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

BACKGROUND: 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. METHODS: 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. RESULTS: 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). CONCLUSION: Our functional genomics evidence supports a link between rs13383928 and asbestos-related lung cancer through regulating PTH2R.