Genetic association of NEAT1 gene polymorphism with the progression of colorectal cancer

Colorectal cancer (CRC) is a globally common malignancy, whose complex disease etiology involves a genetic element. <i>Nuclear enriched abundant transcript 1</i> (<i>NEAT1</i>), a long noncoding RNA (lncRNA) gene, has been demonstrated to play a key role in cancer development. To clarify the potential effect of <i>NEAT1</i> gene polymorphisms on CRC susceptibility, three <i>NEAT1</i> single-nucleotide polymorphisms (SNPs), including rs3825071, rs3741384, and rs512715, were assessed in 485 CRC patients and 485 sex- and age-matched non-cancer controls. We did not detect any significant association of these SNPs with the occurrence and clinicopathological features of CRC. Nevertheless, one SNP of <i>NEAT1</i> gene, rs3825071, was found in association with the distant metastasis (CT+TT: CC, OR, 2.644; 95% CI, 1.328-5.263; p=0.005) among relatively younger patients (< 65 years old), indicating an age-specific effect of <i>NEAT1</i> gene polymorphisms on the spread of CRC. Our stratification analysis revealed that the association of rs3825071 with CRC metastasis is anatomical site-specific, as cases of colon tumors but not of rectal tumors who bear at least one polymorphic allele of rs3825071 more commonly developed metastasis. Further exploration using the datasets from the Genotype-Tissue Expression (GTEx) Portal and The Cancer Genome Atlas (TCGA) showed that rs3825071 genotypes affected NEAT1 expression in the colon tissues, and elevated NEAT1 levels were associated with a worse survival rate in relatively younger patients (< 65 years old) with colon adenocarcinoma. These data suggest that altered expression levels of NEAT1 due to genetic polymorphisms may influence the progression of colon cancer.