The influence of common polymorphisms on breast cancer.

Breast cancer is one of the most frequently diagnosed cancers in the Western world and a significant cause of mortality worldwide. A small proportion of cases are accounted for by high-penetrance monogenic predisposition genes; however, this explains only a small fraction (less than 5%) of all breast cancers. Increasingly with advances in molecular technology and the development of large research consortia, the locations and identities of many low-penetrance genetic variants are being discovered. However, each variant has a very small effect similar to or smaller than many of the known environmental risk factors. It is therefore unlikely that these variants will be appropriate for predictive genetic testing, although they may identify novel pathways and genes which provide new insights and targets for therapeutic intervention. The future challenges will be identifying causal variants and determining how these low-penetrance alleles interact with each other and with environmental factors in order to usefully implement them in the practice of clinical medicine. Furthermore, it is clear that breast cancer comes in many forms with the tumour pathology and immunohistochemical profile already being used routinely as prognostic indicators and to inform treatment decisions. However, these indicators of prognosis are imperfect; two apparently identical tumours may have very different outcomes in different individuals. Inherited genetic variants may well be one of the other factors that need to be taken into account in assessing prognosis and planning treatment.