Hereditary Risk for Cancer

  • Kate Shane-Carson
  • Joanne M. JeterEmail author


Cancer prevention consists of understanding cancer incidence in populations, identifying appropriate risk factors for specific cancers, stratifying individuals according to these risk factors, and applying effective interventions to individuals (and sometimes populations) according to their risk status. Evaluation of hereditary risk of cancer is a vital component of risk stratification. Appropriate assessment of hereditary genetic risk can lead to significant changes in the clinical management of individuals who are found to have a hereditary cancer syndrome; conversely, it can identify individuals who are not at elevated risk despite having a strong familial history of cancer. Through cancer risk evaluation, with or without genetic testing for hereditary cancer syndromes, individuals with inherited genetic changes associated with increased predisposition of cancer can be identified prior to the development or diagnosis of cancer. Determining that an individual has a strong inherited predisposition to cancer provides an opportunity to intervene with prevention and screening strategies documented to reduce cancer incidence, morbidity, or mortality.


Genetic counseling Hereditary cancers Cancer risk assessment BRCA Hereditary breast and ovarian cancer Lynch syndrome Hereditary nonpolyposis colorectal cancer 



The authors are indebted to Katherine S. Hunt, CGC, and Jessica Ray, CGC, for their work on previous versions of this chapter.


  1. Aarnio M, Sankila R et al (1999) Cancer risk in mutation carriers of DNA-mismatch-repair genes. Int J Cancer 81(2):214–218PubMedCrossRefPubMedCentralGoogle Scholar
  2. ACOG (1997) ACOG committee opinion. Breast—ovarian cancer screening. Number 176, October 1996. Committee on Genetics. The American College of Obstetricians and Gynecologists. Int J Gynaecol Obstet 56(1):82–83CrossRefGoogle Scholar
  3. Ad Hoc Committee on Genetic Counseling (1975) Genetic counseling. Am J Hum Genet 27(2):240–242Google Scholar
  4. Ajani JA et al (2017) Referenced with permission from the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) for Gastric Cancer V.5.2017. © National Comprehensive Cancer Network, Inc. 2017. All rights reserved. Accessed 4 Mar 2018. To view the most recent and complete version of the guideline, go online to
  5. Amos C, Frazier M, McGarrity T (2007) Peutz-Jeghers syndrome. In: GeneReviews., University of Washington. Accessed 27 Mar 2008
  6. Antoniou AC, Casadei S et al (2014) Breast-cancer risk in families with mutations in PALB2. N Engl J Med 371(6):497–506PubMedPubMedCentralCrossRefGoogle Scholar
  7. ASCO (2003) American Society of Clinical Oncology policy statement update: genetic testing for cancer susceptibility. J Clin Oncol 21(12):2397–2406CrossRefGoogle Scholar
  8. ASHG (1994) Statement of the American Society of Human Genetics on genetic testing for breast and ovarian cancer predisposition. Am J Hum Genet 55(5):i–ivGoogle Scholar
  9. Baker LH (1982) Breast Cancer Detection Demonstration Project: five-year summary report. CA Cancer J Clin 32(4):194–225PubMedCrossRefPubMedCentralGoogle Scholar
  10. Bane AL, Beck JC, Bleiweiss I et al (2007) BRCA2 mutation-associated breast cancers exhibit a distinguishing phenotype based on morphology and molecular profiles from tissue microarrays. Am J Surg Pathol 31:121–128PubMedCrossRefPubMedCentralGoogle Scholar
  11. Barnes-Kedar IM, Plon SE (2002) Counseling the at risk patient in the BRCA1 and BRCA2 era. Obstet Gynecol Clin N Am 29(2):341–366. viiCrossRefGoogle Scholar
  12. Berg WA, Bandos AI et al (2015) Ultrasound as the primary screening test for breast cancer: analysis from ACRIN 6666. J Natl Cancer Inst 108(4):djv367PubMedPubMedCentralCrossRefGoogle Scholar
