0
October 15, 1997, Vol 278, No. 15 >
ARTICLE | October 15, 1997

Predisposition Genetic Testing for Late-Onset Disorders in Adults: Title and subTitle BreakA Position Paper of the National Society of Genetic Counselors FREE

Wendy C. McKinnon, MS; Bonnie J. Baty, MS; Robin L. Bennett, MS; Monica Magee, MS; Whitney A. Neufeld-Kaiser, MS; Kathryn F. Peters, MS; Jill C. Sawyer, MS; Katherine A. Schneider, MPH
[+] Author Affiliations

Financial disclosures for Mss Baty, Bennett, and Schneider are listed at the end of this article.

Reprints: Wendy McKinnon, MS, Vermont Regional Genetics Center, 1 Mill St, Box B-10, Burlington, VT 05401 (e-mail: mckinnon@salus.med.uvm.edu).


JAMA. 1997;278(15):1217-1220. doi:10.1001/jama.1997.03550150021011
Text Size: A A A
Published online
Article
References

RAPID ADVANCES, such as those related to the Human Genome Project, have dramatically increased the number of available molecular genetic tests, and this number will only increase with future genetics research. Until recently, most such tests have been for rare monogenic conditions. Many of these single-gene disorders show signs or symptoms during childhood, while some, such as Huntington disease and adultonset polycystic kidney disease, have later onset. Molecular genetic tests have now become available for more common, complex conditions with onset later in life. Identification of cancer susceptibility genes1-6 and of genes leading to several neurogenetic disorders, including Alzheimer disease7 and some forms of ataxia,8 represents the start of a cascade of genes to be identified that confer susceptibility to adult-onset diseases. Understanding of the genetic basis for other complex diseases, such as diabetes, heart disease, and psychiatric disorders, is advancing at a rapid pace.9-11 These

