As we geared up to identify the risks associated with candidate genes, it became evident that individual studies were not making as much headway as we would like. Many studies were underpowered and a disconcerting number of published associations turned out to be false-positives. It was obvious that we needed very large scale, multi-center studies in the form of consortia that involved existing case controlling cohort studies. It took a while to develop the consortium but they now provide a platform for replication strategies to rapidly confirm positive associations in independent datasets, and for pooling strategies with the statistical power to identify the low to moderate risks from gene variants, exposures, and their interactions. These initiatives were possible because of a collaborative spirit and a coordinated plan involving intramural and extramural epidemiologists, as well as a close working relationship with genomicists and with extramural program staff at NCI, especially in the Division of Cancer Control and Population Sciences.