Abstract
Prenatal diagnosis (PND) and preimplantation genetic diagnosis (PGD) for later onset and/or reduced penetrance inherited cancer predispositions, e.g. familial adenomatous polyposis, hereditary non-polyposis colorectal cancer/Lynch syndrome and hereditary breast and ovarian cancer, raise a number of ethical issues. Some of these are the same as for conditions which present early in childhood, are fully penetrant and for which no/limited treatment options are possible; others relate to whether reduced penetrance and/or the availability of treatment mean that these are not serious (enough) conditions to warrant tests prior to/during pregnancy or to justify termination of pregnancy. However, attempts to reach a consensus on what counts as a serious (enough) condition in the context of PND and PGD have been unsuccessful. Such a definition may anyway be unhelpful if it cannot also take into account, for example, the woman’s/couple’s awareness and experience of the condition and the impact of the condition on affected individuals and their families. Individuals affected by, or at high risk of, later onset and/or reduced penetrance inherited cancer predispositions are generally supportive of access to PND and PGD for their own conditions, even if they would not consider using it themselves. Professionals working in clinical cancer genetics need to be prepared to discuss PND and PGD with this group of patients.
Similar content being viewed by others
Notes
FAP is a dominantly inherited predisposition to adenomatous colorectal polyps and bowel cancer. Polyps usually develop from puberty, and surveillance by colonoscopy starts from the age of 10–12 in children at ≥50% risk. There is an inevitable progression from polyps to malignancy in untreated patients, and colectomy is commonly carried out between the ages of 16–30.
The penetrance of a condition is the probability that a person who carries a gene mutation will develop the condition.
HNPCC/Lynch syndrome is a dominantly inherited predisposition to bowel and endometrial cancer in particular. Men have up to an 80% lifetime risk of bowel cancer, and women have up to a 70% lifetime risk of bowel cancer and a 60% lifetime risk of endometrial cancer. The bowel cancer risk increases from the mid-twenties, and the endometrial cancer risk increases from the mid-thirties. Sub-total colectomy is recommended for a primary bowel tumour; as the efficacy of endometrial screening is unproven, hysterectomy and bilateral salpingo-oophorectomy may be the most effective form of risk reduction.
BRCA1/2 are dominantly inherited genes which predispose to breast and ovarian cancer. Women have up to an 80% lifetime risk of breast cancer (from the early-thirties) and up to a 60% lifetime risk of ovarian cancer (from around 40). Mammography and MRI screening can detect early breast cancers, but there is up to a 60% risk of a second primary breast cancer. The breast cancers in BRCA1 tend to be high grade and oestrogen receptor negative, and are associated with a poor prognosis. The efficacy of ovarian screening is unproven. Therefore, bilateral mastectomy and/or salpingo-oophorectomy are the most effective risk reducing measures.
In January 2004, the UK government announced a review of the Human Fertilisation and Embryology Act 1990. Part of the reason for this was that some issues the HFEA had considered over the previous few years had not been envisaged when the 1990 Act was drawn up. The review led to the Human Fertilisation and Embryology Act 2008.
The Regional Genetics Service based in Manchester serves a population of 4.5 million in the North West of England.