REFERENCES

1 +
Miki Y, Swensen J, Shattuck-Eidens D, et al.  A strong candidate for the breast and ovarian cancer susceptibility gene BRCA1 . Science . 1994;;266:66-71.
2 +
Wooster R, Bignell G, Lancaster J, et al.  Identification of the breast cancer susceptibility gene BRCA2 . Nature . 1995;;378:780-792.
3 +
Fishel R, Lescoe MK, Rao MRS, et al.  The human mutator gene homolog MSH2 and its association with hereditary nonpolyposis colon cancer . Cell . 1993;;75:1027-1038.
4 +
Kawakami Y, Eliyahu S, Delgado CH, et al.  Cloning of the gene for a shared human melanoma antigen recognized by autologous T cells infiltrating into tumor . Proc Natl Acad Sci U S A .1994;;91:3515-3519.
5 +
Malkin D, Li FP, Strong LC, et al.  Germ line p53 mutations in a familial syndrome of breast cancer, sarcomas, and other neoplasms . Science . 1990;;1233-1238.
6 +
Van Heyningen V.  One gene—four syndromes . Nature . 1994;;367:319-320.
7 +
Pericak-Vance MA, Haines JL.  Genetic susceptibility to Alzheimer disease . Trends Genet . 1995;;11:504-508.
8 +
Rosenberg RN.  The genetic basis of ataxia . Clin Neurosci . 1995;;3:1-4.
9 +
Wagner A, Tibben A, Bruining GJ, et al.  Preliminary experience with predictive testing for insulin-dependent diabetes mellitus . Lancet . 1995;;346:380-381.
10 +
Keating MT, Sanguinetti MC.  Molecular genetic insights into cardiovascular disease . Science . 1996;;272:681-685.
11 +
Smith LB, Sapers B, Reus VI, Freimer NB.  Attitudes towards bipolar disorder and predictive genetic testing among patients and providers . J Med Genet . 1996;;33:544-549.
12 +
Andrews LB, Fullerton JE, Holtzman NA, Motulsky AG, eds. Assessing Genetic Risks: Implications for Health and Social Policy . Washington, DC: National Academy Press; 1994;.
13 +
Craufurd D, Tyler A.  Predictive testing for Huntington's disease: protocol for the UK Huntington's Prediction Consortium . J Med Genet . 1992;;29:915-918.
14 +
Quaid KA.  Presymptomatic testing for Huntington disease: recommendations for counseling . J Genet Couns . 1992;;1:277-302.
15 +
Broholm J, Cassiman JJ, Craufurd D, et al.  Guidelines for the molecular genetics predictive test in Huntington's disease: International Huntington Association and the World Federation of Neurology . J Med Genet . 1994;;31:555-559.
16 +
Li FP, Garber JE, Friend SH, et al.  Recommendations on predictive testing for germ line p53 mutations among cancer-prone individuals . J Natl Cancer Inst . 1992;;84:1156-1160.
17 +
Biesecker BB, Boehnke M, Calzone K, et al.  Genetic counseling for families with inherited susceptibility to breast and ovarian cancer . JAMA . 1993;;269:1970-1974.
18 +
 Correction : JAMA . 1993;;270:832.
19 +
Bowcock AM, Biesecker BB, Collins F, et al.  Statement of the American Society of Human Genetics on genetic testing for breast and ovarian cancer predisposition . Am J Hum Genet . 1994;;55:i-iv.
20 +
National Advisory Council for Human Genome Research.  Statement on use of DNA testing for presymptomatic identification of cancer risk . JAMA . 1994;;271:785.
21 +
Biesecker BB, Garber JE.  Testing and counseling adults for heritable cancer risk . J Natl Cancer Inst Monogr . 1995;;17:115-118.
22 +
Collins FS, Kahn MJE, Calzone KA, et al. National Action Plan on Breast Cancer Position Paper On Hereditary Susceptibility Testing for Breast Cancer . Washington, DC: National Action Plan on Breast Cancer; March 1996;.
23 +
 Statement of the American Society of Clinical Oncology: genetic testing for cancer susceptibility; adopted on February 20, 1996 . J Clin Oncol . 1996;;14:1730-1736; discussion, 1737-1740.
24 +
Peterson GM.  Genetic counseling and predictive testing for colorectal cancer risk . Int J Cancer . 1996;;69:53-54.
25 +
Baty BJ, Venne VL, McDonald J, et al.  BRCA1 testing: genetic counseling protocol development and counseling issues . J Genet Couns . 1997;;6:223-244.
26 +
Geller G, Botkin JR, Green MJ, et al.  Genetic testing for susceptibility to adult-onset cancer: the process and content of informed consent . JAMA . 1997;;277:1467-1474.
27 +
Resource document for curriculum development in cancer genetics education.  American Society of Clinical Oncology . J Clin Oncol . 1997;;15:2157-2169.
28 +
American College of Medical Genetics and American Society of Human Genetics Working Group on ApoE and Alzheimer Disease.  Statement on use of apolipoprotein E testing for Alzheimer disease . JAMA . 1995;;274:1627-1629.
29 +
National Ataxia Foundation. Guidelines for Gene Testing for Dominant Hereditary Ataxia . Wayzata, Minn: National Ataxia Foundation; 1997;.
30 +
Giardiello FM, Brensinger JD, Petersen GM, et al.  The use and interpretation of commercial APC gene testing for familial adenomatous polyposis . N Engl J Med . 1997;;336:823-827.
