title: Cancer risk in families with hereditary nonpolyposis colorectal cancer diagnosed by mutation analysis.
abstract: OBJECTIVE
  Hereditary nonpolyposis colorectal cancer is characterized by early-onset colorectal cancer and the occurrence of various other cancers. The recent isolation of four mismatch repair genes responsible for hereditary nonpolyposis colorectal cancer allows for the identification of carriers within affected families. The purpose of this study was to assess the age-specific cancer risk in a large series of gene carriers.
  
  
  METHODS
  Thirty-four families were studied by mutation analysis. In 19 of these families, pathogenic mutations were found at hMSH2 or hMLH1. Of 382 relatives, 124 had a mutation in hMLH1 and 86 in hMSH2.
  
  
  RESULTS
  The lifetime risk of colorectal cancer was the same in both groups of gene carriers (80%). The risk of endometrial cancer was greater in hMSH2 gene carriers compared with hMLH1 gene carriers (61% vs. 42%), but the difference was not statistically significant. A very high relative risk of cancer of the small bowel (relative risk of >100) was observed in carriers of either gene. Only the carriers of hMSH2 mutations had a significantly increased relative risk of cancer of the urinary tract (kidney and ureter) (relative risk of 75.3), stomach (relative risk of 19.3), and ovaries (relative risk of 8.0).
  
  
  CONCLUSIONS
  This study provides estimates of cancer risk that may contribute to the appropriate management of gene carriers within families with hereditary nonpolyposis colorectal cancer.
authors.affiliation: The Netherlands Foundation for the Detection of Hereditary Tumours, Leiden, The Netherlands.
authors.forename: H F
authors.initials: HF
authors.lastname: Vasen
authors.forename: J T
authors.initials: JT
authors.lastname: Wijnen
authors.forename: F H
authors.initials: FH
authors.lastname: Menko
authors.forename: J H
authors.initials: JH
authors.lastname: Kleibeuker
authors.forename: B G
authors.initials: BG
authors.lastname: Taal
authors.forename: G
authors.initials: G
authors.lastname: Griffioen
authors.forename: F M
authors.initials: FM
authors.lastname: Nagengast
authors.forename: E H
authors.initials: EH
authors.lastname: Meijers-Heijboer
authors.forename: L
authors.initials: L
authors.lastname: Bertario
authors.forename: L
authors.initials: L
authors.lastname: Varesco
authors.forename: M L
authors.initials: ML
authors.lastname: Bisgaard
authors.forename: J
authors.initials: J
authors.lastname: Mohr
authors.forename: R
authors.initials: R
authors.lastname: Fodde
authors.forename: P M
authors.initials: PM
authors.lastname: Khan
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D003123:Colorectal Neoplasms, Hereditary Nonpolyposis / Q000235:genetics*; D004252:DNA Mutational Analysis; D004260:DNA Repair / Q000235:genetics; D005192:Family Health; D005260:Female; D005796:Genes; D006579:Heterozygote; D006801:Humans; D007414:Intestinal Neoplasms / Q000235:genetics; D007421:Intestine, Small; D008297:Male; D008875:Middle Aged; D009154:Mutation; D010051:Ovarian Neoplasms / Q000235:genetics; D012306:Risk; D013274:Stomach Neoplasms / Q000235:genetics; D014571:Urologic Neoplasms / Q000235:genetics