Advertisement

Journal of Genetic Counseling

, Volume 27, Issue 5, pp 1187–1199 | Cite as

A Clinical Decision Support Tool to Predict Cancer Risk for Commonly Tested Cancer-Related Germline Mutations

  • Danielle Braun
  • Jiabei Yang
  • Molly Griffin
  • Giovanni Parmigiani
  • Kevin S. Hughes
Original Research

Abstract

The rapid drop in the cost of DNA sequencing led to the availability of multi-gene panels, which test 25 or more cancer susceptibility genes for a low cost. Clinicians and genetic counselors need a tool to interpret results, understand risk of various cancers, and advise on a management strategy. This is challenging as there are multiple studies regarding each gene, and it is not possible for clinicians and genetic counselors to be aware of all publications, nor to appreciate the relative accuracy and importance of each. Through an extensive literature review, we have identified reliable studies and derived estimates of absolute risk. We have also developed a systematic mechanism and informatics tools for (1) data curation, (2) the evaluation of quality of studies, and (3) the statistical analysis necessary to obtain risk. We produced the risk prediction clinical decision support tool ASK2ME (All Syndromes Known to Man Evaluator). It provides absolute cancer risk predictions for various hereditary cancer susceptibility genes. These predictions are specific to patients’ gene carrier status, age, and history of relevant prophylactic surgery. By allowing clinicians to enter patient information and receive patient-specific cancer risks, this tool aims to have a significant impact on the quality of precision cancer prevention and disease management activities relying on panel testing. It is important to note that this tool is dynamic and constantly being updated, and currently, some of its limitations include (1) for many gene-cancer associations risk estimates are based on one study rather than meta-analysis, (2) strong assumptions on prior cancers, (3) lack of uncertainty measures, and (4) risk estimates for a growing set of gene-cancer associations which are not always variant specific. All of these concerns are being addressed on an ongoing basis, aiming to make the tool even more accurate.

Keywords

Germline mutation Disease susceptibility Genetic predisposition to disease Risk assessment Risk management 

Notes

Acknowledgements

We gratefully acknowledge support from the National Cancer Institute at the National Institutes of Health [4P30CA006516-51] which supported Dr. Parmigiani.

Compliance with Ethical Standards

Conflict of Interest

Dr. Hughes receives Honoraria from Myriad Genetics Veritas Genetics, Advisory Board for Beacon (An RFID Biopsy Marker), and is a founder of and has a financial interest in Hughes Risk Apps, LLC. Dr. Hughes’s interests were reviewed and are managed by Massachusetts General Hospital and Partners Health Care in accordance with their conflict of interest policies.

Dr. Parmigiani is a member of the Scientific Advisory Board and has a financial interest in Cancer Risk Apps LLC (CRA). CRA commercializes software for management of patients at high risk of cancer. At the present time, CRA is not supporting or licensing ask2me. We feel there is no significant overlap with this work.

Dr. Braun, Ms. Yang, and Ms. Griffin declare that they have no conflict of interest.

Human Studies and Informed Consent

This article does not contain human subjects.

Animal Studies

No animal studies were carried out by the authors for this article.

Supplementary material

10897_2018_238_MOESM1_ESM.docx (50 kb)
ESM 1 (DOCX 50 kb)

