Cascade Genetic Testing for Lynch Syndrome: Current Understanding, Challenges, and Emerging Opportunities
Main Article Content
Abstract
Cascade genetic testing, a highly effective method of identifying high penetrance cancer risk mutations in the family, is a promising method of prevention. Cascade testing is defined as directed genetic testing of at-risk relatives of individuals known to have actionable mutations However, it is tremendously underutilized in clinical practice, and the reasons are complex and diverse. We discuss these reasons and consider areas of research for key findings, strengths and weaknesses. We offer testable solutions for increasing interest and use of cascade testing opportunities in families and in clinical practice using colorectal cancer as an example. This area of clinical research has great potential to save lives by improving cancer prevention and early detection in families at high genetic risk, and should be actively pursued with resources and ideas.
Keywords:
Cascade testing, population testing, cancer risk, genetic risk
Article Details
How to Cite
BOWEN, Deborah J; DUSIC, EJ; MAKHNOON, Sukh.
Cascade Genetic Testing for Lynch Syndrome: Current Understanding, Challenges, and Emerging Opportunities.
Medical Research Archives, [S.l.], v. 10, n. 2, feb. 2022.
ISSN 2375-1924.
Available at: <https://esmed.org/MRA/mra/article/view/2629>. Date accessed: 25 apr. 2024.
doi: https://doi.org/10.18103/mra.v10i2.2629.
Section
Research Articles
The Medical Research Archives grants authors the right to publish and reproduce the unrevised contribution in whole or in part at any time and in any form for any scholarly non-commercial purpose with the condition that all publications of the contribution include a full citation to the journal as published by the Medical Research Archives.
References
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5. Wolf SM, Branum R, Koenig BA, et al. Returning a Research Participant’s Genomic Results to Relatives: Analysis and Recommendations. J Law Med Ethics. 2015;43(3):440-463.
6. Krawczak M, Cooper DN, Schmidtke J. Estimating the efficacy and efficiency of cascade genetic screening. Am J Hum Genet. 2001;69(2):361-370.
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9. Winawer SJ, Krabshuis J, Lambert R, OʼBrien M, Fried M. Cascade Colorectal Cancer Screening Guidelines: A Global Conceptual Model. Journal of Clinical Gastroenterology. 2011;45(4):297-300.
10. Accessed May 25, 2017. https://www.cdc.gov/genomics/gtesting/egapp/recommend/lynch.htm
11. Ponz de Leon M, Benatti P, Di Gregorio C, et al. Genetic testing among high-risk individuals in families with hereditary nonpolyposis colorectal cancer. British Journal of Cancer. 2004;90(4):882-887.
12. Aktan-Collan K, Haukkala A, Pylvänäinen K, et al. Direct contact in inviting high-risk members of hereditary colon cancer families to genetic counselling and DNA testing. J Med Genet. 2007;44(11):732-738.
13. Hadley DW, Jenkins J, Dimond E, et al. Genetic counseling and testing in families with hereditary nonpolyposis colorectal cancer. Arch Intern Med. 2003;163(5):573-582.
14. Ramsoekh D, van Leerdam ME, Tops CMJ, et al. The use of genetic testing in hereditary colorectal cancer syndromes: genetic testing in HNPCC, (A)FAP and MAP. Clin Genet. 2007;72(6):562-567.
15. Aktan-Collan K, Mecklin JP, Järvinen H, et al. Predictive genetic testing for hereditary non-polyposis colorectal cancer: uptake and long-term satisfaction. Int J Cancer. 2000;89(1):44-50.
16. Lerman C. Genetic Testing in Families With Hereditary Nonpolyposis Colon Cancer. JAMA. 1999;281(17):1618.
17. Lynch HT, Lemon SJ, Karr B, et al. Etiology, natural history, management and molecular genetics of hereditary nonpolyposis colorectal cancer (Lynch syndromes): genetic counseling implications. Cancer Epidemiol Biomarkers Prev. 1997;6(12):987-991.
18. Sharaf RN, Myer P, Stave CD, Diamond LC, Ladabaum U. Uptake of genetic testing by relatives of lynch syndrome probands: a systematic review. Clin Gastroenterol Hepatol. 2013;11(9):1093-1100.
19. Kastrinos F, Stoffel EM. History, genetics, and strategies for cancer prevention in Lynch syndrome. Clin Gastroenterol Hepatol. 2014;12(5):715-727; quiz e41-43.
20. Roberts MC, Dotson WD, DeVore CS, et al. Delivery Of Cascade Screening For Hereditary Conditions: A Scoping Review Of The Literature. Health Affairs. 2018;37(5):801-808.
