Functional miRNA variants affect lung cancer susceptibility and platinum-based chemotherapy response

Background: Platinum-based chemotherapy is widely used as the first-line treatment of lung cancer. MicroRNAs have an important role in lung carcinogenesis and progression. Single-nucleotide polymorphisms (SNPs) in miRNA involved in miRNA biogenesis and structural alteration may affect miRNA expression. In this study, we aimed to investigate the association of functional miRNA variants with the lung cancer susceptibility and platinum-based chemotherapy response. Methods: Nine genetic polymorphisms in miR-605, 146a, 149, 196a-2, 27a, 499, 30c-1, 5197 and let-7a-2 were selected with comprehensive collection strategy and genotyped by MALDI-TOF mass spectrometry in a total of 215 health control and 507 lung cancer patients (386 patients received at least two consecutive cycles of platinum-based chemotherapy). Results: We found that an allele carriers of miR-146a rs2910164 (P=0.022, OR=1.315) and C allele carriers of miR-149 rs71428439 (P=0.042, OR=1.372) performance a high risk of lung cancer. Mir-30c-1 rs928508 (P=0.005, in recessive model) and let-7a-2 rs629367 (P=0.030 and P=0.021, in additive and dominant models, respectively) showed strong relationship with lung cancer risk in age under 57 years. The rs11614913 (miR-196a-2) C allele or rs9280508 (miR-30c-1) G allele carriers shown more sensitive to platinum both in additive (P=0.010, P=0.022, respectively) and dominant models (P=0.001, P=0.018, respectively). Conclusions: These findings suggested that SNPs rs71428439 (miR-149), rs2910164 (miR-146a), rs928508 (mir-30c-1) and rs629367 (let-7a-2) were associated with the lung cancer prevalence, polymorphisms of rs11614913 (miR-196a-2) and rs9280508 (miR-30c-1) significantly influenced the patients’ response to platinum-based chemotherapy, which may serve as potential clinical biomarkers to predict lung cancer risk and platinum-based chemotherapy response.