Advertisement

Hereditary Endometrial and Ovarian Cancers

  • Garima Yadav
  • Anshuja Singla
Chapter

Abstract

Hereditary gynecological cancers including those of the endometrium and ovaries account for 5% and 12% of all these tumors, respectively. Hereditary cancers are suspected in women presenting with gynecological malignancies at a relatively young age or with a family history of cancer, usually of a specific cancer syndrome, in two or more relatives. The familial aggregation of cancers can be attributed to both genetic and environmental factors common within families, but genetic factors are thought to be more important. This chapter elaborates the genetic syndromes like hereditary nonpolyposis colorectal cancer (HNPCC) syndrome also known as Lynch syndrome, hereditary breast and ovarian cancer (HOBC) syndrome, Cowden syndrome, Li-Fraumeni syndrome, and Peutz-Jeghers syndrome, which are found to be responsible for majority of the hereditary gynecological malignancies. The screening guidelines along with the newer available diagnostic methods and treatment modalities based on the recent available evidence are discussed.

Keywords

Hereditary endometrial cancer Hereditary ovarian cancers HNPCC HOBC Cancer genetics Cancer screening 

References

  1. 1.
    Ferlay J, Shin HR, Bray F, Forman D, Mathers C, Parkin DM. Estimates of worldwide burden of cancer in 2008. Int J Cancer. 2010;127(12):2893–917.PubMedCrossRefGoogle Scholar
  2. 2.
    Berends MJ, Wu Y, Sijmons RH, et al. Toward new strategies to select young endometrial cancer patients for mismatch repair gene mutation analysis. J Clin Oncol. 2003;21:4364–70.PubMedCrossRefGoogle Scholar
  3. 3.
    King MC, Marks JH, Mandell JB. Breast and ovarian cancer risks due to inherited mutations in BRCA1 and BRCA2. Science. 2003;302:643–6.PubMedCrossRefGoogle Scholar
  4. 4.
    Stratton JF, Pharoah PDP, Smith SK, Easton DF, Ponder BAJ. A systematic review an metaanalysis of family history an risk of ovarian cancer. Br J Obstet Gynaecol. 1998;105:493–9.PubMedCrossRefGoogle Scholar
  5. 5.
    Gruber SB, Thompson WD. A population base study of endometrial cancer and familial risk in younger women. Cancer and Steroid Hormone Study Group. Cancer Epidemiol Biomark Prev. 1996;5(6):411–7.Google Scholar
  6. 6.
    Lucenteforte E, Talamini R, Montella M, Dal Maso L, Pelucchi C, Franceschi S, La Vecchia C, Negri E. Family history of cancer and risk of endometrial cancer. Eur J Cancer Prev. 2009;18(2):95–9.PubMedCrossRefGoogle Scholar
  7. 7.
    Parazzini F, Negri E, La Vecchia C, Restelli C, Francesci S. Family history of reproductive cancers and ovarian cancer risk: an Italian case control study. Am J Epidemiol. 1992;135(1):35–40.PubMedCrossRefGoogle Scholar
  8. 8.
    Lichtenstein P, Holm NV, Verkasalo PK, Iliadou A, Kaprio J, Koskenvuo M, Pukkala E, Skytthe A, Hemminki K. Environmental and heritable factors in the causation of cancer- analyses of cohorts of twins from Sweden, Denmark, Finland. N Engl J Med. 2000;343(2):78–85.PubMedPubMedCentralCrossRefGoogle Scholar
  9. 9.
    Baker VV. Update on the molecular carcinogenesis of cervix cancer. Clin Consult Obstet Gynecol. 1995;7:86–93.Google Scholar
  10. 10.
    Hogdall EV, Christensen L, Kjaer SK, et al. Distribution of HER-2 overexpression in ovarian carcinoma tissue and its prognostic value in patients with ovarian carcinoma: from the Danish MALOVA Ovarian Cancer Study. Cancer. 2003;98:66–73.PubMedCrossRefGoogle Scholar