  13. Blanco A, de la Hoya M et al (2013) Analysis of PALB2 in BRCA1/BRCA2 negative Spanish hereditary breast/ovarian cancer families with pancreatic cancer cases. PLoS One 8(7):e67538PubMedPubMedCentralCrossRefGoogle Scholar
  14. Boardman LA, Thibodeau SN et al (1998) Increased risk for cancer in patients with the Peutz-Jeghers syndrome. Ann Intern Med 128(11):896–899PubMedCrossRefPubMedCentralGoogle Scholar
  15. Bonadona V et al (2011) Cancer risks associated with germline mutations in MLH1, MSh2, and MSH6 genes in Lynch syndrome. J Am Med Assoc 305(22):2304–2310CrossRefGoogle Scholar
  16. Brooks-Wilson AR et al (2004) Germline E-cadherin mutations in hereditary diffuse gastric cancer: assessment of 42 new families and review of genetic screening criteria. J Med Genet 41:508–517PubMedPubMedCentralCrossRefGoogle Scholar
  17. Burke W, Daly M et al (1997) Recommendations for follow-up care of individuals with an inherited predisposition to cancer. II. BRCA1 and BRCA2. Cancer Genetics Studies Consortium. JAMA 277(12):997–1003PubMedCrossRefPubMedCentralGoogle Scholar
  18. Burn J, Gerdes AM et al (2011) Long-term effect of aspirin on cancer risk in carriers of hereditary colorectal cancer: an analysis from the CAPP2 randomized clinical trial. Lancet 378:2081–2208PubMedPubMedCentralCrossRefGoogle Scholar
  19. Buys SS, Sandbach JF et al (2017) A study of over 35,000 women with breast cancer tested with a 25-gene panel of hereditary cancer genes. Cancer 123(10):1721–1730PubMedCrossRefPubMedCentralGoogle Scholar
  20. Canto MI, Harinck F et al (2013) International Cancer of the Pancreas Screening (CAPS) Consortium summit on the management of patients with increased risk for familial pancreatic cancer. Gut 62(3):339–347PubMedCrossRefPubMedCentralGoogle Scholar
  21. Casadei S, Norquist BM et al (2011) Contribution of inherited mutations in the BRCA2-interacting protein PALB2 to familial breast cancer. Cancer Res 71(6):2222–2229PubMedPubMedCentralCrossRefGoogle Scholar
  22. Chompret A, Abel A et al (2001) Sensitivity and predictive value of criteria for p53 germline mutation screening. J Med Genet 38:43–47PubMedPubMedCentralCrossRefGoogle Scholar
  23. Claus EB, Risch N et al (1994) Autosomal dominant inheritance of early-onset breast cancer. Implications for risk prediction. Cancer 73(3):643–651PubMedCrossRefPubMedCentralGoogle Scholar
  24. Couch FJ, Weber BL et al (1996) Mutations and polymorphisms in the familial early-onset breast cancer (BRCA1) gene. Hum Mutat 8(1):8–18PubMedCrossRefPubMedCentralGoogle Scholar
  25. Cybulski C, Wokolorczyk D et al (2011) Risk of breast cancer in women with a CHEK2 mutation with and without a family history of breast cancer. J Clin Oncol 29(28):3747–3752PubMedCrossRefPubMedCentralGoogle Scholar
  26. Daly MB et al (2018) Referenced with permission from the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) for Genetic/Familial High Risk Assessment: Breast and Ovarian V.1.2018. © National Comprehensive Cancer Network, Inc. 2018. All rights reserved. Accessed 4 Mar 2018. To view the most recent and complete version of the guideline, go online to
  27. Desmond A, Kurian AW et al (2015) Clinical actionability of multigene panel testing for hereditary breast and ovarian cancer risk assessment. JAMA Oncol 1(7):943–951PubMedPubMedCentralCrossRefGoogle Scholar
  28. Domchek SM, Eisen A et al (2003) Application of breast cancer risk prediction models in clinical practice. J Clin Oncol 21(4):593–601PubMedCrossRefPubMedCentralGoogle Scholar
  29. Dunlop MG, Farrington SM et al (1997) Cancer risk associated with germline DNA mismatch repair gene mutations. Hum Mol Genet 6(1):105–110PubMedCrossRefPubMedCentralGoogle Scholar
