title: Age-Dependent Cancer Risk Is Not Different in between MSH2 and MLH1 Mutation Carriers.
abstract: Lynch syndrome is mostly characterized by early-onset colorectal and endometrial adenocarcinomas. Over 90% of the causal mutations occur in two mismatch repair genes, MSH2 and MLH1. The aim of this study was to evaluate the age-dependent cancer risk in MSH2 or MLH1 mutation carriers from data of DNA diagnostic laboratories. To avoid overestimation, evaluation was based on the age-dependent proportion of mutation carriers in asymptomatic first-degree relatives of identified mutation carriers. Data from 859 such eligible relatives were collected from 8 centers; 387 were found to have inherited the mutation from their relatives. Age-dependent risks were calculated either using a nonparametric approach for four discrete age groups or assuming a modified Weibull distribution for the dependence of risk on age. Cancer risk was estimated starting at 28 (25-32 0.68 confidence interval) and to reach near 0.70 at 70 years. The risks were very similar for MSH2 and MLH1 mutation carriers. Although not statistically significant, the risk in males appeared to precede that for females by ten years. This difference needs to be investigated on a larger dataset. If confirmed, this would indicate that the onset of the colonoscopic surveillance may be different in male and female mutation carriers.
authors.affiliation: Institut National de la Santé et de la Recherche Médicale (INSERM), Unité 891, Centre de Recherches en Cancérologie de Marseille, 13009 Marseille, France.
authors.forename: Sylviane
authors.initials: S
authors.lastname: Olschwang
authors.forename: Kai
authors.initials: K
authors.lastname: Yu
authors.forename: Christine
authors.initials: C
authors.lastname: Lasset
authors.forename: Stéphanie
authors.initials: S
authors.lastname: Baert-Desurmont
authors.forename: Marie-Pierre
authors.initials: MP
authors.lastname: Buisine
authors.forename: Qing
authors.initials: Q
authors.lastname: Wang
authors.forename: Pierre
authors.initials: P
authors.lastname: Hutter
authors.forename: Etienne
authors.initials: E
authors.lastname: Rouleau
authors.forename: Olivier
authors.initials: O
authors.lastname: Caron
authors.forename: Violaine
authors.initials: V
authors.lastname: Bourdon
authors.forename: Gilles
authors.initials: G
authors.lastname: Thomas
references.citation: Cancer. 1993 Feb 1;71(3):677-85
references.pmid: 8431847
references.citation: Cancer Res. 2000 Jun 1;60(11):2760-3
references.pmid: 10850409
references.citation: J Natl Cancer Inst. 2006 Dec 6;98(23):1675-7
references.pmid: 17148764
references.citation: Gastroenterology. 1996 Apr;110(4):1020-7
references.pmid: 8612988
references.citation: J Med Genet. 2007 Jun;44(6):353-62
references.pmid: 17327285
references.citation: JAMA. 2006 Sep 27;296(12):1507-17
references.pmid: 17003399
references.citation: J Med Genet. 2003 Mar;40(3):208-13
references.pmid: 12624141
references.citation: J Clin Oncol. 2000 Jun;18(11):2193-200
references.pmid: 10829038
references.citation: J Med Genet. 2000 Sep;37(9):641-5
references.pmid: 10978352
references.citation: Hum Mol Genet. 1997 Jan;6(1):105-10
references.pmid: 9002677
references.citation: Int J Cancer. 1999 Apr 12;81(2):214-8
references.pmid: 10188721
references.citation: Clin Genet. 2008 Sep;74(3):233-42
references.pmid: 18554281
references.citation: J Med Genet. 2005 Jun;42(6):491-6
references.pmid: 15937084
references.citation: Hum Hered. 2008;66(4):238-51
references.pmid: 18612208
references.citation: Stat Med. 2007 Apr 15;26(8):1775-87
references.pmid: 17243094
references.citation: Gastroenterology. 1999 Jun;116(6):1453-6
references.pmid: 10348829