  11. 11.
    Kastan MB, Onyekwere O, Sidransky D, et al. Participation of p53 protein in the cellular response to DNA damage. Cancer Res. 1991;51:6304–11.PubMedGoogle Scholar
  12. 12.
    Kuerbitz SJ, Plunkett BS, Walsh WV, et al. Wild type p53 is a cell cycle checkpoint determinant following irradiation. Proc Natl Acad Sci U S A. 1992;89:7491–5.PubMedPubMedCentralCrossRefGoogle Scholar
  13. 13.
    Bacolod MD, Schemmann GS, Giardina SF, et al. Emerging paradigms in cancer genetics: some important findings from high-density single nucleotide polymorphism array studies. Cancer Res. 2009;69:723–7.PubMedPubMedCentralCrossRefGoogle Scholar
  14. 14.
    Meyer LA, Broadus RR, Lu KH. Endometrial cancer and Lynch syndrome: clinical and pathologic considerations. Cancer Control. 2009;16(1):14–22.PubMedPubMedCentralCrossRefGoogle Scholar
  15. 15.
    Aarnio M, Sankila R, Pukkala E, Salovaara R, Aaltonen LA, de la Chapelle A, Peltomaki P, Mecklin JP, Jarvinen HJ. Cancer risk in mutation carriers of DNA-mismatch-repair genes. Int J Cancer. 1999;81(2):214–8.PubMedPubMedCentralCrossRefGoogle Scholar
  16. 16.
    Vasen HF, Watson P, Mecklin JP, Lynch HT. New clinical criteria for hereditary non polyposis colorectal cancer (HNPCC,Lynch syndrome) proposed by the international collaborative group on HNPCC. Gastroenterology. 1999;116(6):1453–6.PubMedPubMedCentralCrossRefGoogle Scholar
  17. 17.
    Watson P, Lynch HT. Cancer risk in mismatch repair genes mutation carriers. Familial Cancer. 2001;1:57–60.PubMedCrossRefGoogle Scholar
  18. 18.
    Dunlop MG, Farrington SM, Carothers AD, Wyllie AH, Sharp L, Burn J, Liu B, Kinzler KW, Vogelstein B. Cancer risk associated with germline DNA mismatch repair gene mutations. Hum Mol Genet. 1997;6(1):105–10.PubMedPubMedCentralCrossRefGoogle Scholar
  19. 19.
    Vasen HF, Wijnen JT, Menko FH, Kleibeuker JH, Taaal BG, Griffioen G, Nagengast FM, Meijers-Heijboer EH, Bertario L, Varesco L, et al. Cancer risk in families with hereditary nonpolyposis colorectal cancer diagnosed by mutation analysis. Gastroenterology. 1996;110(4):1020–7.PubMedCrossRefGoogle Scholar
  20. 20.
    Hendriks YM, Wagner A, Morreau H, Menko F, Stormorken A, Quehenberger F, Sandkuijl L, Moller P, Genuardi M, van Houwelingen H, et al. Cancer risk in hereditary nonpolyposis colorectal cancer ue to MSH6 mutations: impact on counseling and surveillance. Gastroenterology. 2004;127(1):17–25.PubMedCrossRefGoogle Scholar
  21. 21.
    Hampel H, Stephens JA, Pukkala E, Sankila R, Aoltonen LA, Mecklin JP, de la Chapelle A. Cancer risk in hereditary nonpolyposis colorectal cancer syndrome: later age of onset. Gastroenterology. 2005;129(20):415–21.PubMedPubMedCentralCrossRefGoogle Scholar
  22. 22.
    Baglietto L, Lindor NM, Dowty JG, White DM, Wagner A, Gomez Garcia EB, Vriends AH, Dutch Lynch Syndrome Study Group, Cartwright NR, Barnetson RA. Risk of LYNCH syndrome cancers in MSH6 mutation carriers. J Natl Cancer Inst. 2010;102(3):193–201.PubMedPubMedCentralCrossRefGoogle Scholar
  23. 23.
    Watson P, Vasen HF, Mecklin JP, Bernstein I, Aarnio M, Jarvinen HJ, Myrhoj T, Sunde L, Wijnen JT, Lynch HT. The risk of extra-colonic, extra-endometrial cancer in the Lynch syndrome. Int J Cancer. 2008;123(2):444–9.PubMedPubMedCentralCrossRefGoogle Scholar
  24. 24.