References

  1. Antoniou, A. C., Casadei, S., Heikkinen, T., Barrowdale, D., Pylkäs, K., Roberts, J., Lee, A., Subramanian, D., de Leeneer, K., Fostira, F., Tomiak, E., Neuhausen, S. L., Teo, Z. L., Khan, S., Aittomäki, K., Moilanen, J. S., Turnbull, C., Seal, S., Mannermaa, A., Kallioniemi, A., Lindeman, G. J., Buys, S. S., Andrulis, I. L., Radice, P., Tondini, C., Manoukian, S., Toland, A. E., Miron, P., Weitzel, J. N., Domchek, S. M., Poppe, B., Claes, K. B. M., Yannoukakos, D., Concannon, P., Bernstein, J. L., James, P. A., Easton, D. F., Goldgar, D. E., Hopper, J. L., Rahman, N., Peterlongo, P., Nevanlinna, H., King, M. C., Couch, F. J., Southey, M. C., Winqvist, R., Foulkes, W. D., & Tischkowitz, M. (2014). Breast-cancer risk in families with mutations in PALB2. New England Journal of Medicine, 371(6), 497–506.CrossRefGoogle Scholar
  2. Barrow, E., Robinson, L., Alduaij, W., Shenton, A., Clancy, T., Lalloo, F., Hill, J., & Evans, D. G. (2009). Cumulative lifetime incidence of extracolonic cancers in lynch syndrome: A report of 121 families with proven mutations. Clinical Genetics, 75(2), 141–149.CrossRefGoogle Scholar
  3. Bonadona, V., Bonaïti, B., Olschwang, S., Grandjouan, S., Huiart, L., Longy, M., Guimbaud, R., Buecher, B., Bignon, Y. J., Caron, O., Colas, C., Noguès, C., Lejeune-Dumoulin, S., Olivier-Faivre, L., Polycarpe-Osaer, F., Nguyen, T. D., Desseigne, F., Saurin, J. C., Berthet, P., Leroux, D., Duffour, J., Manouvrier, S., Frébourg, T., Sobol, H., Lasset, C., Bonaïti-Pellié, C., & French Cancer Genetics Network. (2011). Cancer risks associated with germline mutations in MLH1, MSH2, and MSH6 genes in Lynch syndrome. JAMA, 305(22), 2304–2310.CrossRefGoogle Scholar
  4. Brewer, N. T., Richman, A. R., DeFrank, J. T., Reyna, V. F., & Carey, L. A. (2012). Improving communication of breast cancer recurrence risk. Breast Cancer Research and Treatment, 133(2), 553–561.CrossRefGoogle Scholar
  5. Chen, S., & Parmigiani, G. (2007). Meta-analysis of BRCA1 and BRCA2 penetrance. Journal of Clinical Oncology, 25(11), 1329–1333.CrossRefGoogle Scholar
  6. Couch, F. J., Hart, S. N., Sharma, P., Toland, A. E., Wang, X., Miron, P., Olson, J. E., Godwin, A. K., Pankratz, V. S., Olswold, C., Slettedahl, S., Hallberg, E., Guidugli, L., Davila, J. I., Beckmann, M. W., Janni, W., Rack, B., Ekici, A. B., Slamon, D. J., Konstantopoulou, I., Fostira, F., Vratimos, A., Fountzilas, G., Pelttari, L. M., Tapper, W. J., Durcan, L., Cross, S. S., Pilarski, R., Shapiro, C. L., Klemp, J., Yao, S., Garber, J., Cox, A., Brauch, H., Ambrosone, C., Nevanlinna, H., Yannoukakos, D., Slager, S. L., Vachon, C. M., Eccles, D. M., & Fasching, P. A. (2014). Inherited mutations in 17 breast cancer susceptibility genes among a large triple-negative breast cancer cohort unselected for family history of breast cancer. Journal of Clinical Oncology, 33(4), 304–311.CrossRefGoogle Scholar
  7. Cybulski, C., Wokołorczyk, D., Kładny, J., Kurzwaski, G., Suchy, J., Grabowska, E., Gronwald, J., Huzarski, T., Byrski, T., Górski, B., Dȩbniak, T., Narod, S. A., & Lubiński, J. (2007). Germline CHEK2 mutations and colorectal cancer risk: Different effects of a missense and truncating mutations? European Journal of Human Genetics, 15(2), 237–241.CrossRefGoogle Scholar
  8. Cybulski, C., Wokołorczyk, D., Kluźniak, W., Jakubowska, A., Górski, B., Gronwald, J., et al. (2013). An inherited NBN mutation is associated with poor prognosis prostate cancer. British Journal of Cancer, 108(2), 461–468.CrossRefGoogle Scholar