  30. EGAPP Working Group (2009) Recommendations from the EGAPP Working Group: genetic testing strategies in newly diagnosed individuals with colorectal cancer aimed at reducing morbidity and mortality from Lynch syndrome in relatives. Genet Med 11:35–41CrossRefGoogle Scholar
  31. Eggington JM, Bowles KR et al (2014) A comprehensive laboratory-based program for classification of variants of uncertain significance in hereditary cancer genes. Clin Genet 86(3):229–237PubMedCrossRefGoogle Scholar
  32. Eisen A, Lubinski J et al (2008) Hormone therapy and the risk of breast cancer in BRCA1 mutation carriers. J Natl Cancer Inst 100:1361–1367PubMedPubMedCentralCrossRefGoogle Scholar
  33. Eng C (2000) Will the real Cowden syndrome please stand up: revised diagnostic criteria. J Med Genet 37(11):828–830PubMedPubMedCentralCrossRefGoogle Scholar
  34. Evans DG, Susnerwala I et al (2010) Risk of breast cancer in male BRCA2 carriers. J Med Genet 47(10):710–711PubMedCrossRefGoogle Scholar
  35. Fackenthal JD, Marsh DJ et al (2001) Male breast cancer in Cowden syndrome patients with germline PTEN mutations. J Med Genet 38(3):159–164PubMedPubMedCentralCrossRefGoogle Scholar
  36. Fearon ER, Vogelstein B (1990) A genetic model for colorectal tumorigenesis. Cell 61(5):759–767PubMedCrossRefGoogle Scholar
  37. Fisher B et al (2005) Tamoxifen for the prevention of breast cancer: current status of the National Surgical Adjuvant Breast and Bowel Project P-1 study. J Natl Cancer Inst 97:1652–1662PubMedCrossRefGoogle Scholar
  38. Ford D, Easton DF et al (1994) Risks of cancer in BRCA1-mutation carriers. Lancet 343(8899):692–695PubMedCrossRefPubMedCentralGoogle Scholar
  39. Frank TS, Manley SA et al (1998) Sequence analysis of BRCA1 and BRCA2: correlation of mutations with family history and ovarian cancer risk. J Clin Oncol 16(7):2417–2425PubMedCrossRefPubMedCentralGoogle Scholar
  40. Franks LM, Teich NM (1997) Introduction to the cellular and molecular biology of cancer. Oxford University Press, LondonGoogle Scholar
  41. Geller G, Botkin JR et al (1997) Genetic testing for susceptibility to adult-onset cancer. The process and content of informed consent. JAMA 277(18):1467–1474PubMedCrossRefPubMedCentralGoogle Scholar
  42. Giardiello FM, Brensinger JD et al (1997) The use and interpretation of commercial APC gene testing for familial adenomatous polyposis. N Engl J Med 336(12):823–827PubMedCrossRefPubMedCentralGoogle Scholar
  43. Gonzalez-Angulo AM, Timms KM et al (2011) Incidence and outcome of BRCA mutations in unselected patients with triple receptor-negative breast cancer. Clin Cancer Res 17(5):1082–1089PubMedPubMedCentralCrossRefGoogle Scholar
  44. Goss PE, Ingle JN et al (2011) Exemestane for breast cancer prevention in postmenopausal women. N Engl J Med 364(25):2381–2391PubMedCrossRefPubMedCentralGoogle Scholar
  45. Hall JM, Lee MK et al (1990) Linkage of early-onset familial breast cancer to chromosome-17q21. Science 250(4988):1684–1689PubMedCrossRefPubMedCentralGoogle Scholar
  46. Hall MJ, Forman AD et al (2014) Gene panel testing for inherited cancer risk. J Natl Compr Cancer Netw 12(9):1339–1346CrossRefGoogle Scholar
  47. Hampel H, Peltomaki P (2000) Hereditary colorectal cancer: risk assessment and management. Clin Genet 58(2):89–97PubMedCrossRefGoogle Scholar
  48. Hampel H, Bennett RL et al (2015) A practice guideline from the American College of Medical Genetics and Genomics and the National Society of Genetic Counselors: referral indications for cancer predisposition assessment. Genet Med 17(1):70–87PubMedCrossRefGoogle Scholar
  49. Hartmann LC, Sellers TA et al (1999) Clinical options for women at high risk for breast cancer. Surg Clin North Am 79(5):1189–1206PubMedCrossRefGoogle Scholar
