Please use this identifier to cite or link to this item: http://hdl.handle.net/2440/93422
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Type: Journal article
Title: Female hormonal factors and the risk of endometrial cancer in Lynch syndrome
Author: Dashti, S.
Chau, R.
Ouakrim, D.
Buchanan, D.
Clendenning, M.
Young, J.
Winship, I.
Arnold, J.
Ahnen, D.
Haile, R.
Casey, G.
Gallinger, S.
Thibodeau, S.
Lindor, N.
Le Marchand, L.
Newcomb, P.
Potter, J.
Baron, J.
Hopper, J.
Jenkins, M.
et al.
Citation: JAMA, 2015; 314(1):61-71
Publisher: American Medical Association
Issue Date: 2015
ISSN: 0098-7484
1538-3598
Statement of
Responsibility: 
Seyedeh Ghazaleh Dashti, Rowena Chau, Driss Ait Ouakrim, Daniel D. Buchanan, Mark Clendenning, Joanne P. Young, Ingrid M. Winship, Julie Arnold, Dennis J. Ahnen, Robert W. Haile, DrPh, Graham Casey, Steven Gallinger, Stephen N. Thibodeau, Noralane M. Lindor, Loïc Le Marchand, Polly A. Newcomb, John D. Potter, John A. Baron, John L. Hopper, Mark A. Jenkins, Aung Ko Win
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.
Keywords: Colorectal Neoplasms, Hereditary Nonpolyposis; Endometrial Neoplasms; Contraceptives, Oral, Hormonal; Estrogen Replacement Therapy; DNA Mismatch Repair
Rights: © 2015 American Medical Association. All Rights Reserved.
RMID: 0030031903
DOI: 10.1001/jama.2015.6789
Grant ID: http://purl.org/au-research/grants/nhmrc/1042021
http://purl.org/au-research/grants/nhmrc/1074383
Appears in Collections:Medicine publications

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