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Genetics of endometrial cancer

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Abstract

Women who report a history of endometrial cancer in a first-degree relative are at increased risk of endometrial cancer, with a hazard ratio of 1.5 to 2.0. Only a minority of patients with familial endometrial cancer have a recognized cancer syndrome. Lynch syndrome is the most common genetic syndrome associated with endometrial cancer and a marked increased risk of colon cancer. Cowden syndrome is a rare condition resulting from a mutation in the tumor suppressor gene phosphatase and tensin homolog. The risk for endometrial cancer is about five times higher in women with Cowden syndrome than in the general population. Recently, a novel germline mutation in the POLD1 gene that encodes the catalytic subunit of DNA polymerase δ was described in several families with multiple cases of endometrial cancer. This mutation is also associated with colorectal cancer. The association between BRCA1 mutations and endometrial cancer has been investigated in several studies; it appears that the risk of endometrial cancer is restricted to women with a history of tamoxifen exposure. In recent years, research has focused on genetic polymorphisms that are associated with endometrial cancer risk. Although many polymorphisms have been identified, their clinical significance is unclear and they have not been adapted for clinical practice.

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The authors declare that they have no conflict of interest.

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Authors and Affiliations

  1. Department of Oncology, Lin and Carmel Medical Centers, 7 Michal St., 34362, Haifa, Israel

    Ayelet Shai

  2. Women’s College Research Institute, Familial Breast Cancer Research Unit, 790 Bay Street, 7th Floor, Toronto, ON, M5G 1N8, Canada

    Yakir Segev & Steven A. Narod

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  1. Ayelet Shai
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  2. Yakir Segev
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Shai, A., Segev, Y. & Narod, S.A. Genetics of endometrial cancer. Familial Cancer 13, 499–505 (2014). https://doi.org/10.1007/s10689-014-9722-7

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