RB1 and cancer: For example, the polymorphism rs6983267 linked to colorectal (Tomlinson et al., 2007) and prostate (Yeager et al., 2007) cancers contributes more to cancer morbidity and mortality than any other known inherited variant or mutation, including the inherited mutations in classic tumor suppressors such as RB, TP53 and APC. Through computational and experimental analyses, we and others have shown that the risk allele G of rs6983267 creates a strong binding site for the colorectal-cancer associated transcription factor Tcf7l2 (Pomerantz et al., 2009; Tuupanen et al., 2009).