Researchers identified a variant that confers susceptibility to BCCs and other cancers.


Based on the presence of mutations found in sporadic basal cell carcinoma (BCC) and those arising in the context of basal cell nevus (Gorlin) syndrome, researchers have established TP53, PTCH1, PTCH2, and SUFU as important susceptibility genes in BCC pathogenesis. To identify new risk variants for cutaneous BCC, investigators performed a genome-wide association study (GWAS) using 16 million single-nucleotide polymorphisms identified through the DNA sequencing of 457 Icelanders.

The strongest association with BCC risk (odds ratio = 2.36) was with a polymorphism in the polyadenylation sequence of TP53. Polyadenylation (the addition of adenines to the ends of messenger RNA [mRNA] transcripts) promotes transport and stability, thus enhancing translation. Affected cells made slightly less TP53 mRNA transcript than wild-type cells, and proper termination of the TP53 transcript was disrupted with this variant. Using multiple validation sets, the researchers also associated this variant with increased risk for colorectal adenoma (OR = 1.39), prostate cancer (OR = 1.44), and glioma (OR = 2.35).


Citation(s):

Stacey SN et al. A germline variant in the TP53 polyadenylation signal confers cancer susceptibility. Nat Genet 2011 Sep 25; 43:1098.