Body mass index in early adulthood and endometrial cancer risk for mismatch repair gene mutation carriers.

Aung Ko Win James G Dowty Yoland C Antill Dallas R English John A Baron Joanne P Young Graham G Giles Melissa C Southey Ingrid Winship Lara Lipton Susan Parry Stephen N Thibodeau Robert W Haile Steven Gallinger Loïc Le Marchand Noralane M Lindor Polly A Newcomb John L Hopper Mark A Jenkins

Obstet Gynecol

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.

Published: April 2011

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).

Conclusion: 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.

Level Of Evidence: II.

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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3084323	PMC
http://dx.doi.org/10.1097/AOG.0b013e3182110ea3	DOI Listing

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