31 +
Bennett RL, Bird TD, Teri L.  Offering predictive testing for Huntington disease in a medical genetics clinic: practical applications . J Genet Couns . 1993;; 2:123-137.
32 +
McKinnon WC, Guttmacher AE, Greenblatt MS, et al.  The Familial Cancer Program of the Vermont Cancer Center: development of a cancer genetics program in a rural area . J Genet Couns . 1997;;6:131-145.
33 +
Peters J.  Familial cancer risk, part I: impact on today's oncology practice . J Oncol Manage . (September/October) 1994;:20-30.
34 +
Bennett RL, Steinhaus KA, Uhrich SB, et al.  Recommendations for standardized human pedigree nomenclature . J Genet Couns . 1995;;4:267-280.
35 +
Love RR, Evans AM,Josten DM.  The accuracy of patient reports of a family history of cancer . J Chronic Dis . 1985;;38:289-293.
36 +
Giardiello FM, Hamilton SR, Krush AJ, et al.  Treatment of colonic and rectal adenomas with sulindac in familial adenomatous polyposis . N Engl J Med . 1993;;328:1313-1316.
37 +
Jarvinen HJ, Medklin JP, Sistonen P.  Screening reduces colorectal cancer rate in families with hereditary non-polyposis colorectal cancer . Gastroenterology . 1995;;108:1405-1411.
38 +
Vasen HF A, van der Luijt RB, Slors JFM, et al.  Molecular genetic tests as a guide to surgical management of familial adenomatous polyposis . Lancet . 1996;;348:433-435.
39 +
Burke W, Daly M, Garber J, et al.  Recommendations for follow-up care of individuals with an inherited predisposition to cancer, II: BRCAl and BRCA2 . JAMA . 1997;;277:997-1003.
40 +
Codori AM, Brandt J.  Psychological costs and benefits of predictive testing for Huntington's disease . Am J Med Genet . 1994;;54:174-184.
41 +
Lerman C, Croyle R.  Emotional and behavioral responses to genetic testing for susceptibility to cancer . Oncology . 1996;;10:191-195.
42 +
Quaid KA, Wesson MK.  Exploration of the effects of predictive testing for Huntington disease on intimate relationships . Am J Med Genet . 1995;;57:46-51.
43 +
Kessler S.  Predictive testing for Huntington disease: a psychologist's view . Am J Med Genet . 1994;;54:161-166.
44 +
Mehlman MJ, Kodish ED, Whitehouse P, et al.  The need for anonymous genetic counseling and testing . Am J Hum Genet . 1996;;58:393-397.
45 +
Pretzer M.  Genetic conditions: who besides the patient do you tell? Med Econ . (June 9) ,1997;:129-132.
46 +
de Wert G.  Predictive testing for Huntington disease and the right not to know: some ethical considerations . Birth Defects . 1992;;28:133-138. Original Article Series.
47 +
Evans DGR, Blair V, Greenhalgh R, Hopwood P, Howell A.  The impact of genetic counselling on risk perception in women with a family history of breast cancer . Br J Cancer . 1994;;70:934-938.
48 +
Sharpe NF.  Informed consent and Huntington disease: a model for communication . Am J Med Genet . 1994;;50:239-246.
49 +
Geller G, Bernhardt BA, Helzsouer K, Holtzman NA, Stefanek M, Wilcox PM.  Informed consent and BRCAl testing . Nat Genet . 1995;;11:364.
50 +
Clinical Laboratory Improvement Amendments (CLIA). Federal Register . (February 28) ,1992;;57(40):§493.2, p7139; §493.3, p7140.
51 +
Holtzman NA, Watson MS, Barr PA, et al. The Task Force on Genetic Testing: promoting safe and effective genetic testing in the United States: principles and recommendations. Available at: http://ww2.med.jhu.edu/tfgtelsi. Accessed June 5, 1997.
52 +
Copley TT, Wiggins S, Dufrasne S, et al.  Are we of one mind? clinicians' and patients' opinions regarding the development of a service protocol for predictive testing for Huntington disease . Am J Med Genet . 1995;;58:59-69.
53 +
Lerman C, Narod S, Schulman K, et al.  BRCA1 testing in families with hereditary breast-ovarian cancer: a prospective study of patient decision making and outcomes . JAMA . 1996;;275:1885-1892.
54 +
Croyle RT, Smith KR, Botkin JR, Baty B, Nash J.  Psychological responses to BRCA1 mutation testing: preliminary findings . Health Psychol . 1997;;16:63-72.
55 +
Wexler N.  The Tiresias complex: Huntington's disease as a paradigm of testing for late-onset disorders . FASEB J . 1992;;6:2820-2825.
56 +
Burgess MM.  Ethical issues in genetic testing for Alzheimer's disease: lessons from Huntington's disease . Alzheimer Dis Assoc Disord . 1994;;8:71-78.
57 +
Bird TD, Bennett RL.  Why do DNA testing? practical and ethical implications of new neurogenetic tests . Ann Neurol . 1996;;38:141-146.
58 +
Botkin JR, Croyle RT, Smith KR, et al.  A model protocol for evaluating the behavioral and psychosocial effects of BRCAl testing . J Natl Cancer Inst . 1996;;88:872-882.
59 +
Healy B.  BRCA genes: bookmaking, fortunetelling, and medical care . N Engl J Med . 1997;;336:823-827.