  9. Davies, K. R., Cantor, S. B., & Brewster, A. M. (2015). Better contralateral breast cancer risk estimation and alternative options to contralateral prophylactic mastectomy. International Journal of Women's Health, 7, 181.PubMedPubMedCentralGoogle Scholar
  10. de Snoo, F. A., Bishop, D. T., Bergman, W., van Leeuwen, I., van der Drift, C., van Nieuwpoort, F. A., Out-Luiting, C. J., Vasen, H. F., ter Huurne, J. A. C., Frants, R. R., Willemze, R., Breuning, M. H., & Gruis, N. A. (2008). Increased risk of cancer other than melanoma in CDKN2A founder mutation (p16-Leiden)-positive melanoma families. Clinical Cancer Research, 14(21), 7151–7157.CrossRefGoogle Scholar
  11. Desmond, A., Kurian, A. W., Gabree, M., Mills, M. A., Anderson, M. J., Kobayashi, Y., Horick, N., Yang, S., Shannon, K. M., Tung, N., Ford, J. M., Lincoln, S. E., & Ellisen, L. W. (2015). Clinical actionability of multigene panel testing for hereditary breast and ovarian cancer risk assessment. JAMA Oncology, 1(7), 943–951.CrossRefGoogle Scholar
  12. Domchek, S. M., Friebel, T. M., Singer, C. F., Evans, D. G., Lynch, H. T., Isaacs, C., Garber, J. E., Neuhausen, S. L., Matloff, E., Eeles, R., Pichert, G., van t'veer, L., Tung, N., Weitzel, J. N., Couch, F. J., Rubinstein, W. S., Ganz, P. A., Daly, M. B., Olopade, O. I., Tomlinson, G., Schildkraut, J., Blum, J. L., & Rebbeck, T. R. (2010). Association of risk-reducing surgery in BRCA1 or BRCA2 mutation carriers with cancer risk and mortality. JAMA, 304(9), 967–975.CrossRefGoogle Scholar
  13. Dowty, J. G., Win, A. K., Buchanan, D. D., Lindor, N. M., Macrae, F. A., Clendenning, M., Antill, Y. C., Thibodeau, S. N., Casey, G., Gallinger, S., Marchand, L. L., Newcomb, P. A., Haile, R. W., Young, G. P., James, P. A., Giles, G. G., Gunawardena, S. R., Leggett, B. A., Gattas, M., Boussioutas, A., Ahnen, D. J., Baron, J. A., Parry, S., Goldblatt, J., Young, J. P., Hopper, J. L., & Jenkins, M. A. (2013). Cancer risks for MLH1 and MSH2 mutation carriers. Human Mutation, 34(3), 490–497.CrossRefGoogle Scholar
  14. Engel, C., Loeffler, M., Steinke, V., Rahner, N., Holinski-Feder, E., Dietmaier, W., Schackert, H. K., Goergens, H., von Knebel Doeberitz, M., Goecke, T. O., Schmiegel, W., Buettner, R., Moeslein, G., Letteboer, T. G. W., García, E. G., Hes, F. J., Hoogerbrugge, N., Menko, F. H., van Os, T. A. M., Sijmons, R. H., Wagner, A., Kluijt, I., Propping, P., & Vasen, H. F. A. (2012). Risks of less common cancers in proven mutation carriers with lynch syndrome. Journal of Clinical Oncology, 30(35), 4409–4415.CrossRefGoogle Scholar
  15. Graffeo, R., Livraghi, L., Pagani, O., Goldhirsch, A., Partridge, A.H., & Garber, J.E. (2016). Time to incorporate germline multigene panel testing into breast and ovarian cancer patient care. Breast Cancer Research and Treatment, 1–18.Google Scholar
  16. Groden, J., Thliveris, A., Samowitz, W., Carlson, M., Gelbert, L., Albertsen, H., Joslyn, G., Stevens, J., Spirio, L., Robertson, M., Sargeant, L., Krapcho, K., Wolff, E., Burt, R., Hughes, J. P., Warrington, J., McPherson, J., Wasmuth, J., le Paslier, D., Abderrahim, H., Cohen, D., Leppert, M., & White, R. (1991). Identification and characterization of the familial adenomatous polyposis coli gene. Cell, 66(3), 589–600.CrossRefGoogle Scholar
