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. Nuclear enriched abundant transcript 1 (NEAT1), a long noncoding RNA (lncRNA) gene, has been demonstrated to play a key role in cancer development. To clarify the potential effect of NEAT1 gene polymorphisms on CRC susceptibility, three NEAT1 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 NEAT1 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 NEAT1 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.