelines for Diagnosis and Colon Surveillance of Familial Adenomatous Polyposis (FAP) continued...

The lifetime risk of CRC in MLH1 and MSH2 mutation carriers was 68.7% in males and 52% in females.[215] However, in a meta-analysis of three population-based studies and one clinic-based study, the lifetime risk of CRC in MLH1 and MSH2 mutation carriers was reported to be 53% in males and 33% in females.[216,217] In a study of 113 families with MSH6 mutation carriers, the estimated cumulative risk of CRC in males was 22% and 10% in females.[218]PMS2 lifetime CRC risk to age 70 years has been reported to be 20% in males and 15% in females.[219] A large registry-based study from France estimated CRC risk at age 70 years to be 41% for MLH1 mutation carriers, 48% for MSH2 mutation carriers, and 12% for MSH6 mutation carriers.[220]

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%.[221]

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.[222] 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.

In addition to CRC, LS patients and their relatives are at risk of a wide variety of other cancers. The most common is endometrial adenocarcinoma, which affects at least one female member in about 50% of LS pedigrees. The lifetime risk of endometrial cancer in MLH1 and MSH2 mutation carriers has been estimated at 44% to 54%.[215,216,217,218] Families with a 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.[218] In PMS2 mutation carriers, the endometrial cancer risk at age 70 years has been reported to be 15%.[219] The same prospective data collection in the Colon Cancer Family Registry program yielded 5- and 10-year endometrial cancer risks of about 3% and 10%, respectively, in women from this cohort.[221] Endometrial cancer can be the index cancer in female LS patients. LS-associated endometrial cancer is not limited to the endometrioid subtype. Endometrial adenocarcinoma, clear cell carcinoma, uterine papillary serous carcinoma, and malignant mixed Müllerian tumors are part of the spectrum of uterine tumors in LS.[223]

Next Article:

Today on WebMD

Colorectal cancer cells
A common one in both men and women.
Lung cancer xray
See it in pictures, plus read the facts.
sauteed cherry tomatoes
Fight cancer one plate at a time.
Ovarian cancer illustration
Do you know the symptoms?
Jennifer Goodman Linn self-portrait
what is your cancer risk
colorectal cancer treatment advances
breast cancer overview slideshow
prostate cancer overview
lung cancer overview slideshow
ovarian cancer overview slideshow
Actor Michael Douglas