  17. Haidich, A. B. (2010). Meta-analysis in medical research. Hippokratia, 14(Suppl 1), 29–37.PubMedPubMedCentralGoogle Scholar
  18. Hanoch, Y., Miron-Shatz, T., Rolison, J. J., Omer, Z., & Ozanne, E. (2015). Shared decision making in patients at risk of cancer: The role of domain and numeracy. Health Expectations, 18(6), 2799–2810.CrossRefGoogle Scholar
  19. Hansford, S., Kaurah, P., Li-Chang, H., Woo, M., Senz, J., Pinheiro, H., Schrader, K. A., Schaeffer, D. F., Shumansky, K., Zogopoulos, G., Santos, T. A., Claro, I., Carvalho, J., Nielsen, C., Padilla, S., Lum, A., Talhouk, A., Baker-Lange, K., Richardson, S., Lewis, I., Lindor, N. M., Pennell, E., MacMillan, A., Fernandez, B., Keller, G., Lynch, H., Shah, S. P., Guilford, P., Gallinger, S., Corso, G., Roviello, F., Caldas, C., Oliveira, C., Pharoah, P. D. P., & Huntsman, D. G. (2015). Hereditary diffuse gastric cancer syndrome: CDH1 mutations and beyond. JAMA Oncology, 1(1), 23–32.CrossRefGoogle Scholar
  20. Helgason, H., Rafnar, T., Olafsdottir, H. S., Jonasson, J. G., Sigurdsson, A., Stacey, S. N., Jonasdottir, A., Tryggvadottir, L., Alexiusdottir, K., Haraldsson, A., le Roux, L., Gudmundsson, J., Johannsdottir, H., Oddsson, A., Gylfason, A., Magnusson, O. T., Masson, G., Jonsson, T., Skuladottir, H., Gudbjartsson, D. F., Thorsteinsdottir, U., Sulem, P., & Stefansson, K. (2015). Loss-of-function variants in ATM confer risk of gastric cancer. Nature Genetics, 47(8), 906–910.CrossRefGoogle Scholar
  21. Katki, H. A. (2007). Incorporating medical interventions into carrier probability estimation for genetic counseling. BMC Medical Genetics, 8(1), 13.CrossRefGoogle Scholar
  22. Khan, K. S., Kunz, R., Kleijnen, J., & Antes, G. (2003). Five steps to conducting a systematic review. Journal of the Royal Society of Medicine, 96(3), 118–121.CrossRefGoogle Scholar
  23. Ma, X., Zhang, B., & Zheng, W. (2013). Genetic variants associated with colorectal cancer risk: comprehensive research synopsis, meta-analysis, and epidemiological evidence. Gut, gutjnl-2012.Google Scholar
  24. Ma, I. T., Gray, R. J., Wasif, N., Butler, K. A., Cornella, J. L., Magrina, J. F., Magtibay, P. M., Casey, W. J., Mahabir, R., Rebecca, A. M., Hunt, K. S., & Pockaj, B. A. (2017). Outcomes of concurrent breast and gynecologic risk reduction surgery. Annals of Surgical Oncology, 24(1), 77–83.CrossRefGoogle Scholar
  25. Mai, P. L., Best, A. F., Peters, J. A., DeCastro, R. M., Khincha, P. P., Loud, J. T., Bremer, R. C., Rosenberg, P. S., & Savage, S. A. (2016). Risks of first and subsequent cancers among TP53 mutation carriers in the National Cancer Institute li-Fraumeni syndrome cohort. Cancer, 122(23), 3673–3681.CrossRefGoogle Scholar
  26. Marabelli, M., Cheng, S. C., & Parmigiani, G. (2016). Penetrance of ATM gene mutations in breast cancer: A meta-analysis of different measures of risk. Genetic Epidemiology, 40(5), 425–431.CrossRefGoogle Scholar
  27. Maxwell, K. N., Wubbenhorst, B., D’Andrea, K., Garman, B., Long, J. M., Powers, J., et al. (2014). Prevalence of mutations in a panel of breast cancer susceptibility genes in BRCA1/2-negative patients with early-onset breast cancer. Genetics in Medicine, 17(8), 630–638.CrossRefGoogle Scholar
  28. Mocci, E., Milne, R. L., Méndez-Villamil, E. Y., Hopper, J. L., John, E. M., Andrulis, I. L., et al. (2013). Risk of pancreatic cancer in breast cancer families from the breast cancer family registry. Cancer Epidemiology and Prevention Biomarkers, 22(5), 803–811.CrossRefGoogle Scholar
