Familial Cancer

, Volume 12, Issue 2, pp 273–277

Endometrial and ovarian cancer in women with Lynch syndrome: update in screening and prevention

Original Article

Abstract

Women with Lynch syndrome have an additional need to address the substantial increased lifetime risk of endometrial and ovarian cancer. Endometrial or ovarian cancer can be the presenting cancer in individuals with Lynch syndrome, or can be a second cancer. Lifetime risk of endometrial cancer in women with MLH1 or MSH2 mutations is approximately 40 %, with a median age of 49. Women with MSH6 mutations have a similar risk of endometrial cancer but a later age of diagnosis. Lynch syndrome-associated endometrial cancers are primarily endometrioid, although non-endometrioid subtypes including clear cell, papillary serous and MMMT have been reported. In addition, endometrial cancers arising in the lower uterine segment, while rare in the general population, are enriched in women with Lynch syndrome. Ovarian cancer risk in women with Lynch syndrome is 6–8 %, and Lynch syndrome-associated ovarian cancers exhibit a variety of histopathological subtypes. Studies of endometrial cancer screening in Lynch syndrome have been small, and more recently have focused on the use of office endometrial biopsy to identify pre-malignant and early stage cancers. Prevention options include the use of oral contraceptives, which are known to be highly effective for decreasing risk of both endometrial and ovarian cancer in the general population, and prophylactic surgery to remove the uterus and ovaries.

Keywords

Cancer prevention Cancer screening Endometrial cancer Lynch syndrome Ovarian cancer 