    Vasen HF, Stormorken A, Menko FH, Nageggast FM, Kleibeuker JH, Griffioen G, Taal BG, Moller P, Wijnen JT. MSH2 mutation carriers are at higher risk of cancer than MLH1 mutation carriers: a study of hereditary non polyposis colorectal cancer families. J Clin Oncol. 2001;19:4074–80.PubMedCrossRefGoogle Scholar
  25. 25.
    Malander S, Rambech E, Kristoffersson U, Halvarsson B, Ridderheim M, Borg A, Nilbert M. The contribution of the hereditary non polyposis colorectal cancer syndrome to the development of ovarian cancer. Gynecol Oncol. 2006;101:238–43.PubMedCrossRefGoogle Scholar
  26. 26.
    Rubin SC, Blackwood MA, Bandera C, Behbakht K, Benjamin I, Rebbeck TR, Boyd J. BRCA1, BRCA 2, and hereditary nonpolyposis colorectal cancer gene mutations in an unselected ovarian cancer population: relationship to family history and implications for genetic testing. Am J Obstet Gynecol. 1998;178:670–7.PubMedPubMedCentralCrossRefGoogle Scholar
  27. 27.
    Lu KH, Schorge JO, Roabaugh KJ, Daniels MS, Sun CC, Soliman PT, White KG, Luthra R, Gershenson DM, Broaddus RR. Prospective determination of prevalence of Lynch syndrome in young women with endometrial cancer. J Clin Oncol. 2007;25:5158–64.PubMedCrossRefGoogle Scholar
  28. 28.
    Berends MJ, Wu Y, Sijmons RH, van der Sluis T, Ek WB, Ligtenberg MJ, Arts NJ, ten Hoor KA, Kleibeuker JH, de Vries EG, et al. Toward new strategies to select endometrial cancer patients for mis-match repair gene mutation analysis. J Clin Oncol. 2003;21:4364–70.PubMedCrossRefGoogle Scholar
  29. 29.
    Ollikainen M, Abdel-Rehman WM, M oisio AL, Lindroos A, Kariola R, Jarvela I, Poyhonen M, Butzow R, Peltomaki P. Molecular analysis of familial endometrial carcinoma: a manifestation of hereditary nonpolyposis colorectal cancer or a separate syndrome? J Clin Oncol. 2005;23:4609–16.PubMedCrossRefGoogle Scholar
  30. 30.
    Vasen HF, Blanco I, Aktan-Collan K, Gopie JP, Alonso A, Aretz S, et al. Revised guidelines for the clinical management of Lynch syndrome (HNPCC): recommendations by a group of European experts. Gut. 2013;62:812–23.PubMedPubMedCentralCrossRefGoogle Scholar
  31. 31.
    Schmeler KM, Lynch HT, Chen LM, Munsell MF, Soliman PT, Clark MB, et al. Prophylactic surgery to reduce the risk of gynecologic cancers in the Lynch syndrome. N Engl J Med. 2006;354:261–9.PubMedPubMedCentralCrossRefGoogle Scholar
  32. 32.
    Eng C. Will the real cowden syndrome please stand up: revised diagnostic criteria. J Med Genet. 2000;37:828–30.PubMedPubMedCentralCrossRefGoogle Scholar
  33. 33.
    Gayther SA, Russell P, Harrington P, Antoniou A, Easton DF, Ponder BAJ. The contribution of germline BRCA1 and BRCA2 mutations to familial ovarian cancer: no evience for other ovarian cancer susceptibility genes. Am J Hum Genet. 1999;65:1021–9.PubMedPubMedCentralCrossRefGoogle Scholar
  34. 34.
    Ramus SJ, Harrington PA, Pye C, Dicioccio RA, Cox MJ, Garlinghouse-Jones K, Oakley-Girvan I, Jacobs IJ, Hardy RM, Whittemore AS, et al. Contribution of BRCA1 and BRCA2 mutations to inherited ovarian cancer. Hum Mutat. 2007;28(12):1207–15.PubMedCrossRefGoogle Scholar
  35. 35.
    Antoniou AC, Sinilnikova OM, Simard J, Leone M, Dumont M, Neuhausen SL, Struewing JP, Stoppa-Lyonnet DD, Barjhoux L, Hughes DJ, et al. RAD51 135G>C modifies breast cancer risk among BRCA2 mutation carriers: results from a combined analysis of 19 studies. Am J Hum Genet. 2007;81(6):1186–200.PubMedPubMedCentralCrossRefGoogle Scholar
  36. 36.