21. Menko FH, ter Stege JA, van der Kolk LE, et al. The uptake of presymptomatic genetic testing in hereditary breast-ovarian cancer and Lynch syndrome: a systematic review of the literature and implications for clinical practice. Familial Cancer. Published online May 30, 2018. doi:10.1007/s10689-018-0089-z
22. Accessed May 27, 2017. https://cancercontrol.cancer.gov/lynch-syndrome-workshop/
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24. Henrikson NB, Wagner JK, Hampel H, et al. What guidance does HIPAA offer to providers considering familial risk notification and cascade genetic testing? J Law Biosci. 2020;7(1):lsaa071.
25. Healther hampel review article later in new cites.
26. Rothstein MA. Reconsidering the duty to warn genetically at-risk relatives. Genetics in Medicine. 2018;20(3):285-290.
27. Shah SK, Hull SC, Spinner MA, et al. What Does the Duty to Warn Require? The American Journal of Bioethics. 2013;13(10):62-63.
28. Singh H, Schiesser R, Anand G, Richardson PA, El-Serag HB. Underdiagnosis of Lynch syndrome involves more than family history criteria. Clin Gastroenterol Hepatol. 2010;8(6):523-529.
29. Grover S, Stoffel EM, Bussone L, Tschoegl E, Syngal S. Physician assessment of family cancer history and referral for genetic evaluation in colorectal cancer patients. Clin Gastroenterol Hepatol. 2004;2(9):813-819.
30. Chou AF, Duncan AR, Hallford G, Kelley DM, Dean LW. Barriers and strategies to integrate medical genetics and primary care in underserved populations: a scoping review. J Community Genet. 2021;12(3):291-309.
31. McCann S, MacAuley D, Barnett Y, et al. Family communication, genetic testing and colonoscopy screening in hereditary non-polyposis colon cancer: a qualitative study. Psychooncology. 2009;18(11):1208-1215.
32. Stoffel EM, Ford B, Mercado RC, et al. Sharing Genetic Test Results in Lynch Syndrome: Communication With Close and Distant Relatives. Clinical Gastroenterology and Hepatology. 2008;6(3):333-338.
33. Gaff CL, Clarke AJ, Atkinson P, et al. Process and outcome in communication of genetic information within families: a systematic review. Eur J Hum Genet. 2007;15(10):999-1011.
34. Mesters I, Ausems M, Eichhorn S, Vasen H. Informing one’s family about genetic testing for hereditary non-polyposis colorectal cancer (HNPCC): a retrospective exploratory study. Familial Cancer. 2005;4(2):163-167.
35. Ersig AL, Williams JK, Hadley DW, Koehly LM. Communication, encouragement, and cancer screening in families with and without mutations for hereditary nonpolyposis colorectal cancer: A pilot study. Genetics in Medicine. 2009;11(10):728-734.
36. Murakami Y, Okamura H, Sugano K, et al. Psychologic distress after disclosure of genetic test results regarding hereditary nonpolyposis colorectal carcinoma: A preliminary report. Cancer. 2004;101(2):395-403.
37. Peterson SK. The role of the family in genetic testing: theoretical perspectives, current knowledge, and future directions. Health Educ Behav. 2005;32(5):627-639.
38. Bowen D, Jabson J, Haddock N, Hay J, Edwards K. Skin care behaviors among melanoma survivors. Psychooncology. 2012;21(12):1285-1291.
39. Pitceathly C, Maguire P. The psychological impact of cancer on patients’ partners and other key relatives. European Journal of Cancer. 2003;39(11):1517-1524.
40. Pho K, Geller A, Schroy PC. Lack of communication about familial colorectal cancer risk associated with colorectal adenomas (United States). Cancer Causes Control. 2000;11(6):543-546.
41. Olson S, National Research Council (U.S.), National Research Council (U.S.), National Academies Press (U.S.), eds. Toward an Integrated Science of Research on Families: Workshop Report. National Academies Press; 2011.
42. Novilla MLB, Barnes MD, De La Cruz NG, Williams PN, Rogers J. Public health perspectives on the family: an ecological approach to promoting health in the family and community. Fam Community Health. 2006;29(1):28-42.
43. Bowen DJ, Albrecht T, Hay J, et al. Communication Among Melanoma Family Members. J Health Commun. 2017;22(3):198-204.
44. Prince AER, Cadigan RJ, Henderson GE, et al. Is there evidence that we should screen the general population for Lynch syndrome with genetic testing? A systematic review. Pharmgenomics Pers Med. 2017;10:49-60.