Abbreviations
- ESHRE:
-
European Society of Human Reproduction and Embryology
- FAP:
-
Familial adenomatous polyposis
- HNPCC:
-
Hereditary non-polyposis colorectal cancer
- HFEA:
-
Human Fertilisation and Embryology Authority
- PGD:
-
Preimplantation genetic diagnosis
- PND:
-
Prenatal diagnosis
References
Ekwo EE, Kim J-O, Gosselink CA (1987) Parental perceptions of the burden of genetic disease. Am J Med Genet 28:955–963
Frets PG, Duivenvoorden HJ, Verhage F et al (1990) Factors influencing the reproductive decision after genetic counseling. Am J Med Genet 35:496–502
Drugan A, Greb A, Johnson MP et al (1990) Determinants of parental decisions to abort for chromosome abnormalities. Prenat Diagn 10:483–490
Wertz DC, Janes SR, Rosenfield JM et al (1992) Attitudes toward the prenatal diagnosis of cystic fibrosis: factors in decision making among affected families. Am J Hum Genet 50:1077–1085
Evans MI, Sobiecke MA, Krivchenia EL et al (1996) Parental decisions to terminate/continue following abnormal cytogenetic prenatal diagnosis: “What” is still more important than “When”. Am J Med Genet 61:353–355
Beeson D, Doksom T (2001) Family values and resistance to genetic counseling. In: Hoffmaster B (ed) Bioethics in context. Temple, Philadelphia
Middleton A, Hewison J, Mueller RF (2001) Prenatal diagnosis for inherited deafness—what is the potential demand? J Genet Couns 10:121–131
Gooding HC, Boehm K, Thompson RE et al (2002) Issues surrounding prenatal testing for achondroplasia. Prenat Diagn 22:933–940
Callahan D (1986) How technology is reframing the abortion debate. Hastings Cent Rep 16:33–42
Harris J (1985) The value of life. Routledge, London
Tooley M (1972) Abortion and infanticide. Philos Public Aff 2:37–65
Jones DG (1998) Anatomy and ethics: an exploration of some ethical dimensions of contemporary anatomy. Clin Anat 11:100–105
Marquis D (1989) Why abortion is immoral. J Philos 4:183–202
Finnis J (1994) Abortion and health care ethics. In: Gillon R (ed) Principles of health care ethics. John Wiley, Chichester
Reichlin M (1997) The argument from potential: a reappraisal. Bioethics 11:1–23
Warnock Report (1984) Report of the committee of inquiry into human fertilisation and embryology, cmnd 9314. HMSO, London
Glover J (1989) Fertility and the family: the Glover report on reproductive technologies to the European commission. Fourth Estate, London
Human Fertilisation and Embryology Act (1990) Available at http://www.opsi.gov.uk/acts/acts1990/Ukpga_19900037_en_1.htm cited 01/02/09
The 1990 Act was amended by the Human Fertilisation and Embryology Act (2008) Available at http://www.opsi.gov.uk/acts/acts2008/ukpga_20080022_en_1 cited 01/02/09
McLaren A (1986) Embryo research. Nature 320:570
Lockwood M (1988) Warnock versus Powell (and Harradine): when does potentiality count? Bioethics 2:187–213
Thornhill AR, de Die-Smulders CE, Geraedts JP et al (2005) ESHRE PGD consortium best practice guidelines for clinical preimplantation genetic diagnosis (PGD) and preimplantation genetic screening (PGS). Hum Reprod 20:35–48
Gunning J (1999) Legal regulation concerning preimplantation diagnosis. In: Hildt E, Graumann S (eds) Genetics in human reproduction. Ashgate, Aldershot, pp 261–272
Watt H (2004) Preimplantation genetic diagnosis: choosing the “Good Enough” child. Health Care Anal 12:51–60
Katz MG, Fitzgerald L, Bankier A et al (2002) Issues and concerns of couples presenting for preimplantation genetic diagnosis (PGD). Prenat Diagn 22:1117–1122
Kastrinos F, Stoffel EM, Balmaña J et al (2007) Attitudes toward prenatal genetic testing in patients with familial adenomatous polyposis. Am J Gastroenterol 102:1284–1290
Glover J (1992) Future people, disability, and screening. In: Laslett P, Fishkin J (eds) Justice between age groups and generations. Yale University Press, New Haven
Shakespeare T (1998) Choices and rights: eugenics, genetics and disability equality. Disabil Soc 13:665–681
Kerr A, Cunningham-Burley S, Amos A (1998) Drawing the line: an analysis of lay people’s discussions about the new genetics. Public Underst Sci 7:113–133
