Douglas Easton - Overview
Our focus is on genetic susceptibility to common
cancers, with particular emphasis on breast, ovarian and prostate cancer,
and melanoma. Our general aims are: to identify genes predisposing to
cancer, through linkage or association studies; to define the frequency
and penetrance associated with different disease causing mutations; and
to examine interactions between genetic risks and environmental risk factors.
Parallel to these studies, we have an active programme in developing statistical
methodology and software for genetic studies.
1. Genetic Epidemiology of Breast and Ovarian Cancer
A major interest of the Unit is the epidemiology of the BRCA1 and BRCA2
genes that predispose strongly to breast and ovarian cancer. In a series
of collaborative studies we have provided estimates of age-specific risk
cancer risks in carriers of mutations in these genes that are the basis
for genetic counselling, and estimated the contribution of these genes
to breast and ovarian cancer incidence in the population. We have demonstrated
that risks in BRCA1/2 mutation carriers vary by mutation position; that
mutations predispose more moderately to other cancer types (for example,
prostate and pancreas); and that the pathology and clinical behaviour
of breast cancers in BRCA1 (but not BRCA2) carriers is distinct (for example,
they are usually high grade and receptor negative, and have poorer prognosis).
A major ongoing project (the EMBRACE study) seeks to identify lifestyle
and genetic modifiers of risk in BRCA1/2 carriers, and to evaluate prospectively
possible interventions to reduce risk in carriers.
2. Identification of further cancer predisposition genes
Our ongoing strategies are:
(a) identification of further high risk susceptibility genes through genetic
linkage studies in multiple case families, specifically by coordinating
large collaborative studies in breast, prostate and testis cancer.
(b) identification of commoner, lower penetrance genes through large scale
case-control association studies (primarily in breast and ovarian cancer).
Currently this is ongoing on a candidate gene basis (for example, examining
polymorphisms in genes involved in DNA repair) but we are establishing
sample collections from large population-based series of cancer patients
to allow empirical genomic searches once this becomes possible.
(c) using quantitative phenotypes associated with cancer risk, specifically
using naevus density to map further melanoma genes.
