Section of Cancer Genetics

Section Highlights
The major scientific focus of the Section of Cancer Genetics is the study of inherited susceptibility to cancer. Most common types of human cancer include a proportion of cases that are attributable to inherited susceptibility to the disease. Individuals carrying susceptibility genes are frequently at very high risk of developing cancer that is often diagnosed at an early age. Study of this group of people is important for two major reasons:

•Identification of individuals who are at high risk before they develop the disease may allow them to take avoiding action
•Elucidation of the genetic mechanisms underlying the susceptibility often generates important insights into the development of the common forms of non-familial cancer
Within the last few years the availability of new technologies to investigate the whole genome in substantial numbers of cases has allowed expansion of our research to investigation of genetic variants with smaller increases in cancer risk, at a population level. Although the risks associated with such genetic variants are much smaller, they are often present in many people and can therefore be making an appreciable contribution to cancer. Major advances in the discovery of this class of predisposition gene are anticipated over the next few years.

The Section of Cancer Genetics includes research programmes studying predisposition to a wide range of adult cancers, including breast cancer, colorectal cancer, prostate cancer, testis cancer, thyroid cancer and leukaemia. In addition, we have one of the few research programmes investigating predisposition to childhood cancers. These programmes range from mapping and identifying the genes responsible, through characterisation and evaluation of their importance, to the implementation of the findings in the clinic.

The Cancer Genome Project was established by Professor Mike Stratton and Dr Richard Wooster at the Wellcome Trust Sanger Institute at Hinxton. The availability of the finished human genome sequence provided the platform from which the systematic search for somatically acquired abnormalities in DNA of cancer cells could be launched. The close collaboration between the Wellcome Trust Sanger Institute and The Institute enables both Institutions to maximise their contributions to a major medical research aim of the next decade: the exploitation of the human genome sequence in cancer research.



Recent Highlights

Breast Cancer: In 2006 we reported three breast cancer predisposition genes, ATM, BRIP1 and PALB2. Mutations in these genes are rare in the UK population and double the risk of breast cancer. The genes all act in pathways that repair damaged DNA and interact with the known breast cancer genes BRCA1 or BRCA2.

Childhood Cancer: In 2006 we also showed that very rare individuals with two (biallelic) mutations in PALB2 develop a serious childhood development disorder known as Fanconi anemia and have a very high risk of childhood cancer. Biallelic mutations in two other breast cancer genes, BRCA2 and BRIP1, have also been shown to lead to subtypes of Fanconi anaemia.

Prostate Cancer: 2006 saw the start of a large, unique international study of targeted screening for prostate cancer in men with an increased risk of the disease – the IMPACT study.

Colorectal Cancer: In 2006 we reported a new susceptibility locus for colorectal cancer on chromosome 3q21. We also reported the results of a large-scale genome-wide association study of nonsynonymous single nucleotide polymorphisms which suggests that variants in the GH-IGF and DNA damage response pathways may influence disease risk.