  29. Plichta, J. K., Griffin, M., Thakuria, J., & Hughes, K. S. (2016). What’s new in genetic testing for cancer susceptibility? Oncology, 30(9), 787–799.PubMedGoogle Scholar
  30. Portnoy, D. B., Roter, D., & Erby, L. H. (2010). The role of numeracy on client knowledge in BRCA genetic counseling. Patient Education and Counseling, 81(1), 131–136.CrossRefGoogle Scholar
  31. R Core Team (2017). R: A language for statistical computing. R Foundation for Statistical Computing, https://www.R-project.org/.
  32. Ramus, S. J., Song, H., Dicks, E., Tyrer, J. P., Rosenthal, A. N., Intermaggio, M. P., Fraser, L., Gentry-Maharaj, A., Hayward, J., Philpott, S., Anderson, C., Edlund, C. K., Conti, D., Harrington, P., Barrowdale, D., Bowtell, D. D., Alsop, K., Mitchell, G., AOCS Study Group, Cicek, M. S., Cunningham, J. M., Fridley, B. L., Alsop, J., Jimenez-Linan, M., Poblete, S., Lele, S., Sucheston-Campbell, L., Moysich, K. B., Sieh, W., McGuire, V., Lester, J., Bogdanova, N., Dürst, M., Hillemanns, P., Ovarian Cancer Association Consortium, Odunsi, K., Whittemore, A. S., Karlan, B. Y., Dörk, T., Goode, E. L., Menon, U., Jacobs, I. J., Antoniou, A. C., Pharoah, P. D., & Gayther, S. A. (2015). Germline mutations in the BRIP1, BARD1, PALB2, and NBN genes in women with ovarian cancer. JNCI: Journal of the National Cancer Institute, 107(11).Google Scholar
  33. Rebbeck, T. R., Friebel, T., Lynch, H. T., Neuhausen, S. L., van’t Veer, L., Garber, J. E., et al. (2004). Bilateral prophylactic mastectomy reduces breast cancer risk in BRCA1 and BRCA2 mutation carriers: The PROSE Study Group. Journal of Clinical Oncology, 22(6), 1055–1062.CrossRefGoogle Scholar
  34. Rebbeck, T. R., Mitra, N., Wan, F., Sinilnikova, O. M., Healey, S., McGuffog, L., Mazoyer, S., Chenevix-Trench, G., Easton, D. F., Antoniou, A. C., Nathanson, K. L., CIMBA Consortium, Laitman, Y., Kushnir, A., Paluch-Shimon, S., Berger, R., Zidan, J., Friedman, E., Ehrencrona, H., Stenmark-Askmalm, M., Einbeigi, Z., Loman, N., Harbst, K., Rantala, J., Melin, B., Huo, D., Olopade, O. I., Seldon, J., Ganz, P. A., Nussbaum, R. L., Chan, S. B., Odunsi, K., Gayther, S. A., Domchek, S. M., Arun, B. K., Lu, K. H., Mitchell, G., Karlan, B. Y., Walsh, C., Lester, J., Godwin, A. K., Pathak, H., Ross, E., Daly, M. B., Whittemore, A. S., John, E. M., Miron, A., Terry, M. B., Chung, W. K., Goldgar, D. E., Buys, S. S., Janavicius, R., Tihomirova, L., Tung, N., Dorfling, C. M., van Rensburg, E., Steele, L., Neuhausen, S. L., Ding, Y. C., Ejlertsen, B., Gerdes, A. M., Hansen Tv, Ramón y Cajal, T., Osorio, A., Benitez, J., Godino, J., Tejada, M. I., Duran, M., Weitzel, J. N., Bobolis, K. A., Sand, S. R., Fontaine, A., Savarese, A., Pasini, B., Peissel, B., Bonanni, B., Zaffaroni, D., Vignolo-Lutati, F., Scuvera, G., Giannini, G., Bernard, L., Genuardi, M., Radice, P., Dolcetti, R., Manoukian, S., Pensotti, V., Gismondi, V., Yannoukakos, D., Fostira, F., Garber, J., Torres, D., Rashid, M. U., Hamann, U., Peock, S., Frost, D., Platte, R., Evans, D. G., Eeles, R., Davidson, R., Eccles, D., Cole, T., Cook, J., Brewer, C., Hodgson, S., Morrison, P. J., Walker, L., Porteous, M. E., Kennedy, M. J., Izatt, L., Adlard, J., Donaldson, A., Ellis, S., Sharma, P., Schmutzler, R. K., Wappenschmidt, B., Becker, A., Rhiem, K., Hahnen, E., Engel, C., Meindl, A., Engert, S., Ditsch, N., Arnold, N., Plendl, H. J., Mundhenke, C., Niederacher, D., Fleisch, M., Sutter, C., Bartram, C. R., Dikow, N., Wang-Gohrke, S., Gadzicki, D., Steinemann, D., Kast, K., Beer, M., Varon-Mateeva, R., Gehrig, A., Weber, B. H., Stoppa-Lyonnet, D., Sinilnikova, O. M., Mazoyer, S., Houdayer, C., Belotti, M., Gauthier-Villars, M., Damiola, F., Boutry-Kryza, N., Lasset, C., Sobol, H., Peyrat, J. P., Muller, D., Fricker, J. P., Collonge-Rame, M. A., Mortemousque, I., Nogues, C., Rouleau, E., Isaacs, C., de