Multiple functional variants in long-range enhancer elements contribute to the risk of SNP rs965513 in thyroid cancer

Papillary thyroid carcinoma (PTC) displays a strong hereditary component that is, in part, due to the additive effects of numerous low-penetrance genes or variants, but virtually no mechanistic information is available. Here, we studied a well-known low-penetrance variant (SNP rs965513) located in a region devoid of coding genes. We show that at least four variants located in the immediate vicinity of rs965513 reside in enhancer elements that bind to the promoter region shared by two adjacent thyroid-related genes, forkhead box E1 ( ) and PTC susceptibility candidate 2 ( ), regulating their expression. The role of intergenic regulatory variants in cancer predisposition and carcinogenesis is growing. Further mechanistic understanding of how these variants work such as described here needs to be acquired.

Duke Scholars

Author Qianben Wang Pathology