Polymorphisms in alternative splicing associated genes are associated with lung cancer risk in a Chinese population

Alternative splicing is an important biological step during mRNA processing. Misregulation of alternative splicing can produce aberrant protein isoforms, thus contributing to cancer. We hypothesized that variants in 5 critical splicing factor-associated genes might play an important role in carcinogenesis of lung cancer.

A case-control study including 1,341 non-small cell lung cancer (NSCLC) cases and 1,982 cancer-free controls were conducted to evaluate the associations of 16 tagging/functional polymorphisms in 5 splicing factor-associated genes with lung cancer risk.

We found altogether 8 SNPs were associated with lung cancer risk with adjustment of age, gender, and smoking status after multiple corrections (FDR). Among these, six SNPs were related with SRSF7(rs10197412, OR (95% CI)=1.23 (1.06-1.43), P for FDR=0.018; rs12621103, OR(95% CI)=1.25 (1.08-1.46), P for FDR=0.016; rs13024811, OR (95% CI)=1.25 (1.07-1.46), P for FDR=0.016; rs2037875, OR (95% CI)=1.23 (1.06-1.42), P for FDR=0.018; rs3134628, OR (95% CI)=1.25(1.07-1.45), P for FDR=0.016 and rs6715866, OR (95% CI)=1.23 (1.07-1.43), P for FDR=0.016); one SNP was near PTBP2 (rs12566237: OR (95% CI)=1.16 (1.05-1.28), P for FDR=0.016) and one SNP in HNRNPQ (rs16876385: OR (95% CI)=1.17 (1.04-1.32), P for FDR=0.022).

Our findings indicated that genetic variants in these splicing-associated genes might modify individual susceptibility to lung cancer in Chinese population. Further large-scale well-formed population studies and functional researches are warranted to confirm our findings.