  50. Heemskerk-Gerritsen BA et al (2015) Breast cancer risk after salpingo-oophorectomy in healthy BRCA1/2 mutation carriers: revisiting the evidence for risk reduction. J Natl Cancer Inst 107(5):djv033PubMedCrossRefPubMedCentralGoogle Scholar
  51. Heijnsdijk EA, Warner E et al (2012) Differences in natural history between breast cancers in BRCA1 and BRCA2 mutation carriers and effects of MRI screening—MRISC, MARIBS, and Canadian studies combined. Cancer Epidemiol Biomark Prev 21(9):1458–1468CrossRefGoogle Scholar
  52. Hemminki A (1999) The molecular basis and clinical aspects of Peutz-Jeghers syndrome. Cell Mol Life Sci 55(5):735–750PubMedCrossRefPubMedCentralGoogle Scholar
  53. Hemminki A, Markie D et al (1998) A serine/threonine kinase gene defective in Peutz-Jeghers syndrome. Nature 391(6663):184–187PubMedCrossRefPubMedCentralGoogle Scholar
  54. Herrmann LJ, Heinze B et al (2012) TP53 germline mutations in adult patients with adrenocortical carcinoma. J Clin Endocrinol Metab 97(3):E476–E485PubMedCrossRefPubMedCentralGoogle Scholar
  55. Howlett NG, Taniguchi T et al (2002) Biallelic inactivation of BRCA2 in Fanconi anemia. Science 297(5581):606–609PubMedCrossRefPubMedCentralGoogle Scholar
  56. Izatt L, Greenman J et al (1999) Identification of germline missense mutations and rare allelic variants in the ATM gene in early-onset breast cancer. Genes Chromosomes Cancer 26(4):286–294PubMedCrossRefPubMedCentralGoogle Scholar
  57. Jenkins MA et al (2006) Risk of colorectal cancer in monoallelic and biallelic carriers of MYH mutations: a population based case–family study. Cancer Epidemiol Biomark Prev 15(2):312–314CrossRefGoogle Scholar
  58. Kapoor NS, Curcio LD et al (2015) Multigene panel testing detects equal rates of pathogenic BRCA 1/2 mutations and has a higher diagnostic yield compared to limited BRCA 1/2 analysis alone in patients at risk for hereditary breast cancer. Ann Surg Oncol 22(10):3282–3288PubMedCrossRefPubMedCentralGoogle Scholar
  59. Kaufman B et al (2014) Olaparib monotherapy in patients with advanced cancer and a germline BRCA1/2 mutation. J Clin Oncol 33:244–250PubMedPubMedCentralCrossRefGoogle Scholar
  60. Kempers MJ, Kuiper RP et al (2011) Risk of colorectal and endometrial cancers in EPCAM deletion-positive Lynch syndrome: a cohort study. Lancet Oncol 12:49–55PubMedCrossRefPubMedCentralGoogle Scholar
  61. King JE, Dozois RR et al (2000) Care of patients and their families with familial adenomatous polyposis. Mayo Clin Proc 75(1):57–67PubMedCrossRefPubMedCentralGoogle Scholar
  62. King MC et al (2001) Tamoxifen and breast cancer incidence among women with inherited mutations in BRCA1 and BRCA2: National Surgical Adjuvant Breast and Bowel Project (NSABP–P1) Breast Cancer Prevention Trial. JAMA 286:2251–2256PubMedCrossRefPubMedCentralGoogle Scholar
  63. King MC, Marks JH et al (2003) Breast and ovarian cancer risks due to inherited mutations in BRCA1 and BRCA2. Science 302(5645):643–646PubMedPubMedCentralCrossRefGoogle Scholar
  64. Klitzman R, Chung W et al (2013) Attitudes and practices among internists concerning genetic testing. J Genet Couns 22(1):90–100PubMedCrossRefPubMedCentralGoogle Scholar
  65. Knudson AG (1971) Mutation and cancer—statistical study of retinoblastoma. Proc Natl Acad Sci U S A 68(4):820–823PubMedPubMedCentralCrossRefGoogle Scholar
  66. Kriege M, Brekelmans CT et al (2004) Efficacy of MRI and mammography for breast-cancer screening in women with a familial or genetic predisposition. N Engl J Med 351(5):427–437PubMedCrossRefPubMedCentralGoogle Scholar
  67. LaDuca H, Stuenkel AJ et al (2014) Utilization of multigene panels in hereditary cancer predisposition testing: analysis of more than 2,000 patients. Genet Med 16(11):830–837PubMedPubMedCentralCrossRefGoogle Scholar
  68. Le DT et al (2015) PD-1 blockade I tumors with mismatch repair deficiency. N Engl J Med 372:2509–2520PubMedPubMedCentralCrossRefGoogle Scholar