Figures

Tables

Interactive Graphics

Video

Country-Specific Mortality and Growth Failure in Infancy and Yound Children and Association With Material Stature

Use interactive graphics and maps to view and sort country-specific infant and early dhildhood mortality and growth failure data and their association with maternal

1 +
Miki Y, Swensen J, Shattuck-Eidens D, et al.  A strong candidate for the breast and ovarian cancer susceptibility gene BRCA1 . Science . 1994;;266:66-71.
2 +
Wooster R, Bignell G, Lancaster J, et al.  Identification of the breast cancer susceptibility gene BRCA2 . Nature . 1995;;378:780-792.
3 +
Fishel R, Lescoe MK, Rao MRS, et al.  The human mutator gene homolog MSH2 and its association with hereditary nonpolyposis colon cancer . Cell . 1993;;75:1027-1038.
4 +
Kawakami Y, Eliyahu S, Delgado CH, et al.  Cloning of the gene for a shared human melanoma antigen recognized by autologous T cells infiltrating into tumor . Proc Natl Acad Sci U S A .1994;;91:3515-3519.
5 +
Malkin D, Li FP, Strong LC, et al.  Germ line p53 mutations in a familial syndrome of breast cancer, sarcomas, and other neoplasms . Science . 1990;;1233-1238.
6 +
Van Heyningen V.  One gene—four syndromes . Nature . 1994;;367:319-320.
7 +
Pericak-Vance MA, Haines JL.  Genetic susceptibility to Alzheimer disease . Trends Genet . 1995;;11:504-508.
8 +
Rosenberg RN.  The genetic basis of ataxia . Clin Neurosci . 1995;;3:1-4.
9 +
Wagner A, Tibben A, Bruining GJ, et al.  Preliminary experience with predictive testing for insulin-dependent diabetes mellitus . Lancet . 1995;;346:380-381.
10 +
Keating MT, Sanguinetti MC.  Molecular genetic insights into cardiovascular disease . Science . 1996;;272:681-685.
11 +
Smith LB, Sapers B, Reus VI, Freimer NB.  Attitudes towards bipolar disorder and predictive genetic testing among patients and providers . J Med Genet . 1996;;33:544-549.
12 +
Andrews LB, Fullerton JE, Holtzman NA, Motulsky AG, eds. Assessing Genetic Risks: Implications for Health and Social Policy . Washington, DC: National Academy Press; 1994;.
13 +
Craufurd D, Tyler A.  Predictive testing for Huntington's disease: protocol for the UK Huntington's Prediction Consortium . J Med Genet . 1992;;29:915-918.
14 +
Quaid KA.  Presymptomatic testing for Huntington disease: recommendations for counseling . J Genet Couns . 1992;;1:277-302.
15 +
Broholm J, Cassiman JJ, Craufurd D, et al.  Guidelines for the molecular genetics predictive test in Huntington's disease: International Huntington Association and the World Federation of Neurology . J Med Genet . 1994;;31:555-559.
16 +
Li FP, Garber JE, Friend SH, et al.  Recommendations on predictive testing for germ line p53 mutations among cancer-prone individuals . J Natl Cancer Inst . 1992;;84:1156-1160.
17 +
Biesecker BB, Boehnke M, Calzone K, et al.  Genetic counseling for families with inherited susceptibility to breast and ovarian cancer . JAMA . 1993;;269:1970-1974.
18 +
 Correction : JAMA . 1993;;270:832.
19 +
Bowcock AM, Biesecker BB, Collins F, et al.  Statement of the American Society of Human Genetics on genetic testing for breast and ovarian cancer predisposition . Am J Hum Genet . 1994;;55:i-iv.
20 +