Paepe, A., Poppe, B., Claes, K., de Leeneer, K., Piedmonte, M., Rodriguez, G., Wakely, K., Boggess, J., Blank, S. V., Basil, J., Azodi, M., Phillips, K. A., Caldes, T., de la Hoya, M., Romero, A., Nevanlinna, H., Aittomäki, K., van der Hout, A., Hogervorst, F. B., Verhoef, S., Collée, J. M., Seynaeve, C., Oosterwijk, J. C., Gille, J. J., Wijnen, J. T., Gómez Garcia, E. B., Kets, C. M., Ausems, M. G., Aalfs, C. M., Devilee, P., Mensenkamp, A. R., Kwong, A., Olah, E., Papp, J., Diez, O., Lazaro, C., Darder, E., Blanco, I., Salinas, M., Jakubowska, A., Lubinski, J., Gronwald, J., Jaworska-Bieniek, K., Durda, K., Sukiennicki, G., Huzarski, T., Byrski, T., Cybulski, C., Toloczko-Grabarek, A., Złowocka-Perłowska, E., Menkiszak, J., Arason, A., Barkardottir, R. B., Simard, J., Laframboise, R., Montagna, M., Agata, S., Alducci, E., Peixoto, A., Teixeira, M. R., Spurdle, A. B., Lee, M. H., Park, S. K., Kim, S. W., Friebel, T. M., Couch, F. J., Lindor, N. M., Pankratz, V. S., Guidugli, L., Wang, X., Tischkowitz, M., Foretova, L., Vijai, J., Offit, K., Robson, M., Rau-Murthy, R., Kauff, N., Fink-Retter, A., Singer, C. F., Rappaport, C., Gschwantler-Kaulich, D., Pfeiler, G., Tea, M. K., Berger, A., Greene, M. H., Mai, P. L., Imyanitov, E. N., Toland, A. E., Senter, L., Bojesen, A., Pedersen, I. S., Skytte, A. B., Sunde, L., Thomassen, M., Moeller, S. T., Kruse, T. A., Jensen, U. B., Caligo, M. A., Aretini, P., Teo, S. H., Selkirk, C. G., Hulick, P. J., & Andrulis, I. (2015). Association of type and location of BRCA1 and BRCA2 mutations with risk of breast and ovarian cancer. JAMA, 313(13), 1347–1361.CrossRefGoogle Scholar
  35. Rendle, K. A., Halley, M. C., May, S. G., & Frosch, D. L. (2015). Redefining risk and benefit: Understanding the decision to undergo contralateral prophylactic mastectomy. Qualitative Health Research, 25(9), 1251–1259.CrossRefGoogle Scholar
  36. Resta, N., Pierannunzio, D., Lenato, G. M., Stella, A., Capocaccia, R., Bagnulo, R., Lastella, P., Susca, F. C., Bozzao, C., Loconte, D. C., Sabbà, C., Urso, E., Sala, P., Fornasarig, M., Grammatico, P., Piepoli, A., Host, C., Turchetti, D., Viel, A., Memo, L., Giunti, L., Stigliano, V., Varesco, L., Bertario, L., Genuardi, M., Lucci Cordisco, E., Tibiletti, M. G., di Gregorio, C., Andriulli, A., Ponz de Leon, M., & AIFEG. (2013). Cancer risk associated with STK11/LKB1 germline mutations in Peutz–Jeghers syndrome patients: Results of an Italian multicenter study. Digestive and Liver Disease, 45(7), 606–611.CrossRefGoogle Scholar
  37. Riley, B. D., Culver, J. O., Skrzynia, C., Senter, L. A., Peters, J. A., Costalas, J. W., Callif-Daley, F., Grumet, S. C., Hunt, K. S., Nagy, R. S., McKinnon, W. C., Petrucelli, N. M., Bennett, R. L., & Trepanier, A. M. (2012). Essential elements of genetic cancer risk assessment, counseling, and testing: Updated recommendations of the National Society of Genetic Counselors. Journal of Genetic Counseling, 21(2), 151–161.CrossRefGoogle Scholar
