TP53 and brain cancer: Indeed, SNPs in well-described p53 pathway genes have been frequently identified in GWASs of seemingly sporadic cancers.18 In fact, one p53 pathway SNP, MDM2 SNP309 that associates with differential expression levels of a key regulator of p53, has been shown to modify cancer risk in TP53 mutation carriers with LFS.22 Specifically, LFS families with more penetrant TP53 mutations relative to the Brazilian R337H, are at higher risks of developing many types of cancer, such as sarcomas, breast, and brain cancers, as well as ACC.