Genetic variant in 8q24 is associated with prognosis for gastric cancer in a Chinese population

J Gastroenterol Hepatol. 2015 Apr;30(4):689-95. doi: 10.1111/jgh.12801.

Abstract

Background and aim: Single nucleotide polymorphisms (SNPs) located in long noncoding RNA CASC8 gene may influence the process of splicing and stability of messenger RNA conformation, resulting in the modification of its interacting partners. Genome-wide association studies have identified the SNP rs10505477 and SNP rs1562430 in CASC8 were associated with risk of the colorectal cancer (CRC) and breast cancer, respectively.

Methods: In the present study, we genotyped the 940 surgically resected gastric cancer patients to explore the association between these two SNPs (e.g., rs10505477 and rs1562430) and survival of gastric cancer in a Chinese population.

Results: We found that the patients carrying rs10505477 GG genotype survived for a longer time than those with the GA and AA genotypes (log-rank P = 0.030). The similar result was also found in the dominant model (GA/AA vs GG, HR = 1.32, 95% CI = 1.08-1.63, log-rank P = 0.008). This risk effect was more pronounced among patients with tumor size ≤ 5 cm, diffuse-type gastric cancer, lymph node metastasis, no distant metastasis, and TNM stage III and IV. Furthermore, the area under the curve at five years was dramatically increased from 0.619 to 0.624 after adding the rs10505477 risk score to the traditional clinical risk score (TNM stage and lymph node metastasis). However, there was no association be found between the rs1562430 and the survival of gastric cancer.

Conclusion: These findings suggested the SNP rs10505477 may contribute to the survival of gastric cancer and be a potential prognostic biomarker of gastric cancer.

Keywords: gastric cancer; genetic variation; molecular epidemiology; survival.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Asian People / genetics*
  • Chromosomes, Human, Pair 8 / genetics*
  • Genome-Wide Association Study*
  • Humans
  • Lymphatic Metastasis
  • Neoplasm Staging
  • Polymorphism, Single Nucleotide / genetics*
  • Prognosis
  • RNA Splicing / genetics
  • RNA Stability / genetics
  • RNA, Long Noncoding / genetics*
  • RNA, Messenger / genetics
  • Risk
  • Stomach Neoplasms / genetics*
  • Stomach Neoplasms / mortality
  • Stomach Neoplasms / pathology
  • Survival Rate

Substances

  • RNA, Long Noncoding
  • RNA, Messenger