45. Heald B, Marquard J, Funchain P. Strategies for clinical implementation of screening for hereditary cancer syndromes. Semin Oncol. 2016;43(5):609-614.
46. Kennelly RP, Gryfe R, Winter DC. Familial colorectal cancer: Patient assessment, surveillance and surgical management. Eur J Surg Oncol. 2017;43(2):294-302.
47. Ned RM, Sijbrands EJG. Cascade Screening for Familial Hypercholesterolemia (FH). PLoS Currents. 2011;3:RRN1238.
48. Braithwaite DO, Baxter LA. Engaging Theories in Family Communication: Multiple Perspectives. SAGE Publications; 2006.
49. Leventhal H, Brissette I, Leventhal EA. The common-sense model of self-regulation of health and illness. In: The Self-Regulation of Health and Illness Behaviour. Routledge; 2003:42-65.
50. Leventhal H, Phillips LA, Burns E. The Common-Sense Model of Self-Regulation (CSM): a dynamic framework for understanding illness self-management. J Behav Med. 2016;39(6):935-946.
51. Cameron LD, Marteau TM, Brown PM, Klein WMP, Sherman KA. Communication strategies for enhancing understanding of the behavioral implications of genetic and biomarker tests for disease risk: the role of coherence. J Behav Med. 2012;35(3):286-298.
52. Mvundura M, Grosse SD, Hampel H, Palomaki GE. The cost-effectiveness of genetic testing strategies for Lynch syndrome among newly diagnosed patients with colorectal cancer. Genet Med. 2010;12(2):93-104.
53. Grosse S. When is Genomic Testing Cost-Effective? Testing for Lynch Syndrome in Patients with Newly-Diagnosed Colorectal Cancer and Their Relatives. Healthcare. 2015;3(4):860-878.
54. Grosse SD, Palomaki GE, Mvundura M, Hampel H. The cost-effectiveness of routine testing for Lynch syndrome in newly diagnosed patients with colorectal cancer in the United States: corrected estimates. Genetics in Medicine. 2015;17(6):510-511.
55. Bowen DJ, Hyams T, Laurino M, et al. Development of FamilyTalk: An intervention to support communication and educate families about colorectal cancer risk. J Cancer Educ. 2020;35(3):470-478.
56. Makhnoon S, Bowen DJ, Shirts BH, et al. Relationship between genetic knowledge and familial communication of CRC risk and intent to communicate CRCP genetic information: insights from FamilyTalk eMERGE III. Transl Behav Med. 2021;11(2):563-572.
2. Aarnio M, Sankila R, Pukkala E, et al. Cancer risk in mutation carriers of DNA-mismatch-repair genes. Int J Cancer. 1999;81(2):214-218.
3. Møller P, Seppälä T, Bernstein I, et al. Cancer incidence and survival in Lynch syndrome patients receiving colonoscopic and gynaecological surveillance: first report from the prospective Lynch syndrome database. Gut. Published online December 9, 2015. doi:10.1136/gutjnl-2015-309675
4. Hampel H. Genetic counseling and cascade genetic testing in Lynch syndrome. Fam Cancer. 2016;15(3):423-427.
5. Wolf SM, Branum R, Koenig BA, et al. Returning a Research Participant’s Genomic Results to Relatives: Analysis and Recommendations. J Law Med Ethics. 2015;43(3):440-463.
6. Krawczak M, Cooper DN, Schmidtke J. Estimating the efficacy and efficiency of cascade genetic screening. Am J Hum Genet. 2001;69(2):361-370.
7. Ladabaum U, Wang G, Terdiman J, et al. Strategies to identify the Lynch syndrome among patients with colorectal cancer: a cost-effectiveness analysis. Ann Intern Med. 2011;155(2):69-79.
8. Snowsill T, Huxley N, Hoyle M, et al. A systematic review and economic evaluation of diagnostic strategies for Lynch syndrome. Health Technology Assessment. 2014;18(58):1-406.
9. Winawer SJ, Krabshuis J, Lambert R, OʼBrien M, Fried M. Cascade Colorectal Cancer Screening Guidelines: A Global Conceptual Model. Journal of Clinical Gastroenterology. 2011;45(4):297-300.
10. Accessed May 25, 2017. https://www.cdc.gov/genomics/gtesting/egapp/recommend/lynch.htm
11. Ponz de Leon M, Benatti P, Di Gregorio C, et al. Genetic testing among high-risk individuals in families with hereditary nonpolyposis colorectal cancer. British Journal of Cancer. 2004;90(4):882-887.
