Endometrial cancer causes
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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]
Overview
The cause of endometrial cancer has not been identified.
Overview
There are both genetic and environmental causes of endometrial carcinoma. Some of the genetic causes are Hereditary nonpolyposis colon cancer (HNPCC) syndrome.The sporadic colorectal cancers develop from environmental causes.
Causes
Overall, genetic causes contribute to 2–10% of endometrial cancer cases.
- Lynch syndrome
Lynch syndrome, an autosomal dominant genetic disorder that mainly causes colorectal cancer, also causes endometrial cancer, especially before menopause. Women with Lynch syndrome have a 40–60% risk of developing endometrial cancer, higher than their risk of developing colorectal (bowel) or ovarian cancer.[1] Ovarian and endometrial cancer develop simultaneously in 20% of people. Endometrial cancer nearly always develops before colon cancer, on average, 11 years before.[2] Carcinogenesis in Lynch syndrome comes from a mutation in MLH1 and/or MLH2: genes that participate in the process of mismatch repair, which allows a cell to correct mistakes in the DNA.[1] Other genes mutated in Lynch syndrome include MSH2, MSH6, and PMS2, which are also mismatch repair genes. Women with Lynch syndrome represent 2–3% of endometrial cancer cases; some sources place this as high as 5%.[2][3] Depending on the gene mutation, women with Lynch syndrome have different risks of endometrial cancer. With MLH1 mutations, the risk is 54%; with MSH2, 21%; and with MSH6, 16%.[4]
- Cowden syndrome
Women with a family history of endometrial cancer are at higher risk. The inherited genetic condition Cowden syndrome can also cause endometrial cancer. Women with this disorder have a 5–10% lifetime risk of developing endometrial cancer,[5] compared to the 2–3% risk for unaffected women.[2]