References

  1. 1.
    Lu K et al (2004) Gynecological malignancy as a “sentinel cancer” for women with HNPCC. Gynecol Oncol 92:421Google Scholar
  2. 2.
    Bonadona V, Bonaiti B, Olschwang S et al (2011) Cancer risks associated with germline mutations in MLH1, MSH2, and MSH6 genes in Lynch syndrome. JAMA J Am Med Assoc 305:2304–2310CrossRefGoogle Scholar
  3. 3.
    Stoffel E, Mukherjee B, Raymond VM et al (2009) Calculation of risk of colorectal and endometrial cancer among patients with Lynch syndrome. Gastroenterology 137:1621–1627PubMedCrossRefGoogle Scholar
  4. 4.
    Baglietto L, Lindor NM, Dowty JG et al (2010) Risks of Lynch syndrome cancers for MSH6 mutation carriers. J Natl Cancer Inst 102:193–201PubMedCrossRefGoogle Scholar
  5. 5.
    Senter L, Clendenning M, Sotamaa K et al (2008) The clinical phenotype of Lynch syndrome due to germ-line PMS2 mutations. Gastroenterology 135:419–428PubMedCrossRefGoogle Scholar
  6. 6.
    Kempers MJ, Kuiper RP, Ockeloen CW et al (2011) Risk of colorectal and endometrial cancers in EPCAM deletion-positive Lynch syndrome: a cohort study. Lancet Oncol 12:49–55PubMedCrossRefGoogle Scholar
  7. 7.
    Lynch HT, Riegert-Johnson DL, Snyder C et al (2011) Lynch syndrome-associated extracolonic tumors are rare in two extended families with the same EPCAM deletion. Am J Gastroenterol 106:1829–1836PubMedCrossRefGoogle Scholar
  8. 8.
    Broaddus RR, Lynch HT, Chen LM et al (2006) Pathologic features of endometrial carcinoma associated with HNPCC: a comparison with sporadic endometrial carcinoma. Cancer 106:87–94PubMedCrossRefGoogle Scholar
  9. 9.
    Westin SN, Lacour RA, Urbauer DL et al (2008) Carcinoma of the lower uterine segment: a newly described association with Lynch syndrome. J Clin Oncol 26:5965–5971PubMedCrossRefGoogle Scholar
  10. 10.
    Engel C, Loeffler M, Steinke V et al (2012) Risks of less common cancers in proven mutation carriers with lynch syndrome. J Clin Oncol Off J Am Soc Clin Oncol 30:4409–4415CrossRefGoogle Scholar
  11. 11.
    Watson P, Vasen HF, Mecklin JP et al (2008) The risk of extra-colonic, extra-endometrial cancer in the Lynch syndrome. Int J Cancer 123:444–449PubMedCrossRefGoogle Scholar
  12. 12.
    Ketabi Z, Bartuma K, Bernstein I et al (2011) Ovarian cancer linked to Lynch syndrome typically presents as early-onset, non-serous epithelial tumors. Gynecol Oncol 121:462–465PubMedCrossRefGoogle Scholar
  13. 13.
    Watson P, Butzow R, Lynch HT et al (2001) The clinical features of ovarian cancer in hereditary nonpolyposis colorectal cancer. Gynecol Oncol 82:223–228PubMedCrossRefGoogle Scholar
  14. 14.
    Dove-Edwin I, Boks D, Goff S et al (2002) The outcome of endometrial carcinoma surveillance by ultrasound scan in women at risk of hereditary nonpolyposis colorectal carcinoma and familial colorectal carcinoma. Cancer 94:1708–1712PubMedCrossRefGoogle Scholar
  15. 15.
    Rijcken FE, Mourits MJ, Kleibeuker JH, Hollema H, van der Zee AG (2003) Gynecologic screening in hereditary nonpolyposis colorectal cancer. Gynecol Oncol 91:74–80PubMedCrossRefGoogle Scholar
  16. 16.
    Renkonen-Sinisalo L, Butzow R, Leminen A, Lehtovirta P, Mecklin JP, Jarvinen HJ (2007) Surveillance for endometrial cancer in hereditary nonpolyposis colorectal cancer syndrome. Int J Cancer 120:821–824PubMedCrossRefGoogle Scholar
  17. 17.
    Jarvinen HJ, Renkonen-Sinisalo L, Aktan-Collan K, Peltomaki P, Aaltonen LA, Mecklin JP (2009) Ten years after mutation testing for Lynch syndrome: cancer incidence and outcome in mutation-positive and mutation-negative family members. J Clin Oncol 27:4793–4797PubMedCrossRefGoogle Scholar
  18. 18.
    Manchanda R, Saridogan E, Abdelraheim A et al (2012) Annual outpatient hysteroscopy and endometrial sampling (OHES) in HNPCC/Lynch syndrome (LS). Arch Gynecol Obstet 286:1555–1562PubMedCrossRefGoogle Scholar
  19. 19.
    Bouquier J, Blons H, Narjoz C, Lecuru F, Laurent-Puig P, Bats AS (2011) Microsatellite instability analysis in uterine cavity washings as a screening tool for endometrial cancer in Lynch syndrome. Fam Cancer 10:655–657PubMedCrossRefGoogle Scholar
  20. 20.