  69. Li FP, Fraumeni JF Jr et al (1988) A cancer family syndrome in twenty-four kindreds. Cancer Res 48:5358–5362PubMedPubMedCentralGoogle Scholar
  70. Libe R, Bertherat J (2005) Molecular genetics of adrenocortical tumours, from familial to sporadic diseases. Eur J Endocrinol 153(4):477–487PubMedCrossRefPubMedCentralGoogle Scholar
  71. Loveday CM et al (2011) Germline mutations in RAD51D confer susceptibility to ovarian cancer. Nat Genet 43(9):879–882PubMedPubMedCentralCrossRefGoogle Scholar
  72. Loveday C et al (2012) Germline RAD51C mutations confer susceptibility to ovarian cancer. Nat Genet 44(5):475–476PubMedCrossRefPubMedCentralGoogle Scholar
  73. Lynch HT, Lynch JF (1998) Genetics of colonic cancer. Digestion 59(5):481–492PubMedCrossRefPubMedCentralGoogle Scholar
  74. Lynch HT, Lynch JF (2000) Hereditary nonpolyposis colorectal cancer. Semin Surg Oncol 18(4):305–313PubMedCrossRefPubMedCentralGoogle Scholar
  75. Madalinska JBM et al (2007) Predictors of prophylactic bilateral salpingo-oophorectomy compared with gynecologic screening use in BRCA1/2 mutation carriers. J Clin Oncol 25:301–307PubMedCrossRefPubMedCentralGoogle Scholar
  76. Malander S, Ridderheim M et al (2004) One in 10 ovarian cancer patients carry germ line BRCA1 or BRCA2 mutations: results of a prospective study in Southern Sweden. Eur J Cancer 40(3):422–428PubMedCrossRefPubMedCentralGoogle Scholar
  77. Marabelli M et al (2016) Penetrance of ATM gene mutations in breast cancer: A meta-analysis of different measures of risk. Genet Epidemiol 40(5):425–431PubMedCrossRefPubMedCentralGoogle Scholar
  78. McCuaig JM et al (2012) Routine TP53 testing for breast cancer under age 30: Ready for prime time? Familial Cancer 11(4):607–613PubMedCrossRefPubMedCentralGoogle Scholar
  79. Meijers-Heijboer H et al (2002) Low-penetrance susceptibility to breast cancer due to CHEK2 1100delC in noncarriers of BRCA1 or BRCA2 mutations. Nat Genet 31:55–59PubMedCrossRefPubMedCentralGoogle Scholar
  80. Miki Y, Swensen J et al (1994) Isolation of BRCA1, the 17q-linked breast and ovarian cancer susceptibility gene. Science 266:61–71CrossRefGoogle Scholar
  81. Moller P et al (2017) Cancer risk and survival in path MMR carriers by gene and gender up to 75 years of age: a report from the Prospective Lynch Syndrome Database. Gut 66(9):1657–1664PubMedCrossRefPubMedCentralGoogle Scholar
  82. Narod SA, Risch H et al (1998) Oral contraceptives and the risk of hereditary ovarian cancer. Hereditary Ovarian Cancer Clinical Study Group. N Engl J Med 339(7):424–428PubMedCrossRefPubMedCentralGoogle Scholar
  83. NCI (1998) Breast cancer risk assessment tool for health care providers. N. C. I. Office of Cancer Communication, BethesdaGoogle Scholar
  84. NCI (2007) Breast cancer risk assessment tool. Accessed 21 Feb 2018
  85. Nelen MR, Padberg GW et al (1996) Localization of the gene for Cowden disease to chromosome 10q22-23. Nat Genet 13(1):114–116PubMedCrossRefPubMedCentralGoogle Scholar
  86. Nelson HD, Huffman LH, Fu R, Harris EL, U.S. Preventive Services Task Force (2005) Genetic risk assessment and BRCA mutation testing for breast and ovarian cancer susceptibility: systematic evidence for review for the US Preventive Services Task Force. Ann Intern Med 143:362–379PubMedCrossRefPubMedCentralGoogle Scholar
  87. Nussbaum RL, McInnes RR, Willard HF (2001) Thompson and Thompson genetics in medicine. W.B. Saunders Company, PhiladelphiaGoogle Scholar
  88. Offit K (1997) Clinical cancer genetics: risk counseling and management. Wiley-Liss, New YorkGoogle Scholar
  89. Parmigiani G, Wang W (2004) BRCAPRO. B. Lab, Accessed 10 Nov 2004
  90. Parmigiani G, Berry D et al (1998) Determining carrier probabilities for breast cancer-susceptibility genes BRCA1 and BRCA2. Am J Hum Genet 62(1):145–158PubMedPubMedCentralCrossRefGoogle Scholar
