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 PARTICIPANTSA 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). Later age at menarche, parity (Ն1 live births), and hormonal contraceptive use (Ն1 year) were associated with a lower risk of endometrial cancer. No. (%) of Women Incidence Hazard Ratio (95% CI) With Available Data Diagnosed With Endometrial Cancer Incidence per 100 Person-Years Difference (95% CI) Age at menarche ≥13 Years 639 70 (11) 0.27 −0.04 (−0.15 to 0.05) 0.70 (0.44 to 1.11) <13 Years (reference) 454 57 (12.6) 0.31 Risk per year 0.85 (0.73 to 0.99) Parity ≥1 Live births 815 88 (10.8) 0.25 −0.18 (−0.32 to −0.04) 0.21 (0.10 to 0.42) Nulliparous (reference) 278 40 (14.4) 0.43 Hormonal contraceptive use ≥1 Year 803 70 (8.7) 0.22 −0.23 (−0.36 to −0.11) 0.39 (0.23 to 0.64) <1 Year (reference) 297 57 (19.2) 0.45 Risk per year 0.93 (0.89 to 0.97)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 RELEVANCEFor 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.

Comparison of lifestyle, hormonal and medical factors in women with sporadic and Lynch syndrome-associated endometrial cancer: A retrospective case-case study

“…No significant effect of contraceptive use on the ECC risk was detected among MLH1 mutation carriers in the study of Blokhuis et al (13), although that study included only 12 cases of EC in 87 mutation-positive females, in comparison with 121 mutation-negative female relatives. However, the previously described large retrospective cohort study revealed a marked EC risk reduction among LS mutation carriers with a history of contraceptive use extending to 1 year (19). The results of the present study, demonstrating fewer spontaneous and induced abortions among mutation carriers, may also be interpreted as more premeditated family planning being carried out for the LS mutation carriers tested at a fertile age, and this warrants further investigation.…”

“…According to these studies, risk factors are partially shared in sporadic and hereditary EC, since the BMI appeared not to have an effect on EC risk, although parity, longer use of hormonal contraceptives and a later age at menarche reduced the risk of EC in LS women (19,20). It has been suggested that LS women have more non-endometrioid tumors compared with sporadic patients, which could at least partly explain certain of the differences in the reported risk factor profiles (19)(20)(21). LS mutation carriers in the present study used hormonal contraceptives more frequently than non-carriers.…”

“…This may reflect EC risk-reducing strategies recommended for mutation carriers, or improved standards of advisory family planning. Only a few studies have previously addressed the influence of contraceptive use on ECC risk among LS women (13,19). No significant effect of contraceptive use on the ECC risk was detected among MLH1 mutation carriers in the study of Blokhuis et al (13), although that study included only 12 cases of EC in 87 mutation-positive females, in comparison with 121 mutation-negative female relatives.…”

“…To date, only two comprehensive retrospective cohort studies of verified LS populations have been published with regard to EC risk (19,20). According to these studies, risk factors are partially shared in sporadic and hereditary EC, since the BMI appeared not to have an effect on EC risk, although parity, longer use of hormonal contraceptives and a later age at menarche reduced the risk of EC in LS women (19,20).…”

The impact of metabolic syndrome on the clinical profile and tumor characteristics of endometrial carcinoma

“…Dashti SG et al found that 7.5% of endometrial cancer patients had normal BMI 2 years before diagnosis compared to 29.6% among the control group. 18 They reported that overweight was reported in 1.5% and obese in 6.8% of the endometrial cancer patients.…”