BACKGROUND: Lynch syndrome (or HNPCC) is a colorectal cancer syndrome caused by germline mutations in either one of the DNA mismatch repair (MMR) genes hMLH1, hMSH2, hMSH6 or hPMS2. Mutations in hMLH1 and hMSH2 are most prevalent. Here we aimed to determine the cancer risk of MMR gene mutation carriers and, in addition, the efficacy of colonoscopy surveillance in Chinese Lynch syndrome family members with and without MMR gene mutations. METHODS: A Lynch syndrome family registry encompassing 106 families in Northern China was recently established. Detailed pedigree data for each family were collected and hMLH1 and hMSH2 gene mutation analyses were performed. Germ-line mutations were identified in probands from 42 of these families, and additional genetic analyses were performed in each member of these 42 families to identify mutation and non-mutation carriers. Among the family members included, 180 received colonoscopy and the remaining cases were followed without colonoscopy. RESULTS: Overall 54.8 % of the Lynch syndrome family members carried MMR gene mutations, and these mutation carriers exhibited significantly higher colorectal cancer and other Lynch syndrome-associated cancer risks as compared to non-mutation carriers. The cumulative risk for all Lynch syndrome-related cancers at age 70 was 93.8 % for both hMLH1 and hMSH2 mutation carriers, and 81.7 % and 93.1 % for colorectal cancer at this age, respectively. Whereas 43 of 102 (42.2 %) mutation carriers exhibited significant colonoscopy findings, including 10 colorectal cancers, none of 78 non-mutation carriers exhibited significant findings, and no cancers were detected. In addition, in the mutation carriers, colonoscopy surveillance led to the detection of more early stage cancers than in the non-surveillance group (70.0 % versus 36.5 %, p < 0.01). CONCLUSION: In Lynch syndrome family members, we recommend pre-symptomatic MMR gene mutation analysis in order to identify high risk individuals for colonoscopy surveillance.
BACKGROUND:Lynch syndrome (or HNPCC) is a colorectal cancer syndrome caused by germline mutations in either one of the DNA mismatch repair (MMR) genes hMLH1, hMSH2, hMSH6 or hPMS2. Mutations in hMLH1 and hMSH2 are most prevalent. Here we aimed to determine the cancer risk of MMR gene mutation carriers and, in addition, the efficacy of colonoscopy surveillance in Chinese Lynch syndrome family members with and without MMR gene mutations. METHODS: A Lynch syndrome family registry encompassing 106 families in Northern China was recently established. Detailed pedigree data for each family were collected and hMLH1 and hMSH2 gene mutation analyses were performed. Germ-line mutations were identified in probands from 42 of these families, and additional genetic analyses were performed in each member of these 42 families to identify mutation and non-mutation carriers. Among the family members included, 180 received colonoscopy and the remaining cases were followed without colonoscopy. RESULTS: Overall 54.8 % of the Lynch syndrome family members carried MMR gene mutations, and these mutation carriers exhibited significantly higher colorectal cancer and other Lynch syndrome-associated cancer risks as compared to non-mutation carriers. The cumulative risk for all Lynch syndrome-related cancers at age 70 was 93.8 % for both hMLH1 and hMSH2 mutation carriers, and 81.7 % and 93.1 % for colorectal cancer at this age, respectively. Whereas 43 of 102 (42.2 %) mutation carriers exhibited significant colonoscopy findings, including 10 colorectal cancers, none of 78 non-mutation carriers exhibited significant findings, and no cancers were detected. In addition, in the mutation carriers, colonoscopy surveillance led to the detection of more early stage cancers than in the non-surveillance group (70.0 % versus 36.5 %, p < 0.01). CONCLUSION: In Lynch syndrome family members, we recommend pre-symptomatic MMR gene mutation analysis in order to identify high risk individuals for colonoscopy surveillance.
Authors: Elena M Stoffel; Rowena C Mercado; Wendy Kohlmann; Beth Ford; Shilpa Grover; Peggy Conrad; Amie Blanco; Kristen M Shannon; Mark Powell; Daniel C Chung; Jonathan Terdiman; Stephen B Gruber; Sapna Syngal Journal: Am J Gastroenterol Date: 2010-03-30 Impact factor: 10.864
Authors: D J Peel; A Ziogas; E A Fox; M Gildea; B Laham; E Clements; R D Kolodner; H Anton-Culver Journal: J Natl Cancer Inst Date: 2000-09-20 Impact factor: 13.506
Authors: Hans F A Vasen; Mohamed Abdirahman; Richard Brohet; Alexandra M J Langers; Jan H Kleibeuker; Mariette van Kouwen; Jan Jacob Koornstra; Henk Boot; Annemieke Cats; Evelien Dekker; Silvia Sanduleanu; Jan-Werner Poley; James C H Hardwick; Wouter H de Vos Tot Nederveen Cappel; Andrea E van der Meulen-de Jong; T Gie Tan; Maarten A J M Jacobs; Faig Lall A Mohamed; Sijbrand Y de Boer; Paul C van de Meeberg; Marie-Louise Verhulst; Jan M Salemans; Nico van Bentem; B Dik Westerveld; Juda Vecht; Fokko M Nagengast Journal: Gastroenterology Date: 2010-03-02 Impact factor: 22.682
Authors: Sidney J Winawer; Ann G Zauber; Robert H Fletcher; Jonathon S Stillman; Michael J O'Brien; Bernard Levin; Robert A Smith; David A Lieberman; Randall W Burt; Theodore R Levin; John H Bond; Durado Brooks; Tim Byers; Neil Hyman; Lynne Kirk; Alan Thorson; Clifford Simmang; David Johnson; Douglas K Rex Journal: Gastroenterology Date: 2006-05 Impact factor: 22.682
Authors: J Q Sheng; L Fu; Z Q Sun; J S Huang; M Han; H Mu; H Zhang; Y Z Zhang; M Z Zhang; A Q Li; Z T Wu; Y Han; S R Li Journal: Cytogenet Genome Res Date: 2008-10-14 Impact factor: 1.636