Conclusion

The rapidly evolving practice of clinical genetics is throwing up many questions to which we do not yet have clear answers. This is nowhere more apparent than in the genetics of common cancers, including breast cancer, which is the fastest growing area of genetic medicine. If this chapter has dwelt on problems rather than solutions, this is a reflection of the current 'state of the art' rather than of any underlying pessimism. We live in exciting and, above all, hopeful times. Given the pace of...

What do we need from a screening test

A suitable screening test requires both high sensitivity and specificity. Women who have a positive screen require further investigation, often in the form of exploratory surgery. It is therefore imperative to maximize specificity in order to obtain a high positive predictive value, and to decrease the number of false-positive screens. In the general population, a specificity of 99.6 is required to achieve a positive predictive value of 10 (Jacobs and Oram, 1988). However, because of the much...

Predictive testing for BRCA1 and BRCA2

It is generally agreed that none of the currently available cancer susceptibility mutation tests is appropriate for the screening of asymptomatic persons in the general population, although the population-specific mutations described among Ashkenazi Jews and Icelanders, for example, may achieve that status in the future. The testing of unaffected members of a family known to carry a BRCA1 or BRCA2 mutation or another cancer-predisposing gene (known as a predictive genetic test) is probably best...

Introduction

Breast cancer is the most common cancer in women, accounting for 20 of all new cases of cancer. The lifetime risk to a woman in the UK is 1 in 12 females, with an incidence of less than 10 per 100 000 women aged under 30 years, rising to 300 per 100 000 in women aged over 85 years. Breast cancer can occur in sporadic and hereditary forms, and both forms are associated with modification to the genetic material. In the case of hereditary forms, a constitutive mutation in a specific gene...

Heterogeneity

As can be seen in Table 2.3, Ford et al. carried out heterogeneity analyses using BRCA1 2 linkage data. With the Cancer and Steroid Hormone (CASH) model being assumed for all genes, they estimated the proportions of families linked to each gene depending on the family structure and prevalence of cancer. This suggested that 52 of breast cancer in families was due to BRCA1 and 35 to BRCA2. They also estimated the proportions under the assumption that BRCA1 confers the risks estimated in previous...

Confidentiality of family medical history

A recurring theme in clinical genetics is the difficulty of balancing an individual's right to privacy against the duty to share relevant information with the wider family. The enormous increase in the potential for genetic analysis in recent years has raised public awareness of the risks of 'genetic discrimination' in education, employment, insurance and access to health care. These are genuine concerns that society must address but the initial reaction, which is often to propose legislation...

Pedigree analysis

For genetic counselling of women with a family history of breast cancer, the commonly employed model for estimating breast cancer risk is based on the Cancer and Steroid Hormone (CASH) study - a large population-based, case-control study of breast cancer comprising 4730 patients diagnosed at 20-54 years and 4688 control subjects. The Claus model is based on a genetic model of rare highly penetrant genes for susceptibility to breast cancer and therefore includes more information about family...

Low penetrancemodifier genes

Candidate genes with a function known to be consistent with a potential role in carcinogenesis have been studied to determine whether they influence the risk of breast cancer in both the general population and, more recently, in individuals carrying BRCA1 and BRCA2 gene mutations. The polymorphisms in these genes are usually common in the general population and may be associated with a small increased risk. They may only be seen to have an effect in carriers of other known gene mutations or in...

Familial Breast Ovarian Cancer

Hodgson and Neva E. Haites more information - www.cambridge.org 9780521803731 This book surveys the profound and far-reaching ramifications that have arisen from the very significant advances in our understanding of the genetic basis of familial breast and ovarian cancer. Written by international experts from Europe and North America, it provides the busy clinician with a contemporary and wide-ranging guide to the latest developments in the diagnosis, genetics,...