Body Mass Index in Early Adulthood and Endometrial Cancer Risk for Mismatch Repair Gene Mutation Carriers
1 Centre for Molecular, Environmental, Genetic and Analytic Epidemiology, The University of Melbourne, Parkville, Victoria, Australia
2 Familial Cancer Centre, Southern Health, Victoria, Australia
3 Cancer Epidemiology Centre, Cancer Council Victoria, Australia
4 Department of Medicine and Department of Community and Family Medicine, Dartmouth Medical School, Lebanon, New Hampshire, USA
5 Familial Cancer Laboratory, Queensland Institute of Medical Research, Australia
6 Department of Medicine, University of Queensland, Brisbane, Queensland, Australia
7 Genetic Epidemiology Laboratory, Department of Pathology, The University of Melbourne, Parkville, Victoria, Australia
8 Adult Clinical Genetics, The University of Melbourne, Victoria, Australia
9 Ludwig Institute for Cancer Research, The Royal Melbourne Hospital, Parkville, Victoria, Australia
10 New Zealand Familial Gastrointestinal Cancer Registry, Auckland Hospital, New Zealand
11 Department of Gastroenterology, Middlemore Hospital, Auckland, New Zealand
12 Department of Medical Genetics, Mayo Clinic, Rochester, Minnesota, USA
13 Department of Preventive Medicine, University of Southern California, Los Angeles, California, USA
14 Cancer Care Ontario, Toronto, Ontario, Canada
15 Samuel Lunenfeld Research Institute, Mount Sinai Hospital, Toronto, Ontario, Canada
16 Cancer Research Center of Hawaii, University of Hawaii, Honolulu, Hawaii, USA
17 Cancer Prevention Program, Fred Hutchinson Cancer Research Center, Seattle, Washington, USA
The study comprised: 601 female carriers of a MMR gene mutation (245 in MLH1, 299 in MSH2, 38 in MSH6, and 19 in PMS2) from 286 families contributing 26,027 person-years, of which 126 (21%) were diagnosed with endometrial cancer (incidence 4.84 (95% CI 4.07–5.76) per 1,000 person-years); and 533 female non-carriers from 182 families contributing 25,666 person-years, of which 8 (2%) were diagnosed with endometrial cancer (incidence 0.31 (95% CI 0.16–0.62) per 1,000 person-years). Of all carriers, 847 (75%) were recruited in Australia or New Zealand, 191 (17%) in the USA and 96 (8%) in Canada. Baseline characteristics of the study subjects are summarized in . The mean age at diagnosis of endometrial cancer was 47.6 (standard deviation (SD) 8.2) years for carriers and 44.5 (SD 9.9) years for non-carriers. The mean BMI at age 20 years was 21.8 (SD 3.7) kg/m2 for carriers and 21.8 (SD 4.0) kg/m2 for non-carriers. There was no statistical evidence for the mean BMI, nor the distribution of mutated MMR gene to differ by country or ascertainment source (data not shown).
Baseline characteristics of study subjects by mismatch repair mutation status
shows no statistically significant evidence for an association between BMI and endometrial cancer risk for carriers of mutations when all carriers of MMR gene mutation are combined (HR 0.73 per 5 kg/m2; 95% CI 0.40–1.34; P = 0.31) after adjusting for age at menarche, year of birth, hormonal contraceptive use and cigarette smoking at age 20 and specific MMR gene mutated. presents associations for BMI and endometrial cancer risk separately for carriers of mutations in each MMR gene.
Hazard ratios (HR) for association between body mass index (BMI) at age 20 years and endometrial cancer risk for mismatch repair gene mutation carriers and noncarriers.
Hazard ratios for association between body mass index (BMI, per 5 kg/m2) at age 20 years and endometrial cancer risk by mutated mismatch repair gene.
For non-carriers, endometrial cancer risk was estimated to increase by 74% for each increase of 5 kg/m2 in BMI (HR 1.74; 95% CI 1.27–2.37; P <0.001) after adjusting for age at menarche, year of birth, hormonal contraceptive use and cigarette smoking at age 20. The HR for non-carriers was greater than that for carriers (interaction between mutation carrier status and BMI; P = 0.04).
There was no evidence for a non-linear association between (log) BMI (as a continuous variable) and the hazards for endometrial cancer for either carriers or non-carrier (P = 0.90).