Hormonal Factors Predict Lynch Syndrome Endometrial Cancer Risk

The risk of endometrial cancer in women with a germline mismatch repair gene mutation is affected by premenopausal hormone-associated factors

medwireNews: Age at menarche, parity and use of hormonal contraception influence the likelihood of endometrial cancer in patients with Lynch syndrome, suggests research published inJAMA.

“These directions and strengths of associations were similar to those for the general population”, say Aung Ko Win, from the University of Melbourne in Victoria, Australia, and co-authors. 

“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.” 

In all, 133 of the 1128 women with a germline mismatch repair gene mutation in the Colon Cancer Family Registry were diagnosed with endometrial cancer, at an incidence of 0.29 cases per 100 person–years. 

Adjusting for a raft of hormone-related factors, the researchers found that women whose first period was at age 13 years or later were significantly less likely to develop endometrial cancer than those with an earlier menarche, with a hazard ratio (HR) of 0.70. 

In addition, one or more live births versus no live births (HR=0.21) and use of a hormonal contraceptive for at least 1 year versus less than this time (HR=0.39) were significantly protective against the development of endometrial cancer. 

“Our results provide further evidence supporting the hypothesis that long-term exposure to hormonal contraceptives may significantly reduce the risk of endometrial cancer in Lynch syndrome”, the researchers comment.

Unlike studies of the general population, the risk of endometrial cancer in Lynch syndrome patients was not significantly associated with age at first or last live birth, or age at menopause.

Nor was risk influenced by use of postmenopausal hormone therapy, even when stratifying by oestrogen-only and oestrogen plus progestin treatments, although the researchers observe that the study was statistically underpowered to detect such an association.

“Because of the small number of women (1%) who reported use of antiestrogen drugs (including tamoxifen and raloxifene), we were unable to investigate associations between these drugs and endometrial cancer risk”, they add.


Dashti SG, Chau R, Ouakrim DA,et al. Female hormonal factors and the risk of endometrial cancer in Lynch syndrome. JAMA 2015; 314: 61–71. doi:10.1001/jama.2015.6789

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