title: Body mass index in early adulthood and endometrial cancer risk for mismatch repair gene mutation carriers.
abstract: OBJECTIVE
  To investigate the association of body mass index (BMI) in early adulthood and endometrial cancer risk for carriers of a germline mutation in a DNA mismatch repair gene.
  
  
  METHODS
  We estimated the association between BMI at age 18-20 years and endometrial cancer risk for mismatch repair gene mutation carriers and, as a comparison group, noncarriers using 601 female carriers of a germline mutation in a mismatch repair gene (245 MLH1, 299 MSH2, 38 MSH6, and 19 PMS2) and 533 female noncarriers from the Colon Cancer Family Registry using a weighted Cox proportional hazards regression.
  
  
  RESULTS
  During 51,693 person-years of observation, we observed diagnoses of endometrial cancer for 126 carriers and eight noncarriers. For carriers, there was no evidence of an association between BMI at age 20 years and endometrial cancer (adjusted hazard ratio 0.73 per 5 kg/m²; 95% confidence interval [CI], 0.40-1.34; P=.31). For noncarriers, endometrial cancer risk increased by 74% for each 5-kg/m² increment in BMI (adjusted hazard ratio 1.74; 95% CI 1.27-2.37; P<.001). The hazard ratio for BMI and endometrial cancer for noncarriers was greater than for carriers (P=.04).
  
  
  CONCLUSIONS
  The effect of body mass on endometrial cancer risk depends on the woman's mismatch repair gene mutation carrier status, suggesting obesity-independent endometrial carcinogenesis for carriers.
  
  
  METHODS
  II.
authors.affiliation: From the Centre for Molecular, Environmental, Genetic and Analytic Epidemiology, The University of Melbourne, Parkville, Victoria, Australia; the Familial Cancer Centre, Southern Health, Victoria, Australia; the Cancer Epidemiology Centre, Cancer Council Victoria, Victoria, Australia; the Department of Medicine and Department of Community and Family Medicine, Dartmouth Medical School, Lebanon, New Hampshire; the Familial Cancer Laboratory, Queensland Institute of Medical Research, Queensland, Australia; the Department of Medicine, University of Queensland, Brisbane, Queensland, Australia; the Genetic Epidemiology Laboratory, Department of Pathology, The University of Melbourne, Parkville, Victoria, Australia; Adult Clinical Genetics, The University of Melbourne, Victoria, Australia; Ludwig Institute for Cancer Research, The Royal Melbourne Hospital, Parkville, Victoria, Australia; New Zealand Familial Gastrointestinal Cancer Registry, Auckland Hospital, Auckland, New Zealand; the Department of Gastroenterology, Middlemore Hospital, Auckland, New Zealand; the Department of Medical Genetics, Mayo Clinic, Rochester, Minnesota; the Department of Preventive Medicine, University of Southern California, Los Angeles, California; Cancer Care Ontario, Toronto, Ontario, Canada; the Samuel Lunenfeld Research Institute, Mount Sinai Hospital, Toronto, Ontario, Canada; the Cancer Research Center of Hawaii, University of Hawaii, Honolulu, Hawaii; and the Cancer Prevention Program, Fred Hutchinson Cancer Research Center, Seattle, Washington.
authors.forename: Aung Ko
authors.initials: AK
authors.lastname: Win
authors.forename: James G
authors.initials: JG
authors.lastname: Dowty
authors.forename: Yoland C
authors.initials: YC
authors.lastname: Antill
authors.forename: Dallas R
authors.initials: DR
authors.lastname: English
authors.forename: John A
authors.initials: JA
authors.lastname: Baron
authors.forename: Joanne P
authors.initials: JP
authors.lastname: Young
authors.forename: Graham G
authors.initials: GG
authors.lastname: Giles
authors.forename: Melissa C
authors.initials: MC
authors.lastname: Southey
authors.forename: Ingrid
authors.initials: I
authors.lastname: Winship
authors.forename: Lara
authors.initials: L
authors.lastname: Lipton
authors.forename: Susan
authors.initials: S
authors.lastname: Parry
authors.forename: Stephen N
authors.initials: SN
authors.lastname: Thibodeau
authors.forename: Robert W
authors.initials: RW
authors.lastname: Haile
authors.forename: Steven
authors.initials: S
authors.lastname: Gallinger
authors.forename: Loïc
authors.initials: L
authors.lastname: Le Marchand
authors.forename: Noralane M
authors.initials: NM
authors.lastname: Lindor
authors.forename: Polly A
authors.initials: PA
authors.lastname: Newcomb
authors.forename: John L
authors.initials: JL
authors.lastname: Hopper
authors.forename: Mark A
authors.initials: MA
authors.lastname: Jenkins
mesh_terms: D000251:Adenosine Triphosphatases / Q000235:genetics*; D000293:Adolescent; D000367:Age Factors; D015992:Body Mass Index; D015331:Cohort Studies; D016001:Confidence Intervals; 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* / Q000503:physiopathology; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D020022:Genetic Predisposition to Disease / Q000453:epidemiology*; D018095:Germ-Line Mutation; D006579:Heterozygote; D006801:Humans; D015994:Incidence; D000070976:Mismatch Repair Endonuclease PMS2; D011379:Prognosis; D012016:Reference Values; D018570:Risk Assessment; D014739:Victoria; D055815:Young Adult
chemical_list: D004268:DNA-Binding Proteins; D000251:Adenosine Triphosphatases; C094934:PMS2 protein, human; D000070976:Mismatch Repair Endonuclease PMS2; D045643:DNA Repair Enzymes