Parens E, Asch A (1999) The disability rights critique of prenatal genetic testing. Hastings Cent Rep 29(5):S1–S22
Wertz DC, Knoppers BM (2002) Serious genetic disorders: can or should they be defined? Am J Med Genet 108:29–35
HFEA (2007) List of conditions licensed by the HFEA. Available at http://www.hfea.gov.uk/docs/PGD_list.pdf cited 01/02/09 (this is not a complete list of licensed conditions)
HFEA (2004) HFEA licenses PGD for inherited colon cancer. Available at http://www.hfea.gov.uk/en/1049.html cited 01/02/09
HFEA (2005) Choices and boundaries: should people be able to select embryos free from an inherited susceptibility to cancer? Available at http://www.hfea.gov.uk/docs/Choices_Boundaries.pdf cited 01/02/09
HFEA (2006) Authority decision on the use of PGD for lower penetrance, later onset inherited conditions. Available at http://www.hfea.gov.uk/docs/The_Authority_decision_-_Choices_and_boundaries.pdf cited 01/02/09
Post SG (1992) Huntington’s disease: prenatal screening for late onset disease. J Med Ethics 18:75–78
Decruyenaere M, Evers-Kiebooms G, Boogaerts A et al (2007) The complexity of reproductive decision-making in asymptomatic carriers of the Huntington mutation. Eur J Hum Genet 15:453–462
Roberts C, Franklin S (2004) Experiencing new forms of genetic choice: Findings from an ethnographic study of preimplantation genetic diagnosis. Hum Fertil 7:285–293
Krahn T (2000) Preimplantation genetic diagnosis: does age of onset matter (anymore)? Med Health Care Philos 12:187–202
Robertson JA (2003) Extending preimplantation genetic diagnosis: the ethical debate ethical issues in new uses of preimplantation genetic diagnosis. Hum Reprod 18:465–471
Melville A (2008) Patients’ attitudes to the use of preimplantation genetic diagnosis for familial adenomatous polyposis. MSc Dissertation, University of Manchester
Musgrave H (2008) Patients’ attitudes to the use of preimplantation genetic diagnosis for hereditary non-polyposis colorectal cancer. MSc Dissertation, University of Manchester
Evans G, Baildam A, Brain A et al (2009) Risk reducing mastectomy: outcomes in 10 European Centres. J Med Genet 46:254–258
Metcalfe KA, Birenbaum-Carmeli D, Lubinski J et al, The Hereditary Breast Cancer Clinical Study Group (2008) International variation in rates of uptake of preventive options in BRCA1 and BRCA2 mutation carriers. Int J Cancer 122:2017–2022
de Wert G (1998) Ethics of predictive DNA-testing for hereditary breast and ovarian cancer. Patient Educ Couns 35:43–52
Menon U, Harper J, Sharma A et al (2007) Views of BRCA gene mutation carriers on preimplantation genetic diagnosis as a reproductive option for hereditary breast and ovarian cancer. Hum Reprod 22:1573–1577
Staton AD, Kurian AW, Cobb K et al (2008) Cancer risk reduction and reproductive concerns in female BRCA1/2 mutation carriers. Fam Cancer 7:179–186
Quinn G, Vadaparampil S, Wilson C et al (2009) Attitudes of high-risk women toward preimplantation genetic diagnosis. Fertil Steril 91:2361–2368
Fortuny D, Balmaña J, Graña B et al (2009) Opinion about reproductive decision making among individuals undergoing BRCA1/2 genetic testing in a multicentre Spanish cohort. Hum Reprod 24:1000–1006
Williams C, Ehrich K, Farsides B et al (2007) Facilitating choice, framing choice: staff views on widening the scope of preimplantation genetic diagnosis in the UK. Socl Sci Med 65:1094–1105
Scott R, Williams C, Ehrich K et al (2007) The appropriate extent of pre-implantation genetic diagnosis: health professionals’ and scientists’ views on the requirement for a significant risk of a serious genetic condition. Med Law Rev 15:320–356
International Huntington Association and World Federation of Neurology Research Group on Huntington’s disease (1994) Guidelines for the molecular genetics predictive test in Huntington’s disease. J Med Genet 31:555–559
Bloch M, Hayden MR (1990) Opinion: predictive testing for Huntington disease in childhood: challenges and implications. Am J Hum Genet 46:1–4
Working Party of the Clinical Genetics Society (1994) Report on the genetic testing of children. J Med Genet 31:785–797
