Endometrial cancer risk factors

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]

Overview

Common risk factors in the development of endometrial cancer are estrogen exposure, tamoxifen use, obesity, diabetes, high blood pressure and genetic disorders.

Risk Factors

Some of the risk factors for endometrial cancer are:

1. Estrogen exposure
  • Women who have received higher doses or longer periods of estrogen therapy have higher risks of endometrial cancer.[1]
2. Early menarche
  • Women who have menstrual periods at an early age also increases the number of years the body is exposed to estrogen and increases a woman's risk of endometrial cancer.
3.Early menopause
  • Women who reach menopause at an older age are exposed to estrogen for a longer time and have an increased risk of endometrial cancer.
4. Nulliparity
  • Never being pregnant is also a risk factor for endometrial cancer. Because estrogen levels are lower during pregnancy, women who have never been pregnant are exposed to estrogen for a longer time than women who have been pregnant. This increases the risk of endometrial cancer.[2]
5. Tamoxifen
  • Tamoxifen is one of a group of drugs called selective estrogen receptor modulators, or SERMs. Tamoxifen is used to prevent breast cancer in women who are at high risk for the disease, but it increases the risk of endometrial cancer. This risk is greater in postmenopausal women.[3]
6. Genetic disorders
  • Hereditary nonpolyposis colon cancer (HNPCC) syndrome (Lynch syndrome): Women with Lynch syndrome have a 40–60% risk of developing endometrial cancer, higher than their risk of developing colorectal (bowel) or ovarian cancer.[4] 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.[5] Other genes mutated in Lynch syndrome include MSH2, MSH6, and PMS2, which are also mismatch repair genes.
  • Cowden syndrome: Women with Cowden syndrome have a 5–10% lifetime risk of developing endometrial cancer, compared to the 2–3% risk for unaffected women.[6][7] 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.
7. Polycystic ovary syndrome
  • Women who have polycystic ovary syndrome have an increased risk of endometrial cancer.
8. Body fat
  • Obesity increases the risk of endometrial cancer. This may be because obesity is related to other risk factors such as estrogen levels, polycystic ovary syndrome, lack of physical activity, and a diet that is high in saturated fats.[8]
9. High blood pressure
10. Prior pelvic radiation therapy
  • Prior pelvic radiation therapy can increase the risk of endometrial cancer by damaging the DNA of cells.
11. Diabetes
  • Diabetes epidemiological data shows that endometrial cancer may be as much as four times more common in women with diabetes.
12. Ovarian tumors
  • The granulosa-theca cell tumor, one type of ovarian tumor, can produce estrogen and increase the risk of endometrial cancer.

References

  1. Vern L. Katz, Gretchen M. Lentz (2012). Comprehensive gynecology. Philadelphia, PA, USA: Elsevier/ Mosby. ISBN 978-0-323-06986-1.
  2. Vale CL, Tierney J, Bull SJ, Symonds PR (2012). "Chemotherapy for advanced, recurrent or metastatic endometrial carcinoma". Cochrane Database Syst Rev. 8: CD003915. doi:10.1002/14651858.CD003915.pub4. PMID 22895938.
  3. Staley H, McCallum I, Bruce J (2012). "Postoperative tamoxifen for ductal carcinoma in situ". Cochrane Database Syst Rev. 10: CD007847. doi:10.1002/14651858.CD007847.pub2. PMID 23076938.
  4. Hoffman, Barbara (2012). Williams gynecology. New York: McGraw-Hill Medical. ISBN 9780071716727. Check |isbn= value: invalid character (help).
  5. Hoffman, Barbara (2012). Williams gynecology. New York: McGraw-Hill Medical. ISBN 9780071716727. Check |isbn= value: invalid character (help).
  6. Kumar (2009). Robbins and Cotran Pathologic Basis of DiseaseProfessional Edition, 8th ed. Saunders, An Imprint of Elsevier.
  7. Cotran, Robbins (2009). Pathologic Basis of Disease. Jacksonville, FL, U.S.A: Saunders//Elsevier. ISBN 978-1-4160-3121-5.
  8. SGO Clinical Practice Endometrial Cancer Working Group. Burke WM, Orr J, Leitao M, Salom E, Gehrig P; et al. (2014). "Endometrial cancer: a review and current management strategies: part I." Gynecol Oncol. 134 (2): 385–92. doi:10.1016/j.ygyno.2014.05.018. PMID 24905773.


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