  91. Peelen T, vanVliet M et al (1997) A high proportion of novel mutations in BRCA1 with strong founder effects among Dutch and Belgian hereditary breast and ovarian cancer families. Am J Hum Genet 60(5):1041–1049PubMedPubMedCentralGoogle Scholar
  92. Peelen T, de Leeuw W et al (2000) Genetic analysis of a breast-ovarian cancer family, with 7 cases of colorectal cancer linked to BRCA1, fails to support a role for BRCA1 in colorectal tumorigenesis. Int J Cancer 88(5):778–782PubMedCrossRefPubMedCentralGoogle Scholar
  93. Peltomaki P, Vasen HF (1997) Mutations predisposing to hereditary nonpolyposis colorectal cancer: database and results of a collaborative study. The International Collaborative Group on Hereditary Nonpolyposis Colorectal Cancer. Gastroenterology 113(4):1146–1158PubMedCrossRefPubMedCentralGoogle Scholar
  94. Peters JA, Stopfer JE (1996) Role of the genetic counselor in familial cancer. Oncology (Williston Park) 10(2):159–166Google Scholar
  95. Pilarski R et al (2013) Cowden syndrome and the PTEN hamartoma tumor syndrome: Systematic review and revised diagnostic criteria. J Natl Cancer Inst 105(21):1607–1616PubMedCrossRefPubMedCentralGoogle Scholar
  96. Provenzale D, et al (2017) Referenced with permission from the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) for Genetic/Familial High Risk Assessment: Colorectal V.1.2018. © National Comprehensive Cancer Network, Inc. 2018. All rights reserved. Accessed 4 Mar 2018. To view the most recent and complete version of the guideline, go online to
  97. Rafnar T et al (2011) Mutations in BRIP1 confer high risk of ovarian cancer. Nat Genet 43(11):1104–1107PubMedCrossRefPubMedCentralGoogle Scholar
  98. Raymond VM et al (2012) Prevalence of germline TP53 mutations in a prospective series of unselected patients with adrenocortical carcinoma. J Clin Endocrinol Metab 98(1):E119–E125PubMedPubMedCentralCrossRefGoogle Scholar
  99. Rebbeck TR, Friebel T et al (2004) Bilateral prophylactic mastectomy reduces breast cancer risk in BRCA1 and BRCA2 mutation carriers: the PROSE Study Group. J Clin Oncol 22(6):1055–1062PubMedCrossRefPubMedCentralGoogle Scholar
  100. Rebbeck TR, Friebel T et al (2005) Effect of short-term hormone replacement therapy on breast cancer risk reduction after bilateral prophylactic oophorectomy in BRCA1 and BRCA2 carriers: the PROSE Study Group. J Clin Oncol 23(31):7804–7810PubMedCrossRefPubMedCentralGoogle Scholar
  101. Reid S et al (2007) Biallelic mutations in PALB2 cause Fanconi anemia subtype FA-N and predispose to childhood cancer. Nat Genet 39(2):162–164PubMedCrossRefPubMedCentralGoogle Scholar
  102. Richards S et al (2015) Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology. Genet Med 17(5):405–424PubMedPubMedCentralCrossRefGoogle Scholar
  103. Risch HA, McLaughlin JR et al (2001) Prevalence and penetrance of germline BRCA1 and BRCA2 mutations in a population series of 649 women with ovarian cancer. Am J Hum Genet 68(3):700–710PubMedPubMedCentralCrossRefGoogle Scholar
  104. Roberts NJ et al (2012) ATM mutations in patients with hereditary pancreatic cancer. Cancer Discov 2(1):41–46PubMedCrossRefPubMedCentralGoogle Scholar
  105. Robson ME et al (2015) American Society of Clinical Oncology policy statement update: Genetic and genomic testing for cancer susceptibility. J Clin Oncol 33:3660–3667PubMedCrossRefPubMedCentralGoogle Scholar
  106. Rumilla K, Schowalter KV et al (2011) Frequency of deletions of EPCAM (TACSTD1) in MSH2 associated Lynch syndrome. J Mol Diagn 13:93–99PubMedPubMedCentralCrossRefGoogle Scholar
  107. Saslow D et al (2007) American Cancer Society guidelines for breast screening with MRI as an adjunct to mammography. CA Cancer J Clin 57(2):75–89PubMedCrossRefPubMedCentralGoogle Scholar
