The Risk of Extra-colonic, Extra-endometrial Cancer in the Lynch Syndrome

By P. Watson, H. Vasen, J. Mecklin, I. Bernstein, M. Aarnio, H. Järvinen, T. Myrhøj, L. Sunde, J. Wijnen, Henry T. Lynch. International Journal of Cancer, 2008

611 citations recorded by the source corpus.

Persons with the Lynch syndrome (LS) are at high risk for cancer, including cancers of the small bowel, stomach, upper urologic tract (renal pelvis and ureter), ovary, biliary tract and brain tumors, in addition to the more commonly observed colorectal and endometrial cancers. Cancer prevention strategies for these less common cancers require accurate, age‐specific risk estimation. We pooled data from 4 LS research centers in a retrospective cohort study, to produce absolute incidence estimates for these cancer types, and to evaluate several potential risk modifiers. After elimination of 135 persons missing crucial information, cohort included 6,041 members of 261 families with LS‐associated MLH1 or MSH2 mutations. All were either mutation carriers by test, probable mutation carriers (endometrial/colorectal cancer‐affected), or first‐degree relatives of these. Among mutation carriers and probable carriers, urologic tract cancer (N = 98) had an overall lifetime risk (to age 70) of 8.4% (95% CI: 6.6–10.8); risks were higher in males (p < 0.02) and members of MSH2 families (p < 0.0001). Ovarian cancer (N = 72) had an lifetime risk of 6.7% (95% CI: 5.3–9.1); risks were higher in women born after the median year of birth (p < 0.008) and in members of MSH2 families (p < 0.006). Brain tumors and cancers of the small bowel, stomach, breast and biliary tract were less common. Urologic tract cancer and ovarian cancer occur frequently enough in some LS subgroups to justify trials to evaluate promising prevention interventions. Other cancer types studied occur too infrequently to justify strenuous cancer control interventions. © 2008 Wiley‐Liss, Inc.

Subfields: Cancer Research, Oncology, Pathology and Forensic Medicine

View Paper: https://www.semanticscholar.org/paper/5289a248cb3c1874bffcd96f432e489660ded97a

Citations in the corpus

• Review of the Lynch syndrome: history, molecular genetics, screening, differential diagnosis, and medicolegal ramifications (2009, neutral): “• Autosomal dominant inheritance pattern seen for syndrome cancers in the family pedigree • Earlier average age of colorectal cancer (CRC) onset than in the general population Average age of 45 years in LS vs 69 years in the general population • Proximal (right-sided) colonic cancer predilection ∼70”
• Revised guidelines for the clinical management of Lynch syndrome (HNPCC): recommendations by a group of European experts (2013, neutral): “There is no evidence for the clustering of small bowel cancer in specific families.(12) The tumours in LS families are mainly located in the proximal small bowel (43%) and the jejunum (33%); 7% are located in the ileum.”