title: Risks of less common cancers in proven mutation carriers with lynch syndrome.
abstract: OBJECTIVE
  Patients with Lynch syndrome are at high risk for colon and endometrial cancer, but also at an elevated risk for other less common cancers. The purpose of this retrospective cohort study was to provide risk estimates for these less common cancers in proven carriers of pathogenic mutations in the mismatch repair (MMR) genes MLH1, MSH2, and MSH6.
  
  
  METHODS
  Data were pooled from the German and Dutch national Lynch syndrome registries. Seven different cancer types were analyzed: stomach, small bowel, urinary bladder, other urothelial, breast, ovarian, and prostate cancer. Age-, sex- and MMR gene-specific cumulative risks (CRs) were calculated using the Kaplan-Meier method. Sex-specific incidence rates were compared with general population incidence rates by calculating standardized incidence ratios (SIRs). Multivariate Cox regression analysis was used to estimate the impact of sex and mutated gene on cancer risk.
  
  
  RESULTS
  The cohort comprised 2,118 MMR gene mutation carriers (MLH1, n = 806; MSH2, n = 1,004; MSH6, n = 308). All cancers were significantly more frequent than in the general population. The highest risks were found for male small bowel cancer (SIR, 251; 95% CI, 177 to 346; CR at 70 years, 12.0; 95% CI, 5.7 to 18.2). Breast cancer showed an SIR of 1.9 (95% CI, 1.4 to 2.4) and a CR of 14.4 (95% CI, 9.5 to 19.3). MSH2 mutation carriers had a considerably higher risk of developing urothelial cancer than MLH1 or MSH6 carriers.
  
  
  CONCLUSIONS
  The sex- and gene-specific differences of less common cancer risks should be taken into account in cancer surveillance and prevention programs for patients with Lynch syndrome.
authors.affiliation: University of Leipzig, Leipzig, Germany. christoph.engel@imise.uni-leipzig.de
authors.forename: Christoph
authors.initials: C
authors.lastname: Engel
authors.forename: Markus
authors.initials: M
authors.lastname: Loeffler
authors.forename: Verena
authors.initials: V
authors.lastname: Steinke
authors.forename: Nils
authors.initials: N
authors.lastname: Rahner
authors.forename: Elke
authors.initials: E
authors.lastname: Holinski-Feder
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Dietmaier
authors.forename: Hans K
authors.initials: HK
authors.lastname: Schackert
authors.forename: Heike
authors.initials: H
authors.lastname: Goergens
authors.forename: Magnus
authors.initials: M
authors.lastname: von Knebel Doeberitz
authors.forename: Timm O
authors.initials: TO
authors.lastname: Goecke
authors.forename: Wolff
authors.initials: W
authors.lastname: Schmiegel
authors.forename: Reinhard
authors.initials: R
authors.lastname: Buettner
authors.forename: Gabriela
authors.initials: G
authors.lastname: Moeslein
authors.forename: Tom G W
authors.initials: TG
authors.lastname: Letteboer
authors.forename: Encarna
authors.initials: E
authors.lastname: Gómez García
authors.forename: Frederik J
authors.initials: FJ
authors.lastname: Hes
authors.forename: Nicoline
authors.initials: N
authors.lastname: Hoogerbrugge
authors.forename: Fred H
authors.initials: FH
authors.lastname: Menko
authors.forename: Theo A M
authors.initials: TA
authors.lastname: van Os
authors.forename: Rolf H
authors.initials: RH
authors.lastname: Sijmons
authors.forename: Anja
authors.initials: A
authors.lastname: Wagner
authors.forename: Irma
authors.initials: I
authors.lastname: Kluijt
authors.forename: Peter
authors.initials: P
authors.lastname: Propping
authors.forename: Hans F A
authors.initials: HF
authors.lastname: Vasen
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics; D000328:Adult; D000368:Aged; D015331:Cohort Studies; D003123:Colorectal Neoplasms, Hereditary Nonpolyposis / Q000453:epidemiology* / Q000235:genetics*; D004268:DNA-Binding Proteins / Q000235:genetics; D005260:Female; D005858:Germany / Q000453:epidemiology; D006801:Humans; D008297:Male; D008875:Middle Aged; D000070957:MutL Protein Homolog 1; D051718:MutS Homolog 2 Protein / Q000235:genetics; D009154:Mutation; D009369:Neoplasms / Q000453:epidemiology* / Q000235:genetics*; D009426:Netherlands / Q000453:epidemiology; D009687:Nuclear Proteins / Q000235:genetics; D012042:Registries; D012189:Retrospective Studies; D012307:Risk Factors
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D004268:DNA-Binding Proteins; C094443:G-T mismatch-binding protein; C501486:MLH1 protein, human; D009687:Nuclear Proteins; C497172:MSH2 protein, human; D000070957:MutL Protein Homolog 1; D051718:MutS Homolog 2 Protein