National Advisory Council for Human Genome Research.  Statement on use of DNA testing for presymptomatic identification of cancer risk . JAMA . 1994;;271:785.
21 +
Biesecker BB, Garber JE.  Testing and counseling adults for heritable cancer risk . J Natl Cancer Inst Monogr . 1995;;17:115-118.
22 +
Collins FS, Kahn MJE, Calzone KA, et al. National Action Plan on Breast Cancer Position Paper On Hereditary Susceptibility Testing for Breast Cancer . Washington, DC: National Action Plan on Breast Cancer; March 1996;.
23 +
 Statement of the American Society of Clinical Oncology: genetic testing for cancer susceptibility; adopted on February 20, 1996 . J Clin Oncol . 1996;;14:1730-1736; discussion, 1737-1740.
24 +
Peterson GM.  Genetic counseling and predictive testing for colorectal cancer risk . Int J Cancer . 1996;;69:53-54.
25 +
Baty BJ, Venne VL, McDonald J, et al.  BRCA1 testing: genetic counseling protocol development and counseling issues . J Genet Couns . 1997;;6:223-244.
26 +
Geller G, Botkin JR, Green MJ, et al.  Genetic testing for susceptibility to adult-onset cancer: the process and content of informed consent . JAMA . 1997;;277:1467-1474.
27 +
Resource document for curriculum development in cancer genetics education.  American Society of Clinical Oncology . J Clin Oncol . 1997;;15:2157-2169.
28 +
American College of Medical Genetics and American Society of Human Genetics Working Group on ApoE and Alzheimer Disease.  Statement on use of apolipoprotein E testing for Alzheimer disease . JAMA . 1995;;274:1627-1629.
29 +
National Ataxia Foundation. Guidelines for Gene Testing for Dominant Hereditary Ataxia . Wayzata, Minn: National Ataxia Foundation; 1997;.
30 +
Giardiello FM, Brensinger JD, Petersen GM, et al.  The use and interpretation of commercial APC gene testing for familial adenomatous polyposis . N Engl J Med . 1997;;336:823-827.
31 +
Bennett RL, Bird TD, Teri L.  Offering predictive testing for Huntington disease in a medical genetics clinic: practical applications . J Genet Couns . 1993;; 2:123-137.
32 +
McKinnon WC, Guttmacher AE, Greenblatt MS, et al.  The Familial Cancer Program of the Vermont Cancer Center: development of a cancer genetics program in a rural area . J Genet Couns . 1997;;6:131-145.
33 +
Peters J.  Familial cancer risk, part I: impact on today's oncology practice . J Oncol Manage . (September/October) 1994;:20-30.
34 +
Bennett RL, Steinhaus KA, Uhrich SB, et al.  Recommendations for standardized human pedigree nomenclature . J Genet Couns . 1995;;4:267-280.
35 +
Love RR, Evans AM,Josten DM.  The accuracy of patient reports of a family history of cancer . J Chronic Dis . 1985;;38:289-293.
36 +
Giardiello FM, Hamilton SR, Krush AJ, et al.  Treatment of colonic and rectal adenomas with sulindac in familial adenomatous polyposis . N Engl J Med . 1993;;328:1313-1316.
37 +
Jarvinen HJ, Medklin JP, Sistonen P.  Screening reduces colorectal cancer rate in families with hereditary non-polyposis colorectal cancer . Gastroenterology . 1995;;108:1405-1411.
38 +
Vasen HF A, van der Luijt RB, Slors JFM, et al.  Molecular genetic tests as a guide to surgical management of familial adenomatous polyposis . Lancet . 1996;;348:433-435.
39 +
Burke W, Daly M, Garber J, et al.  Recommendations for follow-up care of individuals with an inherited predisposition to cancer, II: BRCAl and BRCA2 . JAMA . 1997;;277:997-1003.