  38. Roed Nielsen, H., Petersen, J., Therkildsen, C., Skytte, A. B., & Nilbert, M. (2016). Increased risk of male cancer and identification of a potential prostate cancer cluster region in BRCA2. Acta Oncologica, 55(1), 38–44.CrossRefGoogle Scholar
  39. Schmidt, M. K., Hogervorst, F., Van Hien, R., Cornelissen, S., Broeks, A., Adank, M. A., et al. (2016). Age-and tumor subtype–specific breast cancer risk estimates for CHEK2* 1100delC carriers. Journal of Clinical Oncology, 34(23), 2750–2760.CrossRefGoogle Scholar
  40. Sim, I., Gorman, P., Greenes, R. A., Haynes, R. B., Kaplan, B., Lehmann, H., & Tang, P. C. (2001). Clinical decision support systems for the practice of evidence-based medicine. Journal of the American Medical Informatics Association, 8(6), 527–534.CrossRefGoogle Scholar
  41. Song, H., Dicks, E., Ramus, S. J., Tyrer, J. P., Intermaggio, M. P., Hayward, J., Edlund, C. K., Conti, D., Harrington, P., Fraser, L., Philpott, S., Anderson, C., Rosenthal, A., Gentry-Maharaj, A., Bowtell, D. D., Alsop, K., Cicek, M. S., Cunningham, J. M., Fridley, B. L., Alsop, J., Jimenez-Linan, M., Høgdall, E., Høgdall, C. K., Jensen, A., Kjaer, S. K., Lubiński, J., Huzarski, T., Jakubowska, A., Gronwald, J., Poblete, S., Lele, S., Sucheston-Campbell, L., Moysich, K. B., Odunsi, K., Goode, E. L., Menon, U., Jacobs, I. J., Gayther, S. A., & Pharoah, P. D. P. (2015). Contribution of germline mutations in the RAD51B, RAD51C, and RAD51D genes to ovarian cancer in the population. Journal of Clinical Oncology, 33(26), 2901–2907.CrossRefGoogle Scholar
  42. Strande, N.T., Riggs, E.R., Buchanan, A.H., Ceyhan-Birsoy, O., DiStefano, M., Dwight, S.S., et al. (2017). Evaluating the clinical validity of gene-disease associations: an evidence-based framework developed by the Clinical Genome Resource. The American Journal of Human Genetics.Google Scholar
  43. Tan, M. H., Mester, J. L., Ngeow, J., Rybicki, L. A., Orloff, M. S., & Eng, C. (2012). Lifetime cancer risks in individuals with germline PTEN mutations. Clinical Cancer Research, 18(2), 400–407.CrossRefGoogle Scholar
  44. Ten Broeke, S. W., Brohet, R. M., Tops, C. M., van der Klift, H. M., Velthuizen, M. E., Bernstein, I., et al. (2014). Lynch syndrome caused by germline PMS2 mutations: Delineating the cancer risk. Journal of Clinical Oncology, 33(4), 319–325.CrossRefGoogle Scholar
  45. Theodoratou, E., Campbell, H., Tenesa, A., Houlston, R., Webb, E., Lubbe, S., Broderick, P., Gallinger, S., Croitoru, E. M., Jenkins, M. A., Win, A. K., Cleary, S. P., Koessler, T., Pharoah, P. D., Küry, S., Bézieau, S., Buecher, B., Ellis, N. A., Peterlongo, P., Offit, K., Aaltonen, L. A., Enholm, S., Lindblom, A., Zhou, X. L., Tomlinson, I. P., Moreno, V., Blanco, I., Capellà, G., Barnetson, R., Porteous, M. E., Dunlop, M. G., & Farrington, S. M. (2010). A large-scale meta-analysis to refine colorectal cancer risk estimates associated with MUTYH variants. British Journal of Cancer, 103(12), 1875–1884.CrossRefGoogle Scholar
  46. Thompson, D., Easton, D., & Breast Cancer Linkage Consortium. (2001). Variation in cancer risks, by mutation position, in BRCA2 mutation carriers. The American Journal of Human Genetics, 68(2), 410–419.CrossRefGoogle Scholar
  47. Trialists' Group, A. T. A. C. (2005). Results of the ATAC (arimidex, tamoxifen, alone or in combination) trial after completion of 5 years’ adjuvant treatment for breast cancer. The Lancet, 365(9453), 60–62.CrossRefGoogle Scholar
