title: Female Hormonal Factors and the Risk of Endometrial Cancer in Lynch Syndrome.
abstract: OBJECTIVE
  Apart from hysterectomy, there is no consensus recommendation for reducing endometrial cancer risk for women with a mismatch repair gene mutation (Lynch syndrome).
  
  
  OBJECTIVE
  To investigate the association between hormonal factors and endometrial cancer risk in Lynch syndrome.
  
  
  METHODS
  A retrospective cohort study included 1128 women with a mismatch repair gene mutation identified from the Colon Cancer Family Registry. Data were analyzed with a weighted cohort approach. Participants were recruited between 1997 and 2012 from centers across the United States, Australia, Canada, and New Zealand.
  
  
  METHODS
  Age at menarche, first and last live birth, and menopause; number of live births; hormonal contraceptive use; and postmenopausal hormone use.
  
  
  METHODS
  Self-reported diagnosis of endometrial cancer.
  
  
  RESULTS
  Endometrial cancer was diagnosed in 133 women (incidence rate per 100 person-years, 0.29; 95% CI, 0.24 to 0.34). Endometrial cancer was diagnosed in 11% (n = 70) of women with age at menarche greater than or equal to 13 years compared with 12.6% (n = 57) of women with age at menarche less than 13 years (incidence rate per 100 person-years, 0.27 vs 0.31; rate difference, -0.04 [95% CI, -0.15 to 0.05]; hazard ratio per year, 0.85 [95% CI, 0.73 to 0.99]; P = .04). Endometrial cancer was diagnosed in 10.8% (n = 88) of parous women compared with 14.4% (n = 40) of nulliparous women (incidence rate per 100 person-years, 0.25 vs 0.43; rate difference, -0.18 [95% CI, -0.32 to -0.04]; hazard ratio, 0.21 [95% CI, 0.10 to 0.42]; P < .001). Endometrial cancer was diagnosed in 8.7% (n = 70) of women who used hormonal contraceptives greater than or equal to 1 year compared with 19.2% (n = 57) of women who used contraceptives less than 1 year (incidence rate per 100 person-years, 0.22 vs 0.45; rate difference, -0.23 [95% CI, -0.36 to -0.11]; hazard ratio, 0.39 [95% CI, 0.23 to 0.64]; P < .001). There was no statistically significant association between endometrial cancer and age at first and last live birth, age at menopause, and postmenopausal hormone use.
  