    Antoniou AC, Spurdle AB, Sinilnikova OM, Healey S, Pooley KA, Schmutzler RK, Versmold B, Engel C, Meindl A, Arnold N, et al. Common breast cancer predisposition alleles are associated with breast cancer risk in BRCA1 and BRCA2 mutation carriers. Am J Hum Genet. 2008;82(4):937–48.PubMedPubMedCentralCrossRefGoogle Scholar
  37. 37.
    Kurman RJ. Origin and molecular pathogenesis of ovarian high grade serous carcinoma. Ann Oncol. 2013;10:1016–21.Google Scholar
  38. 38.
    Kurman RJ, Shih IM. Pathogenesis of ovarian cancer: lessons from morphology and molecular biology and their clinical implications. Int J Gynecol Pathol. 2008;27(2):151–60.PubMedPubMedCentralGoogle Scholar
  39. 39.
    Sama AR, Schilder RJ. Refractory fallopian tube carcinoma—current perspectives in pathogenesis and management. Int J Women’s Health. 2013;6(1):149–57.Google Scholar
  40. 40.
    Walsh T, Casadie S, Lee MK, Penil CC, Nord AS, Thornton AM, et al. Mutations in 12 genes for inherited ovarian, fallopian tube, and peritoneal carcinoma identified by massive parallel sequencing. Proc Natl Acad Sci U S A. 2011;108(44):18032.PubMedPubMedCentralCrossRefGoogle Scholar
  41. 41.
    Trainer AH, Meiser B, Watts K, Mitchell G, Tucker K, Friedlander M. Moving toward personalized medicine: treatment-focused genetic testing of women newly diagnosed with ovarian cancer. Int J Gynecol Cancer. 2010;20:704–16.PubMedCrossRefGoogle Scholar
  42. 42.
    Castéra L, Krieger S, Rousselin A, Legros A, Baumann JJ, Bruet O, et al. Next-generation sequencing for the diagnosis of hereditary breast and ovarian cancer using genomic capture targeting multiple candidate genes. Eur J Hum Genet. 2014;22(11):1305–13.PubMedPubMedCentralCrossRefGoogle Scholar
  43. 43.
    Tung N, Battelli C, Allen B, Kaldate R, Bhatnagar S, Bowles K, et al. Frequency of mutations in individuals with breast cancer referred for BRCA1 and BRCA2 testing using next-generation sequencing with a 25-gene panel. Cancer. 2015;121(1):25–33.PubMedCrossRefGoogle Scholar
  44. 44.
    Ruiz A, Llort G, Yagüe C, Baena N, Viñas M, Torra M, et al. Genetic testing in hereditary breast and ovarian Cancer using massive parallel sequencing. Biomed Res Int. 2014;2014:542541, 8 pPubMedPubMedCentralGoogle Scholar
  45. 45.
    Manchanda R, Abdelraheim A, Johnson M, Rosenthal AN, Benjamin E, Brunell C, et al. Outcome of risk-reducing salpingo-oophorectomy in BRCA carriers and women of unknown mutation status. BJOG. 2011;118:814–24.PubMedCrossRefGoogle Scholar
  46. 46.
    Kauff ND, Satagopan JM, Robson ME, Scheuer L, Hensley M, Hudis CA, et al. Risk- reducing salpingo- oophorectomy in women with a BRCA1 or BRCA2 mutation. N Engl J Med. 2002;346:1609–15.PubMedCrossRefGoogle Scholar
  47. 47.
    Rebbeck TR, Lynch HT, Neuhausen SL, Narod SA, van’t Veer L, Garber JE, et al. Prophylactic oophorectomy in carriers of BRCA1 or BRCA2 mutations. N Engl J Med. 2002;346:1616–22.PubMedCrossRefGoogle Scholar
  48. 48.
    Kauff ND, Domchek SM, Friebel TM, Robson ME, Lee J, Garber JE, et al. Risk-reducing salpingo-oophorectomy for the prevention of BRCA1- and BRCA2-associated breast and gynecologic cancer: a multicenter, prospective study. J Clin Oncol. 2008;26:1331–7.PubMedPubMedCentralCrossRefGoogle Scholar
  49. 49.
    Finch A, Beiner M, Lubinski J, Lynch HT, Moller P, Rosen B, et al. Salpingo-oophorectomy and the risk of ovarian, fallopian tube, and peritoneal cancers in women with a BRCA1 or BRCA2 mutation. JAMA. 2006;296:185.PubMedPubMedCentralCrossRefGoogle Scholar
  50. 50.