  108. Savitsky K, Sfez S et al (1995) The complete sequence of the coding region of the ATM gene reveals similarity to cell cycle regulators in different species. Hum Mol Genet 4(11):2025–2032PubMedCrossRefPubMedCentralGoogle Scholar
  109. Schmeler KM et al (2006) Prophylactic surgery to reduce the risk of gynecologic cancers in the Lynch syndrome. N Engl J Med 354(3):261–269PubMedCrossRefPubMedCentralGoogle Scholar
  110. Schmidt MK et al (2007) Breast cancer survival and tumor characteristics in premenopausal women carrying the CHEK2*1100delC germline mutation. J Clin Oncol 25:64–69PubMedCrossRefPubMedCentralGoogle Scholar
  111. Schneider K (2001) Counseling about cancer: strategies for genetic counseling. Wiley-Liss, New YorkGoogle Scholar
  112. Schrag D, Kuntz KM et al (1997) Decision analysis—effects of prophylactic mastectomy and oophorectomy on life expectancy among women with BRCA1 or BRCA2 mutations. N Engl J Med 336(20):1465–1471PubMedCrossRefPubMedCentralGoogle Scholar
  113. Senter L et al (2008) The clinical phenotype of Lynch syndrome due to germ-line PMS2 mutations. Gastroenterology 135(2):419–428PubMedPubMedCentralCrossRefGoogle Scholar
  114. Shattuck-Eidens D, Oliphant A et al (1997) BRCA1 sequence analysis in women at high risk for susceptibility mutations. Risk factor analysis and implications for genetic testing. JAMA 278(15):1242–1250PubMedCrossRefPubMedCentralGoogle Scholar
  115. Solomon C, Burt RW (2004) Familial adenomatous polyposis. In: GeneReviews., University of Washington. Accessed 2 Apr 2004
  116. Struewing JP, Hartge P et al (1997) The risk of cancer associated with specific mutations of BRCA1 and BRCA2 among Ashkenazi Jews. N Engl J Med 336(20):1401–1408PubMedCrossRefPubMedCentralGoogle Scholar
  117. Susswein LR et al (2016) Pathogenic and likely pathogenic variant prevalence among the first 10,000 patients referred for next-generation cancer panel testing. Genet Med 18(8):823–832PubMedCrossRefPubMedCentralGoogle Scholar
  118. Swift M, Morrell D et al (1991) Incidence of cancer in 161 families affected by ataxia-telangiectasia. N Engl J Med 325(26):1831–1836PubMedCrossRefPubMedCentralGoogle Scholar
  119. Tabori U et al (2017) Clinical management and tumor surveillance recommendations of inherited mismatch repair deficiency in childhood. Clin Cancer Res 23(1):e32–e37PubMedCrossRefPubMedCentralGoogle Scholar
  120. Tan MH et al (2012) Lifetime cancer risks in individuals with germline PTEN mutations. Clin Cancer Res 18(2):400–407PubMedPubMedCentralCrossRefGoogle Scholar
  121. The Breast Cancer Linkage Consortium (1999) Cancer risks in BRCA2 mutation carriers. J Natl Cancer Inst 91(15):1310–1316CrossRefGoogle Scholar
  122. Thull DL, Vogel VG (2004) Recognition and management of hereditary breast cancer syndromes. Oncologist 9(1):13–24PubMedCrossRefPubMedCentralGoogle Scholar
  123. Tinat J, Bouregard G et al (2009) 2009 version of the Chompret criteria for Li Fraumeni syndrome. J Clin Oncol 27:e108–e109PubMedCrossRefPubMedCentralGoogle Scholar
  124. Tirkkonen M, Johannsson O et al (1997) Distinct somatic genetic changes associated with tumor progression in carriers of BRCA1 and BRCA2 germ-line mutations. Cancer Res 57(7):1222–1227PubMedPubMedCentralGoogle Scholar
  125. Tonin P, Weber B et al (1996) Frequency of recurrent BRCA1 and BRCA2 mutations in Ashkenazi Jewish breast cancer families. Nat Med 2(11):1179–1183PubMedCrossRefPubMedCentralGoogle Scholar
  126. Tung N et al (2016) Frequency of germline mutations in 25 cancer susceptibility genes in a sequential series of patients with breast cancer. J Clin Oncol 34913:1460–1468CrossRefGoogle Scholar
  127. Turner NC, Reis-Filho JS (2006) Basal-like breast cancer and the BRCA1 phenotype. Oncogene 25:5846–5853PubMedCrossRefPubMedCentralGoogle Scholar
