title: Risks of colorectal and other cancers after endometrial cancer for women with Lynch syndrome.
abstract: BACKGROUND
  Lynch syndrome is an autosomal dominantly inherited disorder caused by germline mutations in DNA mismatch repair (MMR) genes. Previous studies have shown that MMR gene mutation carriers are at increased risk of colorectal, endometrial, and several other cancers following an initial diagnosis of colorectal cancer. We estimated cancer risks following an endometrial cancer diagnosis for women carrying MMR gene mutations.
  
  
  METHODS
  We obtained data from the Colon Cancer Family Registry for a cohort of 127 women who had a diagnosis of endometrial cancer and who carried a mutation in one of four MMR genes (30 carried a mutation in MLH1, 72 in MSH2, 22 in MSH6, and 3 in PMS2). We used the Kaplan-Meier method to estimate 10- and 20-year cumulative risks for each cancer. We estimated the age-, country-, and calendar period-specific standardized incidence ratios (SIRs) for each cancer, compared with the general population.
  
  
  RESULTS
  Following endometrial cancer, women carrying MMR gene mutations had the following 20-year risks of other cancer cancers: colorectal cancer (48%, 95% confidence interval [CI] = 35% to 62%); cancer of the kidney, renal pelvis, or ureter (11%, 95% CI = 3% to 20%); urinary bladder cancer (9%, 95% CI = 2% to 17%); and breast cancer (11%, 95% CI = 4% to 19%). Compared with the general population, these women were at statistically significantly elevated risks of colorectal cancer (SIR = 39.9, 95% CI = 27.2 to 58.3), cancer of the kidney, renal pelvis, or ureter (SIR = 28.3, 95% CI = 11.9 to 48.6), urinary bladder cancer (SIR = 24.3, 95% CI = 8.56 to 42.9), and breast cancer (SIR = 2.51, 95% CI = 1.17 to 4.14).
  
  
  CONCLUSIONS
  Women with Lynch syndrome who are diagnosed with endometrial cancer have increased risks of several cancers, including breast cancer.
authors: Centre for Molecular, Environmental, Genetic and Analytic Epidemiology, Melbourne School of Population Health, Level 3, 207 Bouverie St, University of Melbourne, VIC 3010 Australia.
authors: Aung Ko
authors: AK
authors: Win
authors: Noralane M
authors: NM
authors: Lindor
authors: Ingrid
authors: I
authors: Winship
authors: Katherine M
authors: KM
authors: Tucker
authors: Daniel D
authors: DD
authors: Buchanan
authors: Joanne P
authors: JP
authors: Young
authors: Christophe
authors: C
authors: Rosty
authors: Barbara
authors: B
authors: Leggett
authors: Graham G
authors: GG
authors: Giles
authors: Jack
authors: J
authors: Goldblatt
authors: Finlay A
authors: FA
authors: Macrae
authors: Susan
authors: S
authors: Parry
authors: Matthew F
authors: MF
authors: Kalady
authors: John A
authors: JA
authors: Baron
authors: Dennis J
authors: DJ
authors: Ahnen
authors: Loic Le
authors: LL
authors: Marchand
authors: Steven
authors: S
authors: Gallinger
authors: Robert W
authors: RW
authors: Haile
authors: Polly A
authors: PA
authors: Newcomb
authors: John L
authors: JL
authors: Hopper
authors: Mark A
authors: MA
authors: Jenkins
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics; D000251:Adenosine Triphosphatases / Q000235:genetics; D000328:Adult; D000368:Aged; D001943:Breast Neoplasms / Q000453:epidemiology; D015179:Colorectal Neoplasms / Q000453:epidemiology* / Q000235:genetics; D003123:Colorectal Neoplasms, Hereditary Nonpolyposis / Q000453:epidemiology* / Q000235:genetics; D053843:DNA Mismatch Repair / Q000235:genetics*; D045643:DNA Repair Enzymes / Q000235:genetics; D004268:DNA-Binding Proteins / Q000235:genetics; D016889:Endometrial Neoplasms / Q000453:epidemiology* / Q000235:genetics; D005260:Female; D018095:Germ-Line Mutation; D006579:Heterozygote; D006801:Humans; D015994:Incidence; D053208:Kaplan-Meier Estimate; D008875:Middle Aged; D000070976:Mismatch Repair Endonuclease PMS2; D000070957:MutL Protein Homolog 1; D051718:MutS Homolog 2 Protein / Q000235:genetics; D009369:Neoplasms / Q000453:epidemiology; D009687:Nuclear Proteins / Q000235:genetics; D012306:Risk; D012878:Skin Neoplasms / Q000453:epidemiology; D014571:Urologic Neoplasms / Q000453:epidemiology / Q000235:genetics
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D004268:DNA-Binding Proteins; C094443:G-T mismatch-binding protein; C501486:MLH1 protein, human; D009687:Nuclear Proteins; D000251:Adenosine Triphosphatases; C094934:PMS2 protein, human; C497172:MSH2 protein, human; D000070976:Mismatch Repair Endonuclease PMS2; D000070957:MutL Protein Homolog 1; D051718:MutS Homolog 2 Protein; D045643:DNA Repair Enzymes
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