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.

MALAT1 Polymorphisms and Lung Cancer Susceptibility in a Chinese Northeast Han Population

“…MALAT1 rs619586 A>G has A protective effect on meningioma invasion by inhibiting the activation of collagen type V alpha (COL5A1) downstream gene 56 . A previous study showed that MALAT1 rs619586 polymorphism significantly reduced the risk of lung cancer 57 . But in this study, rs619586 and lung cancer were not statistically significant difference, the differences were found in many other diseases 33 , 35 , 37 - 39 , 44 .…”

PRNCR1: a long non-coding RNA with a pivotal oncogenic role in cancer

“…However, some PRNCR1 variants also showed association for decreased susceptibility to certain malignancies and this might be due to genetic variability specific to the ethnicity of the studied population and differential interaction of SNP genotypes with disease-specific risk factors. Similarly, genetic variants of other oncogenic lncRNAs like PCAT1 and MALAT1 were also found to be associated with decreased susceptibilities to bladder and lung cancers, respectively (Lin et al 2017 ; Chen et al 2021a ). PRNCR1 SNPs are located in exon-1 and are non-coding as the gene encodes for an lncRNA.…”