40 +
Codori AM, Brandt J.  Psychological costs and benefits of predictive testing for Huntington's disease . Am J Med Genet . 1994;;54:174-184.
41 +
Lerman C, Croyle R.  Emotional and behavioral responses to genetic testing for susceptibility to cancer . Oncology . 1996;;10:191-195.
42 +
Quaid KA, Wesson MK.  Exploration of the effects of predictive testing for Huntington disease on intimate relationships . Am J Med Genet . 1995;;57:46-51.
43 +
Kessler S.  Predictive testing for Huntington disease: a psychologist's view . Am J Med Genet . 1994;;54:161-166.
44 +
Mehlman MJ, Kodish ED, Whitehouse P, et al.  The need for anonymous genetic counseling and testing . Am J Hum Genet . 1996;;58:393-397.
45 +
Pretzer M.  Genetic conditions: who besides the patient do you tell? Med Econ . (June 9) ,1997;:129-132.
46 +
de Wert G.  Predictive testing for Huntington disease and the right not to know: some ethical considerations . Birth Defects . 1992;;28:133-138. Original Article Series.
47 +
Evans DGR, Blair V, Greenhalgh R, Hopwood P, Howell A.  The impact of genetic counselling on risk perception in women with a family history of breast cancer . Br J Cancer . 1994;;70:934-938.
48 +
Sharpe NF.  Informed consent and Huntington disease: a model for communication . Am J Med Genet . 1994;;50:239-246.
49 +
Geller G, Bernhardt BA, Helzsouer K, Holtzman NA, Stefanek M, Wilcox PM.  Informed consent and BRCAl testing . Nat Genet . 1995;;11:364.
50 +
Clinical Laboratory Improvement Amendments (CLIA). Federal Register . (February 28) ,1992;;57(40):§493.2, p7139; §493.3, p7140.
51 +
Holtzman NA, Watson MS, Barr PA, et al. The Task Force on Genetic Testing: promoting safe and effective genetic testing in the United States: principles and recommendations. Available at: http://ww2.med.jhu.edu/tfgtelsi. Accessed June 5, 1997.
52 +
Copley TT, Wiggins S, Dufrasne S, et al.  Are we of one mind? clinicians' and patients' opinions regarding the development of a service protocol for predictive testing for Huntington disease . Am J Med Genet . 1995;;58:59-69.
53 +
Lerman C, Narod S, Schulman K, et al.  BRCA1 testing in families with hereditary breast-ovarian cancer: a prospective study of patient decision making and outcomes . JAMA . 1996;;275:1885-1892.
54 +
Croyle RT, Smith KR, Botkin JR, Baty B, Nash J.  Psychological responses to BRCA1 mutation testing: preliminary findings . Health Psychol . 1997;;16:63-72.
55 +
Wexler N.  The Tiresias complex: Huntington's disease as a paradigm of testing for late-onset disorders . FASEB J . 1992;;6:2820-2825.
56 +
Burgess MM.  Ethical issues in genetic testing for Alzheimer's disease: lessons from Huntington's disease . Alzheimer Dis Assoc Disord . 1994;;8:71-78.
57 +
Bird TD, Bennett RL.  Why do DNA testing? practical and ethical implications of new neurogenetic tests . Ann Neurol . 1996;;38:141-146.
58 +
Botkin JR, Croyle RT, Smith KR, et al.  A model protocol for evaluating the behavioral and psychosocial effects of BRCAl testing . J Natl Cancer Inst . 1996;;88:872-882.
59 +
Healy B.  BRCA genes: bookmaking, fortunetelling, and medical care . N Engl J Med . 1997;;336:823-827.

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