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Original Investigation
July 7, 2015

Female Hormonal Factors and the Risk of Endometrial Cancer in Lynch Syndrome

Author Affiliations
  • 1Centre for Epidemiology and Biostatistics, Melbourne School of Population and Global Health, The University of Melbourne, Parkville, Victoria, Australia
  • 2Oncogenomics Group, Genetic Epidemiology Laboratory, Department of Pathology, The University of Melbourne
  • 3Departments of Haematology and Oncology, The Queen Elizabeth Hospital, Woodville, South Australia, Australia
  • 4SAHMRI Colorectal Node, Basil Hetzel Institute for Translational Research, Woodville, South Australia
  • 5School of Medicine, University of Adelaide, South Australia
  • 6Department of Medicine, The University of Melbourne
  • 7Genetic Medicine, The Royal Melbourne Hospital, Parkville, Victoria, Australia
  • 8New Zealand Familial Gastrointestinal Cancer Service, Auckland, New Zealand
  • 9Department of Medicine, University of Colorado School of Medicine, Denver
  • 10Division of Oncology, Department of Medicine, Stanford Cancer Institute, Stanford University, Stanford, California
  • 11Department of Preventive Medicine, Keck School of Medicine and Norris Comprehensive Cancer Center, University of Southern California, Los Angeles
  • 12Lunenfeld Tanenbaum Research Institute, Mount Sinai Hospital, University of Toronto, Toronto, Ontario, Canada
  • 13Molecular Genetics Laboratory, Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, Minnesota
  • 14Department of Health Science Research, Mayo Clinic Arizona, Scottsdale
  • 15University of Hawaii Cancer Center, Honolulu
  • 16Public Health Sciences Division, Fred Hutchinson Cancer Research Center, Seattle, Washington
  • 17School of Public Health, University of Washington, Seattle
  • 18Centre for Public Health Research, Massey University, Wellington, New Zealand
  • 19Department of Medicine, University of North Carolina, Chapel Hill
  • 20Department of Epidemiology and Institute of Health and Environment, School of Public Health, Seoul National University, Seoul, Korea
JAMA. 2015;314(1):61-71. doi:10.1001/jama.2015.6789

Importance  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.

Design, Setting, and Participants  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.

Exposures  Age at menarche, first and last live birth, and menopause; number of live births; hormonal contraceptive use; and postmenopausal hormone use.

Main Outcomes and Measures  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 and Relevance  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.