    Lindor NM, Petersen GM, Hadley DW et al (2006) Recommendations for the care of individuals with an inherited predisposition to Lynch syndrome: a systematic review. JAMA 296:1507–1517PubMedCrossRefGoogle Scholar
  21. 21.
    NCCN Guidelines Version 2.2012 Lynch Syndrome. 2012. (Accessed at www.nccn.org.)
  22. 22.
    Huang M, Sun C, Boyd-Rogers S et al (2011) Prospective study of combined colon and endometrial cancer screening in women with lynch syndrome: a patient-centered approach. J Oncol Pract Am Soc Clin Oncol 7:43–47CrossRefGoogle Scholar
  23. 23.
    Weiss NS, Sayvetz TA (1980) Incidence of endometrial cancer in relation to the use of oral contraceptives. N Engl J Med 302:551–554PubMedCrossRefGoogle Scholar
  24. 24.
    Lu K L-mC, Lynch H, Yates MS, Nogueras-Gonzalez GM, Munsell MF, Cornelison T, Boyd-Rogers S, Rubin M, Daniels MS, Conrad P, Milbourne A, Gershenson D, Loose D, Broaddus RR (In press) A prospective, multi-center randomized study of oral contraceptive vs. Depo-Provera for the prevention of endometrial cancer in women with Lynch syndrome. Cancer Prev ResGoogle Scholar
  25. 25.
    Hankinson SE, Colditz GA, Hunter DJ, Spencer TL, Rosner B, Stampfer MJ (1992) A quantitative assessment of oral contraceptive use and risk of ovarian cancer. Obstet Gynecol 80:708–714PubMedGoogle Scholar
  26. 26.
    The reduction in risk of ovarian cancer associated with oral-contraceptive use. The Cancer and Steroid Hormone Study of the Centers for Disease Control and the National Institute of Child Health and Human Development. N Engl J Med 1987;316:650–655Google Scholar
  27. 27.
    Schmeler KM, Lynch HT, Chen LM et al (2006) Prophylactic surgery to reduce the risk of gynecologic cancers in the Lynch syndrome. N Engl J Med 354:261–269PubMedCrossRefGoogle Scholar
  28. 28.
    Schmeler KM, Daniels MS, Soliman PT et al (2010) Primary peritoneal cancer after bilateral salpingo-oophorectomy in two patients with Lynch syndrome. Obstet Gynecol 115:432–434PubMedCrossRefGoogle Scholar
  29. 29.
    Ghezzi F, Uccella S, Cromi A, Bogani G, Donadello N, Riva C (2013) Primary peritoneal cancer in Lynch syndrome: a clinical-pathologic report of a case and analysis of the literature. Int J Gynecol Pathol 32(2):163–166Google Scholar
  30. 30.
    Vasen HF, Moslein G, Alonso A et al (2007) Guidelines for the clinical management of Lynch syndrome (hereditary non-polyposis cancer). J Med Genet 44:353–362PubMedCrossRefGoogle Scholar
  31. 31.
    Fast Stats: An interactive tool for access to SEER cancer statistics. Surveillance Research Program, National Cancer Institute. http://seer.cancer.gov/faststats. Accessed on 1 Aug 2010
  32. 32.
    Jarvinen HJ, Aarnio M, Mustonen H et al (2000) Controlled 15-year trial on screening for colorectal cancer in families with hereditary nonpolyposis colorectal cancer. Gastroenterology 118:829–834PubMedCrossRefGoogle Scholar
  33. 33.
    Chen LM, Yang KY, Little SE, Cheung MK, Caughey AB (2007) Gynecologic cancer prevention in Lynch syndrome/hereditary nonpolyposis colorectal cancer families. Obstet Gynecol 110:18–25PubMedCrossRefGoogle Scholar
  34. 34.
    Kwon JS, Sun CC, Peterson SK et al (2008) Cost-effectiveness analysis of prevention strategies for gynecologic cancers in Lynch syndrome. Cancer 113:326–335PubMedCrossRefGoogle Scholar
  35. 35.
    Yang KY, Caughey AB, Little SE, Cheung MK, Chen LM (2011) A cost-effectiveness analysis of prophylactic surgery versus gynecologic surveillance for women from hereditary non-polyposis colorectal cancer (HNPCC) Families. Fam Cancer 10:535–543PubMedCrossRefGoogle Scholar
  36. 36.
    Stuckless S, Green JS, Morgenstern M et al. (2012) Impact of colonoscopic screening in male and female Lynch syndrome carriers with an MSH2 mutation. Clin Genet 82(5):439–445Google Scholar

Copyright information

© Springer Science+Business Media Dordrecht 2013

Authors and Affiliations

  1. 1.H.E.B. Professor of Cancer Research, Department of Gynecologic Oncology and Reproductive MedicineUniversity of Texas MD Anderson Cancer CenterHoustonUSA
  2. 2.Department of Gynecologic Oncology and Reproductive MedicineUniversity of Texas MD Anderson Cancer CenterHoustonUSA

Personalised recommendations