  128. Tyrer J, Duffy SW, Cuzick J (2004) A breast cancer prediction model incorporating familial and personal risk factors. Stat Med 23(7):1111–1130PubMedCrossRefPubMedCentralGoogle Scholar
  129. Umar A, Boland CR et al (2004) Revised Bethesda Guidelines for hereditary nonpolyposis colorectal cancer (Lynch syndrome) and microsatellite instability. J Natl Cancer Inst 96(4):261–268PubMedPubMedCentralCrossRefGoogle Scholar
  130. Varley JM et al (1999) Are there low-penetrance TP53 alleles? Evidence from childhood adrenocortical tumors. Am J Hum Genet 65(4):995–1006PubMedPubMedCentralCrossRefGoogle Scholar
  131. Vasen HF, van Ballegooijen M et al (1998) A cost-effectiveness analysis of colorectal screening of hereditary nonpolyposis colorectal carcinoma gene carriers. Cancer 82(9):1632–1637PubMedCrossRefPubMedCentralGoogle Scholar
  132. Vogel VG, Costantino JP et al (2006) Effects of tamoxifen vs. raloxifene on the risk of developing invasive breast cancer and other disease outcomes: the NSABP Study of Tamoxifen and Raloxifene (STAR) P-2 trial. JAMA 295(23):2727–2741PubMedPubMedCentralCrossRefGoogle Scholar
  133. Walsh T et al (2006) Spectrum of mutations in BRCA1, BRCA2, CHEK2, and TP53 in families at high risk of breast cancer. JAMA 295:1379–1388PubMedCrossRefPubMedCentralGoogle Scholar
  134. Walsh T et al (2011) Mutations in 12 genes for inherited ovarian, fallopian tube, and peritoneal carcinoma identified by massively parallel sequencing. Proc Natl Acad Sci U S A 108(44):18032–18037PubMedPubMedCentralCrossRefGoogle Scholar
  135. Warner E, Plewes DB et al (2004) Surveillance of BRCA1 and BRCA2 mutation carriers with magnetic resonance imaging, ultrasound, mammography, and clinical breast examination. JAMA 292(11):1317–1325PubMedCrossRefPubMedCentralGoogle Scholar
  136. Watanabe T, Wu TT et al (2001) Molecular predictors of survival after adjuvant chemotherapy for colon cancer. N Engl J Med 344(16):1196–1206PubMedPubMedCentralCrossRefGoogle Scholar
  137. Weber T (1996) Clinical surveillance recommendations adopted for HNPCC. Lancet 348:465CrossRefGoogle Scholar
  138. Weischer M, Bojesen SE, Tybjaerg-Hansen A, Axelsson CK, Nordestgaard BG (2007) Increased risk of breast cancer associated with CHEK2*1100delC germline mutation. J Clin Oncol 25:64–69Google Scholar
  139. Wijnen JT, Vasen HF et al (1998) Clinical findings with implications for genetic testing in families with clustering of colorectal cancer. N Engl J Med 339(8):511–518PubMedCrossRefPubMedCentralGoogle Scholar
  140. Wimmer K, Kratz CP (2010) Constitutional mismatch repair-deficiency syndrome. Haematologica 95(5):699–701PubMedPubMedCentralCrossRefGoogle Scholar
  141. Win AK et al (2014) Risk of colorectal cancer for carriers of mutations in MUTYH, with and without a family history of cancer. Gastroenterology 146:2256–2262CrossRefGoogle Scholar
  142. Wooster R, Bignell G et al (1995) Identification of the breast-cancer susceptibility gene BRCA2. Nature 378(6559):789–792PubMedCrossRefPubMedCentralGoogle Scholar
  143. Xia B et al (2006) Control of BRCA2 cellular and clinical functions by a nuclear partner, PALB2. Mol Cell 22(6):719–729PubMedPubMedCentralCrossRefGoogle Scholar
  144. Yang S et al (2017) Sources of discordance among germ-line variant classifications in ClinVar. Genet Med 19(10):1118–1126PubMedPubMedCentralCrossRefGoogle Scholar

Copyright information

© Springer Nature Switzerland AG 2019

Authors and Affiliations

  1. 1.Division of Human Genetics, Department of MedicineThe Ohio State University Comprehensive Cancer CenterColumbusUSA
  2. 2.Division of Medical Oncology, Department of MedicineThe Ohio State University Comprehensive Cancer CenterColumbusUSA

Personalised recommendations