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A clinical perspective on ethical arguments around prenatal diagnosis and preimplantation genetic diagnosis for later onset inherited cancer predispositions

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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.

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Notes

  1. 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.

  2. The penetrance of a condition is the probability that a person who carries a gene mutation will develop the condition.

  3. 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.

  4. 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.

  5. 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.

  6. 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

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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.

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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

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