2012 Clinicopathological Features and Management of Cancers in Lynch Syndrome (easy to read)

Blogger's Note: nice, easy to read paper

Clinicopathological Features and Management of Cancers in Lynch Syndrome

Abstract
Lynch syndrome (LS) is characterized by an autosomal dominant inheritance of the early onset of colorectal cancer (CRC) and endometrial cancer, as well as increased risk for several other cancers including gastric, urinary tract, ovarian, small bowel, biliary tract, and brain tumors. The syndrome is due to a mutation in one of the four DNA mismatch repair (MMR) genes MLH1, MSH2, MSH6, or PMS2. The majority of LS patients and families can now be identified, and the underlying mutation detected using genetic diagnostics. Regular surveillance for CRC and endometrial cancer has proved beneficial for mutation carriers. However, screening for other tumors is also recommended even though experiences in the screening of these tumors is limited. Prophylactic colectomy, prophylactic hysterectomy, and bilateral salpingo-oophorectomy may be reasonable options for selected patients with LS. This paper describes the features and management of LS.

1. Introduction (The syndrome is due to a mutation in one of the four DNA mismatch repair (MMR) genes MLH1, MSH2, MSH6, or PMS2.)

2. Genetic Characteristics of Lynch Syndrome
3. Identification of Lynch Syndrome
4. Tumor Spectrum of Lynch Syndrome
5. Colorectal Cancer (>MLH1 and MSH2; <MSH6;)
6. Endometrial Cancer (MSH6 mutations are at higher risk)
7. Gastric Cancer (seems to be not different between different mutations)
8. Uroepithelial and Kidney Cancers (predominately MSH2)
9. Other Tumors

• 9.1. Ovarian Cancer        Ovarian cancer has been shown to occur in excess in LS. Two Finnish studies [5, 45] have shown a lifetime risk for ovarian cancer in LS ranging between 9% and 12% compared to 1.3% in the general population. Recently, Watson et al. [6] reported a lifetime risk of 7% in a large series from four LS research centers. They also found that MSH2 family members had nearly twice the incidence rate observed in MLH1 family members, and the highest risk period for ovarian cancer was from age 40 to 55 years. Ovarian cancer in LS seems to have a better prognosis than that in the general population or in BRCA1/2 mutation carriers [59]. Information currently available is too limited to assess whether screening for ovarian cancer in LS mutation carriers has any advantages.

• 9.2. Carcinomas of the Biliary Tract and Pancreas (duodenum/jejunum)
• 9.3. Brain Tumors (higher in MSH2 than in MLH1)

10. Conclusions

 (ovarian) reference: 
59.  E. M. Grindedal, L. Renkonen-Sinisalo, H. Vasen et al., “Survival in women with MMR mutations and ovarian cancer: a multicentre study in Lynch syndrome kindreds,” Journal of Medical Genetics, vol. 47, no. 2, pp. 99–102, 2010. View at Publisher · View at Google Scholar · View at Scopus