Seyedeh Ghazaleh Dashti1, Rowena Chau1, Driss Ait Ouakrim1, Daniel D Buchanan2, Mark Clendenning3, Joanne P Young4, Ingrid M Winship5, Julie Arnold6, Dennis J Ahnen7, Robert W Haile8, Graham Casey9, Steven Gallinger10, Stephen N Thibodeau11, Noralane M Lindor12, Loïc Le Marchand13, Polly A Newcomb14, John D Potter15, John A Baron16, John L Hopper17, Mark A Jenkins1, Aung Ko Win1. 1. Centre for Epidemiology and Biostatistics, Melbourne School of Population and Global Health, The University of Melbourne, Parkville, Victoria, Australia. 2. 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. 3. Oncogenomics Group, Genetic Epidemiology Laboratory, Department of Pathology, The University of Melbourne. 4. 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. 5. Department of Medicine, The University of Melbourne7Genetic Medicine, The Royal Melbourne Hospital, Parkville, Victoria, Australia. 6. New Zealand Familial Gastrointestinal Cancer Service, Auckland, New Zealand. 7. Department of Medicine, University of Colorado School of Medicine, Denver. 8. Division of Oncology, Department of Medicine, Stanford Cancer Institute, Stanford University, Stanford, California. 9. Department of Preventive Medicine, Keck School of Medicine and Norris Comprehensive Cancer Center, University of Southern California, Los Angeles. 10. Lunenfeld Tanenbaum Research Institute, Mount Sinai Hospital, University of Toronto, Toronto, Ontario, Canada. 11. Molecular Genetics Laboratory, Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, Minnesota. 12. Department of Health Science Research, Mayo Clinic Arizona, Scottsdale. 13. University of Hawaii Cancer Center, Honolulu. 14. Public Health Sciences Division, Fred Hutchinson Cancer Research Center, Seattle, Washington17School of Public Health, University of Washington, Seattle. 15. 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. 16. Department of Medicine, University of North Carolina, Chapel Hill. 17. 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.
Abstract
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.
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.
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