12. Aktan-Collan K, Haukkala A, Pylvänäinen K, et al. Direct contact in inviting high-risk members of hereditary colon cancer families to genetic counselling and DNA testing. J Med Genet. 2007;44(11):732-738.
13. Hadley DW, Jenkins J, Dimond E, et al. Genetic counseling and testing in families with hereditary nonpolyposis colorectal cancer. Arch Intern Med. 2003;163(5):573-582.
14. Ramsoekh D, van Leerdam ME, Tops CMJ, et al. The use of genetic testing in hereditary colorectal cancer syndromes: genetic testing in HNPCC, (A)FAP and MAP. Clin Genet. 2007;72(6):562-567.
15. Aktan-Collan K, Mecklin JP, Järvinen H, et al. Predictive genetic testing for hereditary non-polyposis colorectal cancer: uptake and long-term satisfaction. Int J Cancer. 2000;89(1):44-50.
16. Lerman C. Genetic Testing in Families With Hereditary Nonpolyposis Colon Cancer. JAMA. 1999;281(17):1618.
17. Lynch HT, Lemon SJ, Karr B, et al. Etiology, natural history, management and molecular genetics of hereditary nonpolyposis colorectal cancer (Lynch syndromes): genetic counseling implications. Cancer Epidemiol Biomarkers Prev. 1997;6(12):987-991.
18. Sharaf RN, Myer P, Stave CD, Diamond LC, Ladabaum U. Uptake of genetic testing by relatives of lynch syndrome probands: a systematic review. Clin Gastroenterol Hepatol. 2013;11(9):1093-1100.
19. Kastrinos F, Stoffel EM. History, genetics, and strategies for cancer prevention in Lynch syndrome. Clin Gastroenterol Hepatol. 2014;12(5):715-727; quiz e41-43.
20. Roberts MC, Dotson WD, DeVore CS, et al. Delivery Of Cascade Screening For Hereditary Conditions: A Scoping Review Of The Literature. Health Affairs. 2018;37(5):801-808.
21. Menko FH, ter Stege JA, van der Kolk LE, et al. The uptake of presymptomatic genetic testing in hereditary breast-ovarian cancer and Lynch syndrome: a systematic review of the literature and implications for clinical practice. Familial Cancer. Published online May 30, 2018. doi:10.1007/s10689-018-0089-z
22. Accessed May 27, 2017. https://cancercontrol.cancer.gov/lynch-syndrome-workshop/
23. Weaver M. The Double Helix: Applying an Ethic of Care to the Duty to Warn Genetic Relatives of Genetic Information. Bioethics. 2016;30(3):181-187.
24. Henrikson NB, Wagner JK, Hampel H, et al. What guidance does HIPAA offer to providers considering familial risk notification and cascade genetic testing? J Law Biosci. 2020;7(1):lsaa071.
25. Healther hampel review article later in new cites.
26. Rothstein MA. Reconsidering the duty to warn genetically at-risk relatives. Genetics in Medicine. 2018;20(3):285-290.
27. Shah SK, Hull SC, Spinner MA, et al. What Does the Duty to Warn Require? The American Journal of Bioethics. 2013;13(10):62-63.
28. Singh H, Schiesser R, Anand G, Richardson PA, El-Serag HB. Underdiagnosis of Lynch syndrome involves more than family history criteria. Clin Gastroenterol Hepatol. 2010;8(6):523-529.
29. Grover S, Stoffel EM, Bussone L, Tschoegl E, Syngal S. Physician assessment of family cancer history and referral for genetic evaluation in colorectal cancer patients. Clin Gastroenterol Hepatol. 2004;2(9):813-819.
30. Chou AF, Duncan AR, Hallford G, Kelley DM, Dean LW. Barriers and strategies to integrate medical genetics and primary care in underserved populations: a scoping review. J Community Genet. 2021;12(3):291-309.
31. McCann S, MacAuley D, Barnett Y, et al. Family communication, genetic testing and colonoscopy screening in hereditary non-polyposis colon cancer: a qualitative study. Psychooncology. 2009;18(11):1208-1215.
32. Stoffel EM, Ford B, Mercado RC, et al. Sharing Genetic Test Results in Lynch Syndrome: Communication With Close and Distant Relatives. Clinical Gastroenterology and Hepatology. 2008;6(3):333-338.
33. Gaff CL, Clarke AJ, Atkinson P, et al. Process and outcome in communication of genetic information within families: a systematic review. Eur J Hum Genet. 2007;15(10):999-1011.
34. Mesters I, Ausems M, Eichhorn S, Vasen H. Informing one’s family about genetic testing for hereditary non-polyposis colorectal cancer (HNPCC): a retrospective exploratory study. Familial Cancer. 2005;4(2):163-167.