  48. Tung, N., Battelli, C., Allen, B., Kaldate, R., Bhatnagar, S., Bowles, K., Timms, K., Garber, J. E., Herold, C., Ellisen, L., Krejdovsky, J., DeLeonardis, K., Sedgwick, K., Soltis, K., Roa, B., Wenstrup, R. J., & Hartman, A. R. (2015). Frequency of mutations in individuals with breast cancer referred for BRCA1 and BRCA2 testing using next-generation sequencing with a 25-gene panel. Cancer, 121(1), 25–33.CrossRefGoogle Scholar
  49. Tung, N., Domchek, S. M., Stadler, Z., Nathanson, K. L., Couch, F., Garber, J. E., Offit, K., & Robson, M. E. (2016a). Counselling framework for moderate-penetrance cancer-susceptibility mutations. Nature Reviews Clinical Oncology, 13(9), 581–588.CrossRefGoogle Scholar
  50. Tung, N., Lin, N. U., Kidd, J., Allen, B. A., Singh, N., Wenstrup, R. J., Hartman, A. R., Winer, E. P., & Garber, J. E. (2016b). Frequency of germline mutations in 25 cancer susceptibility genes in a sequential series of patients with breast cancer. Journal of Clinical Oncology, 34(13), 1460–1468.CrossRefGoogle Scholar
  51. Van Lier, M. G. F., Wagner, A., Mathus-Vliegen, E. M. H., Kuipers, E. J., Steyerberg, E. W., & Van Leerdam, M. E. (2010). High cancer risk in Peutz–Jeghers syndrome: A systematic review and surveillance recommendations. The American Journal of Gastroenterology, 105(6), 1258–1264.CrossRefGoogle Scholar
  52. Walsh, T., Casadei, S., Lee, M. K., Pennil, C. C., Nord, A. S., Thornton, A. M., Roeb, W., Agnew, K. J., Stray, S. M., Wickramanayake, A., Norquist, B., Pennington, K. P., Garcia, R. L., King, M. C., & Swisher, E. M. (2011). Mutations in 12 genes for inherited ovarian, fallopian tube, and peritoneal carcinoma identified by massively parallel sequencing. Proceedings of the National Academy of Sciences, 108(44), 18032–18037.CrossRefGoogle Scholar
  53. Wang, Y., Dai, B., & Ye, D. (2015). CHEK2 mutation and risk of prostate cancer: A systematic review and meta-analysis. International Journal of Clinical and Experimental Medicine, 8(9), 15708–15715.PubMedPubMedCentralGoogle Scholar
  54. Win, A. K., Reece, J. C., Dowty, J. G., Buchanan, D. D., Clendenning, M., Rosty, C., Southey, M. C., Young, J. P., Cleary, S. P., Kim, H., Cotterchio, M., Macrae, F. A., Tucker, K. M., Baron, J. A., Burnett, T., le Marchand, L., Casey, G., Haile, R. W., Newcomb, P. A., Thibodeau, S. N., Hopper, J. L., Gallinger, S., Winship, I. M., Lindor, N. M., & Jenkins, M. A. (2016). Risk of extracolonic cancers for people with biallelic and monoallelic mutations in MUTYH. International Journal of Cancer, 139(7), 1557–1563.CrossRefGoogle Scholar
  55. Zhang, Z. H., Yang, L. S., Huang, F., Hao, J. H., Su, P. Y., & Sun, Y. H. (2012). Current evidence on the relationship between two polymorphisms in the NBS1 gene and breast cancer risk: A meta-analysis. Asian Pacific Journal of Cancer Prevention, 13(11), 5375–5379.CrossRefGoogle Scholar

Copyright information

© National Society of Genetic Counselors, Inc. 2018

Authors and Affiliations

  1. 1.Department of BiostatisticsHarvard T.H. Chan School of Public HealthBostonUSA
  2. 2.Department of Biostatistics and Computational BiologyDana-Farber Cancer InstituteBostonUSA
  3. 3.Division of Surgical OncologyMassachusetts General HospitalBostonUSA
  4. 4.Surgery, Harvard Medical SchoolBostonUSA

Personalised recommendations