Genetic predisposition to breast and prostate cancer

Gilles Thomas, Synergie-Lyon-Cancer.

Genome-wide association studies (GWAS) provide a powerful approach to identify common, low-penetrance disease loci without prior knowledge of location or function. This identification offers the potential for increased understanding of the basic biological processes affecting human health and for improvement in the prediction of disease risk. GWAS are enterprises requiring large amounts of resources and present significant analytical challenges. To date GWAS studies for breast or prostate cancer predisposition have led, for each tumor type, to the identification of over 10 different susceptibility loci dispersed throughout the genome. Many of these loci were detected at low power, suggesting that additional loci should be found with larger studies. Occasionally, associated markers may be located within genes with strong priors for being involved in carcinogenesis. However, most markers fail to identify unambiguously a specific gene. Some markers may even locate in gene deserts, demonstrating unsuspected disease mechanisms that remain to be elucidated. The odds ratio conferred by the risk alleles are small, generally 1.3 or less. Most individuals in the population carry multiple risk alleles that are distributed over many different chromosome regions. Conspicuous interaction between these loci in determining individual's cancer risk has not been evidenced but more discreet interaction may not be excluded. Carefully designed studies are warranted to determine how this knowledge may now be used in cancer prevention and early detection screening programs.