35. Ersig AL, Williams JK, Hadley DW, Koehly LM. Communication, encouragement, and cancer screening in families with and without mutations for hereditary nonpolyposis colorectal cancer: A pilot study. Genetics in Medicine. 2009;11(10):728-734.
36. Murakami Y, Okamura H, Sugano K, et al. Psychologic distress after disclosure of genetic test results regarding hereditary nonpolyposis colorectal carcinoma: A preliminary report. Cancer. 2004;101(2):395-403.
37. Peterson SK. The role of the family in genetic testing: theoretical perspectives, current knowledge, and future directions. Health Educ Behav. 2005;32(5):627-639.
38. Bowen D, Jabson J, Haddock N, Hay J, Edwards K. Skin care behaviors among melanoma survivors. Psychooncology. 2012;21(12):1285-1291.
39. Pitceathly C, Maguire P. The psychological impact of cancer on patients’ partners and other key relatives. European Journal of Cancer. 2003;39(11):1517-1524.
40. Pho K, Geller A, Schroy PC. Lack of communication about familial colorectal cancer risk associated with colorectal adenomas (United States). Cancer Causes Control. 2000;11(6):543-546.
41. Olson S, National Research Council (U.S.), National Research Council (U.S.), National Academies Press (U.S.), eds. Toward an Integrated Science of Research on Families: Workshop Report. National Academies Press; 2011.
42. Novilla MLB, Barnes MD, De La Cruz NG, Williams PN, Rogers J. Public health perspectives on the family: an ecological approach to promoting health in the family and community. Fam Community Health. 2006;29(1):28-42.
43. Bowen DJ, Albrecht T, Hay J, et al. Communication Among Melanoma Family Members. J Health Commun. 2017;22(3):198-204.
44. Prince AER, Cadigan RJ, Henderson GE, et al. Is there evidence that we should screen the general population for Lynch syndrome with genetic testing? A systematic review. Pharmgenomics Pers Med. 2017;10:49-60.
45. Heald B, Marquard J, Funchain P. Strategies for clinical implementation of screening for hereditary cancer syndromes. Semin Oncol. 2016;43(5):609-614.
46. Kennelly RP, Gryfe R, Winter DC. Familial colorectal cancer: Patient assessment, surveillance and surgical management. Eur J Surg Oncol. 2017;43(2):294-302.
47. Ned RM, Sijbrands EJG. Cascade Screening for Familial Hypercholesterolemia (FH). PLoS Currents. 2011;3:RRN1238.
48. Braithwaite DO, Baxter LA. Engaging Theories in Family Communication: Multiple Perspectives. SAGE Publications; 2006.
49. Leventhal H, Brissette I, Leventhal EA. The common-sense model of self-regulation of health and illness. In: The Self-Regulation of Health and Illness Behaviour. Routledge; 2003:42-65.
50. Leventhal H, Phillips LA, Burns E. The Common-Sense Model of Self-Regulation (CSM): a dynamic framework for understanding illness self-management. J Behav Med. 2016;39(6):935-946.
51. Cameron LD, Marteau TM, Brown PM, Klein WMP, Sherman KA. Communication strategies for enhancing understanding of the behavioral implications of genetic and biomarker tests for disease risk: the role of coherence. J Behav Med. 2012;35(3):286-298.
52. Mvundura M, Grosse SD, Hampel H, Palomaki GE. The cost-effectiveness of genetic testing strategies for Lynch syndrome among newly diagnosed patients with colorectal cancer. Genet Med. 2010;12(2):93-104.
53. Grosse S. When is Genomic Testing Cost-Effective? Testing for Lynch Syndrome in Patients with Newly-Diagnosed Colorectal Cancer and Their Relatives. Healthcare. 2015;3(4):860-878.
54. Grosse SD, Palomaki GE, Mvundura M, Hampel H. The cost-effectiveness of routine testing for Lynch syndrome in newly diagnosed patients with colorectal cancer in the United States: corrected estimates. Genetics in Medicine. 2015;17(6):510-511.
55. Bowen DJ, Hyams T, Laurino M, et al. Development of FamilyTalk: An intervention to support communication and educate families about colorectal cancer risk. J Cancer Educ. 2020;35(3):470-478.
56. Makhnoon S, Bowen DJ, Shirts BH, et al. Relationship between genetic knowledge and familial communication of CRC risk and intent to communicate CRCP genetic information: insights from FamilyTalk eMERGE III. Transl Behav Med. 2021;11(2):563-572.