Endometrial cancer causes
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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]Associate Editor(s)-in-Chief: Monalisa Dmello, M.B,B.S., M.D. [2]
Overview
There are both genetic and environmental causes of endometrial carcinoma. Some of the genetic causes are hereditary nonpolyposis colon cancer (HNPCC) syndrome and cowden syndrome.The sporadic colorectal cancers develop from environmental causes.
Causes
Overall, genetic causes contribute to 2–10% of endometrial cancer cases.[1]
- Lynch syndrome (Hereditary nonpolyposis colon cancer (HNPCC) 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.[2] Ovarian and endometrial cancer develop simultaneously in 20% of people.[3] 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.[4] 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%. 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%.
- 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, compared to the 2–3% risk for unaffected women.[5][6] Cowden syndrome is associated with mutations in PTEN, a tumor suppressor gene, that cause the PTEN protein not to work properly leading to hyperactivity of the mTOR pathway.
References
- ↑ Reinbolt RE, Hays JL (2013). "The Role of PARP Inhibitors in the Treatment of Gynecologic Malignancies". Front Oncol. 3: 237. doi:10.3389/fonc.2013.00237. PMC 3787651. PMID 24098868.
- ↑ Hoffman, Barbara (2012). Williams gynecology. New York: McGraw-Hill Medical. ISBN 9780071716727. Check
|isbn=value: invalid character (help). - ↑ Ma, J; Ledbetter, N; Glenn, L (2013). "Testing women with endometrial cancer for lynch syndrome: should we test all?". Journal of the Advanced Practitioner in Oncology. 4 (5): 322–30. PMC 4093445. PMID 25032011.
- ↑ Hoffman, Barbara (2012). Williams gynecology. New York: McGraw-Hill Medical. ISBN 9780071716727. Check
|isbn=value: invalid character (help). - ↑ Kumar (2009). Robbins and Cotran Pathologic Basis of DiseaseProfessional Edition, 8th ed. Saunders, An Imprint of Elsevier.
- ↑ Cotran, Robbins (2009). Pathologic Basis of Disease. Jacksonville, FL, U.S.A: Saunders//Elsevier. ISBN 978-1-4160-3121-5.