Genetic variations in DROSHA and DICER and survival of advanced non-small cell lung cancer: a two-stage study in Chinese population

Abstract

MicroRNAs (miRNA) are a class of small, noncoding RNA molecules involved in carcinogenesis. Genetic variations in miRNA processing genes may affect the biogenesis of miRNAs, and consequently affect miRNAs regulation and development and progression of human cancer. Therefore, we hypothesized that polymorphisms in two main miRNA biosynthesis genes (DROSHA and DICER) may modulate the survival of advanced non-small cell lung cancer (NSCLC) patients in China. We selected 36 common tagging SNPs in DROSHA and DICER and evaluated the associations of these SNPs with survival of advanced NSCLC patients by a two-stage study in Chinese Han population (discovery cohort: 303 patients; replication cohort: 340 patients). Thirty-six SNPs were detected in the discovery cohort and 12 promising SNPs were validated in the replication cohort. The results showed that DROSHA rs3805525 was marginally associated with the survival of NSCLC patients in the replication cohort (dominant model: HR 0.69, 95 % CI 0.46–1.03, P = 0.071), which was in the same direction as that in the discovery cohort. When combing all patients into one group, three SNPs (rs3805525, rs17410035 and rs7719497) in DROSHA showed significantly associations with NSCLC survival (additive model: HR 0.82, 95 % CI 0.68–0.99 for rs3805525; HR 0.79, 95 % CI 0.62–1.00 for rs17410035; HR 0.76, 95 % CI 0.62–0.93 for rs7719497). Additionally, the combined analysis of those three SNPs showed a significant locus-dosage effect between number of favorable alleles and death risk of NSCLC (Trend P = 0.002). Genetic variations in DROSHA might be associated with the survival of advanced NSCLC patients in Chinese population.