Book of abstract 2008

Genetic predisposition on breast cancer – clinical perspectives
Malcolm Reed
Academic Unit of Surgical Oncology, School of Medicine and Biomedical Sciences, Beech Hill Road,
Sheffield, S10 2RX, UK
Breast cancer is a multi-factorial disease with a significant genetic predisposition. Despite
significant advances in the identification of ‘high penetrant’ genes and their routine
clinical application to individuals with a ‘strong’ family history, many genetic variants
making a mild to moderate contribution to risk remain uncharacterised. It is well
recognised that a substantial contribution to the risk of many common multi-factorial
genes is from commonly occurring genetic variants which interact with each other or with
environmental factors. International collaborations such as the ‘Breast Cancer Association
Consortium’ (BCAC) are underway to pool efforts and resources in an attempt to unravel
the tangled web of genetic, gene-gene and gene-environment interactions that contribute
to disease predisposition.
This talk will discuss the evolution of a large population association genetic epidemiology
project in Sheffield (Sheffield Breast Cancer Study), which has now become part of
the Breast Cancer Association Consortium (BCAC). The key results including the
identification of several gene polymorphisms as ‘low to moderate’ susceptibility genes
and the relevance of these findings to the breast cancer clinician will be discussed. The
limitations to this approach include the risk of false positive results and the difficulty
in immediate application to clinical practice. However, the ability to improve risk
stratification and the increased insight into the molecular pathways that may yield further
targets for anti-cancer treatment is promising. Close collaboration between clinicians and
scientists are vital to the formulation of specific clinical questions, design and conduct of
such studies and the translation of findings to the bedside.
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