title: Genetic Variation in the 3'-Untranslated Region of NBN Gene Is Associated with Gastric Cancer Risk in a Chinese Population.
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.
authors.affiliation: Department of General Surgery, the Second Affiliated Hospital of Soochow University, Suzhou 215004, China; Department of Pathology, Nanjing Medical University Affiliated Wuxi Second Hospital, Wuxi 214006, China.
authors.forename: Ping
authors.initials: P
authors.lastname: Sun
authors.affiliation: Department of Epidemiology and Biostatistics, School of Public Health, Nanjing Medical University, Nanjing 211166, China; Jiangsu Key Lab of Cancer Biomarkers, Prevention and Treatment, Collaborative Innovation Center For Cancer Personalized Medicine, Nanjing Medical University, Nanjing 211166, China.
authors.forename: Jiangbo
authors.initials: J
authors.lastname: Du
authors.affiliation: Department of Epidemiology and Biostatistics, School of Public Health, Nanjing Medical University, Nanjing 211166, China.
authors.forename: Xun
authors.initials: X
authors.lastname: Zhu
authors.affiliation: Medical Lab, Northern Jiangsu People's Hospital, Yangzhou 225001, China.
authors.forename: Chuanli
authors.initials: C
authors.lastname: Ren
authors.affiliation: Medical Systems Biology Research Center, Tsinghua University School of Medicine, Beijing 100084, China.
authors.forename: Lan
authors.initials: L
authors.lastname: Xie
authors.affiliation: Department of Epidemiology and Biostatistics, School of Public Health, