MALAT1 rs619586 A/G polymorphisms are associated with decreased risk of lung cancer

Abstract

Lung cancer is the leading cause of cancer-associated mortality worldwide. Genetic factors are reported to play important roles in lung carcinogenesis. To evaluate genetic susceptibility, we conducted a hospital-based case-control study on the effects of functional single nucleotide polymorphisms (SNPs) in long non-coding RNAs (lncRNAs) and microRNAs on lung cancer development. A total of 917 lung cancer cases and 925 control subjects were recruited. The MALAT1 rs619586 A/G genotype frequencies between patient and control groups were significantly different (P < .001), specifically, 83.85% vs 75.88% (AA), 15.60% vs 21.79% (AG), and 0.55% vs 2.32% (GG). When the homozygous genotype MALAT1 rs619586 AA was used as the reference group, AG (AG vs AA: adjusted odds ratio [OR] 0.65, 95% confidential interval [CI] 0.51-0.83, P = .001) and GG genotypes were associated with significantly decreased risk of lung cancer (GG vs AA: adjusted OR 0.22, 95% CI 0.08-0.59, P = .003). In the dominant model, MALAT1 rs619586 AG/GG variants were also associated with a significantly decreased risk of lung cancer (adjusted OR 0.61, 95% CI 0.48-0.78, P < .001). In the recessive model, when MALAT1 rs619586 AA/AG genotypes were used as the reference group, the GG homozygous genotype was also associated with significantly decreased risk for lung cancer (adjusted OR 0.24, 95% CI 0.09-0.64, P = .004). Hsa-miR-34b/c rs4938723 T > C, pri-miR-124-1 rs531564 C > G and hsa-miR-423 rs6505162 C > A SNPs were not associated with lung cancer risk. Our collective data indicated that MALAT1 rs619586 A/G SNPs significantly reduced the risk of lung cancer. Large-scale studies on different ethnic populations and tissue-specific biological characterization are required to validate the current findings.