Asbestos-Induced Lung Cancer-Associated SNP rs13383928 Regulates PTH2R Expression in Lung Tissue

Lung cancer is one of the most common malignant tumors, and asbestos exposure was suggested to contribute to a proportion of lung cancer cases. Previous genome-wide gene-environment interaction analysis reported that rs13383928 was associated with asbestos-related lung cancer. However, the mechanism of this association was still unclear.

In the present study, we retrieved the genotype data from the 1,000 Genomes Project on single-nucleotide polymorphisms (SNPs) surrounding rs13383928 and analyzed the linkage disequilibrium (LD) pattern of this region. Further functional genomics analyses were performed.

The result indicated that no other SNPs were in LD with rs13383928, suggesting that rs13383928 is the causal one. The following dual luciferase assay disclosed that the T allele of rs13383928 presented significantly higher enhancer activity than G in lung cells, thus verifying that this SNP was functional in the lung. Through chromosome conformation capture, the PTH2R (parathyroid hormone 2 receptor)promoter was identified to interact with the segment surrounding rs13383928. By chromatin immunoprecipitation, it was observed that the region spanning rs13383928 could bind transcription factor FOXJ2 (forkhead box J2).

Our functional genomics evidence supports a link between rs13383928 and asbestos-related lung cancer through regulating PTH2R.