  
  CONCLUSIONS
  For women with a mismatch repair gene mutation, some endogenous and exogenous hormonal factors were associated with a lower risk of endometrial cancer. These directions and strengths of associations were similar to those for the general population. If replicated, these findings suggest that women with a mismatch repair gene mutation may be counseled like the general population in regard to hormonal influences on endometrial cancer risk.
authors.affiliation: Centre for Epidemiology and Biostatistics, Melbourne School of Population and Global Health, The University of Melbourne, Parkville, Victoria, Australia.
authors.forename: Seyedeh Ghazaleh
authors.initials: SG
authors.lastname: Dashti
authors.affiliation: Centre for Epidemiology and Biostatistics, Melbourne School of Population and Global Health, The University of Melbourne, Parkville, Victoria, Australia.
authors.forename: Rowena
authors.initials: R
authors.lastname: Chau
authors.affiliation: Centre for Epidemiology and Biostatistics, Melbourne School of Population and Global Health, The University of Melbourne, Parkville, Victoria, Australia.
authors.forename: Driss Ait
authors.initials: DA
authors.lastname: Ouakrim
authors.affiliation: Centre for Epidemiology and Biostatistics, Melbourne School of Population and Global Health, The University of Melbourne, Parkville, Victoria, Australia2Oncogenomics Group, Genetic Epidemiology Laboratory, Department of Pathology, The University of Melbou.
authors.forename: Daniel D
authors.initials: DD
authors.lastname: Buchanan
authors.affiliation: Oncogenomics Group, Genetic Epidemiology Laboratory, Department of Pathology, The University of Melbourne.
authors.forename: Mark
authors.initials: M
authors.lastname: Clendenning
authors.affiliation: Departments of Haematology and Oncology, The Queen Elizabeth Hospital, Woodville, South Australia, Australia4SAHMRI Colorectal Node, Basil Hetzel Institute for Translational Research, Woodville, South Australia5School of Medicine, University of Adelaide.
authors.forename: Joanne P
authors.initials: JP
authors.lastname: Young
authors.affiliation: Department of Medicine, The University of Melbourne7Genetic Medicine, The Royal Melbourne Hospital, Parkville, Victoria, Australia.
authors.forename: Ingrid M
authors.initials: IM
authors.lastname: Winship
authors.affiliation: New Zealand Familial Gastrointestinal Cancer Service, Auckland, New Zealand.
authors.forename: Julie
authors.initials: J
authors.lastname: Arnold
authors.affiliation: Department of Medicine, University of Colorado School of Medicine, Denver.
authors.forename: Dennis J
authors.initials: DJ
authors.lastname: Ahnen
authors.affiliation: Division of Oncology, Department of Medicine, Stanford Cancer Institute, Stanford University, Stanford, California.
authors.forename: Robert W
authors.initials: RW
authors.lastname: Haile
authors.affiliation: Department of Preventive Medicine, Keck School of Medicine and Norris Comprehensive Cancer Center, University of Southern California, Los Angeles.
authors.forename: Graham
authors.initials: G
authors.lastname: Casey
authors.affiliation: Lunenfeld Tanenbaum Research Institute, Mount Sinai Hospital, University of Toronto, Toronto, Ontario, Canada.
authors.forename: Steven
authors.initials: S
authors.lastname: Gallinger
authors.affiliation: Molecular Genetics Laboratory, Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, Minnesota.
authors.forename: Stephen N
authors.initials: SN
authors.lastname: Thibodeau
authors.affiliation: Department of Health Science Research, Mayo Clinic Arizona, Scottsdale.
authors.forename: Noralane M
authors.initials: NM
authors.lastname: Lindor
authors.affiliation: University of Hawaii Cancer Center, Honolulu.
authors.forename: Loïc
authors.initials: L
authors.lastname: Le Marchand
authors.affiliation: Public Health Sciences Division, Fred Hutchinson Cancer Research Center, Seattle, Washington17School of Public Health, University of Washington, Seattle.
authors.forename: Polly A
authors.initials: PA
authors.lastname: Newcomb
authors.affiliation: Public Health Sciences Division, Fred Hutchinson Cancer Research Center, Seattle, Washington17School of Public Health, University of Washington, Seattle18Centre for Public Health Research, Massey University, Wellington, New Zealand.
authors.forename: John D
authors.initials: JD
authors.lastname: Potter
authors.affiliation: Department of Medicine, University of North Carolina, Chapel Hill.
authors.forename: John A
authors.initials: JA
authors.lastname: Baron
authors.affiliation: Centre for Epidemiology and Biostatistics, Melbourne School of Population and Global Health, The University of Melbourne, Parkville, Victoria, Australia20Department of Epidemiology and Institute of Health and Environment, School of Public Health, Seoul Na.
authors.forename: John L
authors.initials: JL
authors.lastname: Hopper
authors.affiliation: Centre for Epidemiology and Biostatistics, Melbourne School of Population and Global Health, The University of Melbourne, Parkville, Victoria, Australia.
authors.forename: Mark A
authors.initials: MA
authors.lastname: Jenkins
authors.affiliation: Centre for Epidemiology and Biostatistics, Melbourne School of Population and Global Health, The University of Melbourne, Parkville, Victoria, Australia.
authors.forename: Aung Ko
authors.initials: AK
authors.lastname: Win
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D003123:Colorectal Neoplasms, Hereditary Nonpolyposis / Q000150:complications* / Q000235:genetics; D003278:Contraceptives, Oral, Hormonal / Q000494:pharmacology*; D053843:DNA Mismatch Repair / Q000235:genetics*; D016889:Endometrial Neoplasms / Q000209:etiology* / Q000517:prevention & control; D015914:Estrogen Replacement Therapy; D005260:Female; D006801:Humans; D008423:Maternal Age; D008572:Menarche; D008593:Menopause; D008875:Middle Aged; D009154:Mutation; D012306:Risk; D055815:Young Adult
chemical_list: D003278:Contraceptives, Oral, Hormonal