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

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.

• Authors: 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, 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
• Journal: JAMA (JAMA) Vol. 314 Issue 1 Pg. 61-71 (Jul 07 2015) ISSN: 1538-3598 [Electronic] United States
• PMID: 26151267 (Publication Type: Journal Article, Multicenter Study, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)

Chemical References

• Contraceptives, Oral, Hormonal

Topics

• Adolescent
• Adult
• Aged
• Aged, 80 and over
• Colorectal Neoplasms, Hereditary Nonpolyposis (complications, genetics)
• Contraceptives, Oral, Hormonal (pharmacology)
• DNA Mismatch Repair (genetics)
• Endometrial Neoplasms (etiology, prevention & control)
• Estrogen Replacement Therapy
• Female
• Humans
• Maternal Age
• Menarche
• Menopause
• Middle Aged
• Mutation
• Risk
• Young Adult