Clinical cancer genetics

This page contains information on genetic testing and cancer, surveillance (screening for early signs of cancer), and familial cancer prevention.

The discovery of inherited, high-risk cancer genes and an increased understanding of their role in the disease, has paved the way for predictive genetic tests. These can determine whether an individual with a strong family history of cancer is at an increased risk of developing the disease.

Patients with a family history of cancer are referred to a genetics clinic by their GP or secondary care provider. Referrals are made according to guidelines published by local Cancer Networks or by the National Institute for Health and Clinical Excellence. 1

In the UK there are more than 30 NHS clinical genetics centres, many of which carry out cancer genetic testing, and have an associated family cancer clinic. 2 Cancer genetics referrals have increased significantly in recent years, and now account for over a third of the workload of most clinical genetics departments. The bulk of these referrals relate to a family history of breast, ovarian or bowel cancers.

Genetic testing and cancer

Predictive genetic testing can be carried out for any of the known, high-risk cancer susceptibility genes, including, for example, BRCA1 and BRCA2 (breast and ovarian cancer), APC (bowel cancer), E-cadherin (stomach cancer), RET (multiple endocrine neoplasia) and RB1 (retinoblastoma). 3 At present, data on lower-risk polymorphisms are too preliminary to be applied in a clinical setting.

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Prior to any genetic testing, genetics clinics make an initial assessment of the person's cancer risk based on a detailed family history. This often requires histological confirmation of cancer diagnoses in family members. The main indicators of a high-risk faulty gene in a family are summarised in Table 4.1.

Those considered to be at increased risk are then given an opportunity to discuss their level of risk and, based on this, to explore their options regarding screening and prevention and/or genetic testing. 4

Table 4.1: Some indications of genetic predisposition to cancer

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The follow-up for individuals testing positive for a cancer-susceptibility mutation varies depending on the disease gene in question (see Table 4.2 for some of the management options available for the common familial cancers). There are some inherited cancer syndromes, for example Li-Fraumeni syndrome, for which effective screening, prevention or treatment is not currently possible. This should be carefully discussed before a predictive genetic test is performed.

The benefits of testing for mutations in the BRCA, APC and mismatch repair genes are clearer, since surveillance and prevention strategies are available (see our section on( surveillance).

Table 4.2: Common cancers with an inherited component and management options for people carrying the mutation

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The psychological consequences of learning one's risk of cancer can be considerable, regardless of the cancer type and the options for follow-up. Geneticists and genetic counsellors play a vital role in discussing the practical and psychological implications of testing, and in reducing anxiety.

Surveillance (screening for early signs of cancer)

People at high risk of certain cancers, including bowel or breast cancer, may be offered regular surveillance to check for early signs of the disease. For familial bowel cancer, endoscopic examination of the colon is carried out to detect early cancer or precancerous polyps. Women with BRCA gene mutations are offered regular mammograms and/or MRI scans, depending on their age. 5

For other cancers, there is still insufficient evidence for the effectiveness of screening, but much research is underway in this field. Approximately 10 per cent of ovarian cancers have a hereditary component. Currently, women at high risk of the disease, who are not planning to have prophylactic surgery, can request annual screening, using measurement of the CA125 tumour marker and/or transvaginal ultrasound.

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However, there is currently no data on how effective this screening actually is in increasing survival rates. The UK Familial Ovarian Cancer Screening Study is looking at screening for high-risk women, with the aim of developing a model for predicting risk of developing ovarian cancer. 6

The IMPACT study is assessing the benefits of prostate cancer screening in men carrying BRCA mutations. 7 The study will examine whether the PSA test or prostate biopsy are suitable tests for picking up early stage prostate cancer in these men.

Familial cancer prevention

Whenever possible, geneticists and genetic counsellors will also offer specific advice on cancer prevention measures to those at high risk. This may include lifestyle advice and, in some cases, consultation with a surgeon to discuss the options for prophylactic surgery.

Several studies have shown that prophylactic surgery can help reduce risk of developing some hereditary cancers. Examples include mastectomy and oophorectomy in BRCA mutation carriers, 8 colectomy in people with FAP, 9 and removal of polyps in HNPCC families. 10

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Chemoprevention trials investigate drugs that may be able to reduce the risk of a cancer developing. Drugs that have been studied in this context include anti-oestrogens (breast cancer), 11, 12 oral contraceptives (ovarian cancer) 13 and aspirin (bowel cancer caused by FAP). 14 Successful trials include the use of tamoxifen to reduce the incidence of breast cancer in women at high-risk of the disease. 15

 
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References for clinical cancer genetics

  1. National Institute for Health and Clinical Excellence (NICE).
  2. UKGTN Laboratories.
  3. UKGTN NHS Directory of Molecular Genetic Testing.
  4. Emery, J., A. Lucassen, and M. Murphy, Common hereditary cancers and implications for primary care. Lancet, 2001. 358(9275): p. 56-63
  5. NICE Guidance - CG41 Familial breast cancer
  6. Breakthrough Breast Cancer.
  7. Impact Study 2007.
  8. Calderon-Margalit, R. and O. Paltiel, Prevention of breast cancer in women who carry BRCA1 or BRCA2 mutations: a critical review of the literature. Int J Cancer, 2004. 112(3): p. 357-64
  9. Jarvinen, H.J., Epidemiology of familial adenomatous polyposis in Finland: impact of family screening on the colorectal cancer rate and survival. Gut, 1992. 33(3): p. 357-60
  10. Jarvinen, H.J., et al., Controlled 15-year trial on screening for colorectal cancer in families with hereditary nonpolyposis colorectal cancer. Gastroenterology, 2000. 118(5): p. 829-34
  11. Jones, P.A. and S.B. Baylin, The fundamental role of epigenetic events in cancer. Nat Rev Genet, 2002. 3(6): p. 415-28
  12. IBIS Trials.
  13. Narod, S.A., et al., Oral contraceptives and the risk of hereditary ovarian cancer. Hereditary Ovarian Cancer Clinical Study Group. N Engl J Med, 1998. 339(7): p. 424-8
  14. Asano, T.K. and R.S. McLeod, Non steroidal anti-inflammatory drugs (NSAID) and Aspirin for preventing colorectal adenomas and carcinomas. Cochrane Database Syst Rev, 2004(2): p. CD004079
  15. Cuzick, J., et al., Long-term results of tamoxifen prophylaxis for breast cancer--96-month follow-up of the randomized IBIS-I trial. J Natl Cancer Inst, 2007. 99(4): p. 272-82