Metastasis associated with lung adenocarcinoma transcript-1 (MALAT1) is an evolutionarily highly conserved lncRNA that contributes to colorectal cancer development. However, the exact molecular mechanisms connecting MALAT1 to colorectal cancer have not been fully elucidated. Here, we performed a case-control study in 1,078 patients with colorectal cancer and 1,175 healthy controls to evaluate the association between potentially functional genetic variants of MALAT1 and survival outcomes in patients with colorectal cancer. MALAT1 rs664589 CG/GG genotypes significantly increased the associated risk and decreased overall survival of patients with colorectal cancer compared with the CC genotype. In vitro and in vivo experiments showed that the rs664589 C to G mutation facilitated carcinogenesis and metastasis of colorectal cancer. Mechanistically, the miRNA miR-194-5p targeted MALAT1 for degradation in the nucleus in an Ago2-dependent manner; the rs664589 G allele altered the binding of MALAT1 to miR-194-5p, resulting in increased expression of MALAT1. Colorectal cancer cells and human tissues with the rs664589 CG/GG genotype expressed significantly higher MALAT1 than those with the rs664589 CC genotype. Multivariate Cox regression analysis showed that MALAT1 was a poor prognostic factor of colorectal cancer. In summary, MALAT1 with the rs664589 G allele demonstrates altered binding to miR-194-5p in the nucleus, leading to increased MALAT1 expression and enhanced colorectal cancer development.Significance: These findings highlight the functional role of MALAT1 polymorphism in colorectal cancer metastasis and survival as well as the underlying mechanism.

Gastric cardiac adenocarcinoma (GCA) is one of common malignant tumors in the world. Multiple genes that play critical roles in inflammatory pathways probably are associated with GCA risk. We conducted a hospital-based case-control study to evaluate the genetic effects of functional single nucleotide polymorphisms (SNPs): interleukin 9 (IL9) rs31563 C > T, IL9 rs31564 G > T, IL10 rs1800872 T > G, IL12A rs2243115 T > G, IL12B rs3212227 T > G, and IL13 rs1800925 C > T on the development of GCA. Two hundred and forty-three GCA cases and 476 controls were recruited. Their genotypes were determined using a custom-by-design 48-Plex SNPscan kit. IL12B rs3212227 T > G polymorphism was associated with the increased risk of GCA. However, there was no significant association between the other five SNPs and GCA risk. Stratified analyses indicated that the risk of GCA associated with the IL12B rs3212227 T > G polymorphism was evident among female patients and patients who never smoked or consumed alcoholic drinks. These findings indicated that functional polymorphism IL12B rs3212227 T > G might correlate with GCA risk. However, our results were obtained with a limited sample size; the power of our analysis was low. Larger studies are required to confirm the current findings.

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