Of the four loci associated with primary tooth development in Pillas et al. (6) and confirmed in this study, three have known developmental functions: KCNJ2, EDA and IGF2BP1. The link between normal development and cancer has been noted previously (48), with both involving shifts between cell proliferation and differentiation. Five of the 15 loci identified by our study have been implicated in cancer. As noted earlier, rare mutations in RAD51C have been implicated in breast and ovarian cancer. Likewise, a variant in BMP4 has been found to be associated with colorectal cancer; also a variant in 2q35 has been found to be associated with breast cancer. In both cases, the reported SNP is in high LD with the lead SNP at the respective locus in our study and was also associated with primary tooth eruption. However, whereas the allele associated with increased risk of colorectal cancer was associated with earlier time to tooth eruption, the allele associated with increased risk of breast cancer was associated with fewer teeth at 12 months. Expression of HMGA2 has been implicated in bladder and