The American Society of Human Genetics Board of Directors, The American College of Medical Genetics Board of Directors (1995) Points to consider: ethical, legal, and psychosocial implications of genetic testing in children and adolescents. Am J Hum Genet 57:1233–1241
American College of Obstetricians, Gynecologists (2008) Committee opinion no. 410: ethical issues in genetic testing. Obstet Gynecol 111:1495–1502
Feinberg J (1980) The child’s right to an open future. In: Aiken W, La Fallette H (eds) Whose child? Children’s rights, parental authority and state power. Littlefield Adams, Totowa
Davis DS (1997) Genetic dilemmas and the child’s right to an open future. Hastings Cent Rep 27:7–15
Thornhill AR, de Die-Smulders CE, Geraedts JP et al (2005) ESHRE PGD consortium best practice guidelines for clinical preimplantation genetic diagnosis (PGD) and preimplantation genetic screening (PGS). Hum Reprod 20:35–48
HFEA (2008) Human fertilisation and embryology authority code of practice, 8th edn (consultation draft). pp 82–83 Available at http://www.hfea.gov.uk/docs/2008_11_12_CoP8_Code_for_consultation_final_for_website1.pdf cited 01/02/09
Goossens V, Harton G, Moutou C et al. (2008) ESHRE PGD Consortium data collection VIII: cycles from January to December 2005 with pregnancy follow-up to October 2006 Hum. Reprod 23:2629–2645 Supplementary Table IVc: List of indications under “others” for monogenic diseases with PCR, data VIII http://humrep.oxfordjournals.org/cgi/data/den238/DC1/1 cited 06/06/09
Goossens V, Harton G, Moutou C et al. (2009) ESHRE PGD Consortium data collection IX: cycles from January to December 2006 with pregnancy follow-up to October 2007 Hum. Reprod Advance Access April 29, 2009; doi: doi:10.1093/humrep/dep059 Supplementary Table IVc: List of indications under “others” for monogenic diseases, data IX http://humrep.oxfordjournals.org/cgi/data/dep059/DC1/3 cited 06/06/09
Clarke A (1991) Is non-directive genetic counselling possible? Lancet 335:1145–1147
Sorenson JR (1993) Genetic counseling: values that have mattered. In: Bartels DM, LeRoy BS, Caplan AL (eds) Prescribing our future. Aldine de Gruyter, New York
Resta RG (1997) Eugenics and nondirectiveness in genetic counseling. J Genet Couns 6:255–258
Kessler S (1997) Psychological aspects of genetic counseling. XI. Nondirectiveness revisited. Am J Med Genet 72:164–171
American Society of Human Genetics Ad Hoc Committee on Genetic Counseling (1975) Genetic counseling. Am J Hum Genet 27:240–242
Veatch RM (1972) Models for ethical medicine in a revolutionary age. What physician–patient roles foster the most ethical relationship? Hastings Cent Rep 2:5–7
Parker M (2001) Genetics and the interpersonal elaboration of ethics. Theor Med 22:451–459
Lehmann LS, Weeks JC, Klar N et al (2000) Disclosure of familial genetic information: perceptions of the duty to inform. Am J Med 109:705–711
Claes E, Evers-Kiebooms G, Boogaerts A et al (2003) Communication with close and distant relatives in the context of hereditary breast and ovarian cancer in cancer patients. Am J Med Genet 116A:11–19
Hallowell N, Foster C, Eeles R et al (2003) Balancing autonomy and responsibility: the ethics of generating and disclosing genetic information. J Med Ethics 29:74–83
Plantinga L, Natowicz MR, Kass NE et al (2003) Disclosure, confidentiality and families: experiences and attitudes of those with genetic versus nongenetic medical conditions. Am J Med Genet 119C:51–59
Acknowledgments
Thank you to Lauren Kerzin-Storrar, Anneke Lucassen and Rhona MacLeod and the reviewers for their helpful comments on the previous draft of this paper. Tara Clancy is supported by the Manchester Academic Health Sciences Centre and the NIHR Manchester Biomedical Research Centre.
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Clancy, T. A clinical perspective on ethical arguments around prenatal diagnosis and preimplantation genetic diagnosis for later onset inherited cancer predispositions. Familial Cancer 9, 9–14 (2010). https://doi.org/10.1007/s10689-009-9271-7
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s10689-009-9271-7