A novel SNP in promoter region of RP11-3N2.1 is associated with reduced risk of colorectal cancer

J Hum Genet. 2018 Jan;63(1):47-54. doi: 10.1038/s10038-017-0361-3. Epub 2017 Oct 5.

Abstract

Single-nucleotide polymorphisms (SNPs) in the promoter region of long intergenic non-coding RNAs (lincRNAs) could play a regulatory role in its expression level and then get involved in colorectal cancer (CRC). Thus, we conducted a two-stage case-control study to investigate the associations of Tag SNPs within the promoter region of selected lincRNAs from microarray data with risk of CRC. A total of 320 cases and 319 controls were recruited in the test set to explore the associations between 16 SNPs with no deviations from Hardy-Weinberg equilibrium (HWE) and risk of CRC. Furthermore, 501 cases and 538 controls were included as the validation set to confirm the significant associations. RP11-3N2.1 rs13230517 polymorphism was found to be negatively associated with CRC in both test set (AA vs. GG, OR = 0.68, 95% CI = 0.48-0.96) and validation set (AA vs. GG, OR = 0.76, 95% CI = 0.59-0.98). Pooled analysis showed that individuals with GA/AA genotypes had a significantly decreased risk of CRC when compared with those carrying GG genotype (OR = 0.74, 95% CI = 0.60-0.90) in the combined set. The crossover analysis revealed that rs13230517 GA/AA carriers had a decreased risk of CRC than GG carriers among non-drinkers in both test and combined set. However, no gene-environment multiplicative interactions were found on risk of CRC. Our findings suggest that rs13230517 polymorphism might participate in the pathogenesis of CRC and have the potential to be a biomarker for predicting the risk of CRC.

MeSH terms

  • Aged
  • Biomarkers, Tumor / biosynthesis
  • Biomarkers, Tumor / genetics*
  • Case-Control Studies
  • Colorectal Neoplasms / genetics*
  • Colorectal Neoplasms / metabolism
  • Female
  • Genotype*
  • Humans
  • Male
  • Middle Aged
  • Polymorphism, Single Nucleotide*
  • Promoter Regions, Genetic*
  • RNA, Long Noncoding / biosynthesis
  • RNA, Long Noncoding / genetics*
  • RNA, Neoplasm / biosynthesis
  • RNA, Neoplasm / genetics*
  • Risk Factors

Substances

  • Biomarkers, Tumor
  • RNA, Long Noncoding
  • RNA, Neoplasm