    Ford D, Easton DF, Stratton M, Narod S, Goldgar D, Devilee P, et al. Genetic heterogeneity and penetrance analysis of the BRCA1 and BRCA2 genes in breast cancer families. Am J Hum Genet. 1998;62:676–89.PubMedPubMedCentralCrossRefGoogle Scholar
  51. 51.
    Rosenthal AN, Fraser L, Manchanda R, Badman P, Philpott S, Mozersky J, Hadwin R, Cafferty FH, Benjamin E, Singh N, Evans DG, Eccles DM, Skates SJ, Mackay J, Menon U, Jacobs IJ. Results of annual screening in phase I of the United Kingdom familial ovarian cancer screening study highlight the need for strict adherence to screening schedule. J Clin Oncol. 2013;31(1):49–57.PubMedCrossRefGoogle Scholar
  52. 52.
    Dziadkowiec KN, Gąsiorowska E, Markwitz EN, Jankowska A. PARP inhibitors: review of mechanisms of action and BRCA1/2 mutation targeting. Prz Menopauzalny. 2016;15(4):215–9.PubMedGoogle Scholar
  53. 53.
    Sorrell AD, Espenschied CR, Culver JO, Weitzel JN. Tumor protein p53 (TP 53) testing and li-fraumeni syndrome: current status of clinical applications and future directions. Mol Diagn Ther. 2013;17(1):31–47.PubMedPubMedCentralCrossRefGoogle Scholar
  54. 54.
    Olivier M, Goldgar DE, Sodha N, et al. Li-Fraumeni and related syndromes: correlation between tumor type, family structure, and TP53 genotype. Cancer Res. 2003;63(20):6643–50.PubMedGoogle Scholar
  55. 55.
    Giardiello FM, Trimbath JD. Peutz-Jeghers syndrome and management recommendations. Clin Gastroenterol Hepatol. 2006;4:408–15.PubMedCrossRefGoogle Scholar
  56. 56.
    Hall MJ, Innocent J, Rybak C, Veloski C, Scott WJ, Wu H, et al. Bilateral granulosa cell tumors: a novel malignant manifestation of multiple endocrine neoplasia 1 syndrome found in a patient with a rare menin in-frame deletion. Appl Clin Genet. 2015;8:69–73.PubMedPubMedCentralGoogle Scholar
  57. 57.
    Stratakis CA. Clinical genetics of multiple endocrine neoplasias, carney complex and related syndromes. J Endocrinol Investig. 2001;24:370–83.CrossRefGoogle Scholar
  58. 58.
    Jones B, Oh C, Mangold E, Egan CA. Muir–Torre syndrome: diagnostic and screening guidelines. Aust J Dermatol. 2006;47:266–9.CrossRefGoogle Scholar
  59. 59.
    Pancholi A, Collins D, Lindley R, Gandhi P. Muir–Torre syndrome: a case report and screening recommendations. Ann R Coll Surg Engl. 2008;90(8):W9–1.PubMedPubMedCentralCrossRefGoogle Scholar
  60. 60.
    Karanian-Philippe M, Velasco V, Longy M, Floquet A, Arnould L, Coindre JM, et al. SMARCA4 (BRG1) loss of expression is a useful marker for the diagnosis of ovarian small cell carcinoma of the hypercalcemic type (ovarian rhabdoid tumor): a comprehensive analysis of 116 rare gynecologic tumors, 9 soft tissue tumors, and 9 melanomas. Am J Surg Pathol. 2015;39:1197–205.PubMedCrossRefGoogle Scholar
  61. 61.
    Harrison ML, Hoskins P, du Bois A, Quinn M, Rustin GJ, Ledermann JA, Baron-Hay S, Friedlander ML. Small cell of the ovary, hypercalcemic type—analysis of combined experience and recommendation for management. A GCIG study. Gynecol Oncol. 2006;100:233–8.PubMedCrossRefGoogle Scholar

Copyright information

© Springer Nature Singapore Pte Ltd. 2019

Authors and Affiliations

  • Garima Yadav
    • 1
  • Anshuja Singla
    • 2
  1. 1.Department of Obstetrics and GynaecologyAll India Institute of Medical SciencesJodhpurIndia
  2. 2.Department of Obstetrics and GynaecologyUniversity College of Medical Sciences and Guru Teg Bahadur HospitalNew DelhiIndia

Personalised recommendations