Genetic Variation in the 3'-Untranslated Region of NBN Gene Is Associated with Gastric Cancer Risk in a Chinese Population

PLoS One. 2015 Sep 24;10(9):e0139059. doi: 10.1371/journal.pone.0139059. eCollection 2015.

Abstract

NBN plays a crucial role in carcinogenesis as a core component for both homologous recombination (HR) and non-homologous end-joining (NHEJ) DNA double-strand breaks (DSBs) repair pathways. Genetic variants in the NBN gene have been associated with multiple cancers risk, suggesting pleiotropic effect on cancer. We hypothesized that genetic variants in the NBN gene may modify the risk of gastric cancer. To test this hypothesis, we evaluated the association between four potentially functional single nucleotide polymorphisms in NBN and gastric cancer risk in a case-control study of 1,140 gastric cancer cases and 1,547 controls in a Chinese population. We found that the A allele of rs10464867 (G>A) was significantly associated with a decreased risk of gastric cancer (odds ratio [OR] = 0.81, 95% confidence interval [95% CI] = 0.71-0.94; P = 4.71×10-3). Furthermore, the association between A allele of rs10464867 and decreased risk of gastric cancer was more significantly in elder individuals (per-allele OR = 0.72[0.59-0.88], P = 1.07×10-3), and male individuals (per-allele OR = 0.73[0.62-0.87], P = 3.68×10-4). We further conducted a haplotype analysis and identified that the NBN Ars10464867Grs14448Grs1063053 haplotype conferred stronger protective effect on gastric cancer (OR = 0.76[0.65-0.89], P = 6.39×10-4). In summary, these findings indicate that genetic variants at NBN gene may contribute to gastric cancer susceptibility and may further advance our understanding of NBN gene in cancer development.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 3' Untranslated Regions / genetics*
  • Asian People / genetics*
  • Case-Control Studies
  • Cell Cycle Proteins / genetics*
  • Female
  • Genetic Association Studies*
  • Genetic Predisposition to Disease*
  • Genetic Variation*
  • Haplotypes / genetics
  • Humans
  • Male
  • Middle Aged
  • Nuclear Proteins / genetics*
  • Polymorphism, Single Nucleotide / genetics
  • Risk Factors
  • Stomach Neoplasms / genetics*

Substances

  • 3' Untranslated Regions
  • Cell Cycle Proteins
  • NBN protein, human
  • Nuclear Proteins

Grants and funding

81230067, http://www.nsfc.gov.cn/, National Natural Science Foundation of China, HS; 81422042 and 81373090, http://www.nsfc.gov.cn/, National Natural Science Foundation of China, GJ; BK20130042, http://www.jstd.gov.cn/, Science and Technology Agency of Jiangsu Province, China, GJ; BL2012008, http://www.njkj.gov.cn/, Science and Technology committee of Nanjing, China, HS; http://www.jiangsu.gov.cn/, Government of Jiangsu Province, China, HS; Science Foundation for Distinguished Young Scholars in Jiangsu (BK20130042); Jiangsu Province Clinical Science and Technology Projects (Clinical Research Center, BL2012008); and Priority Academic Program for the Development of Jiangsu Higher Education Institutions (Public Health and Preventive Medicine). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.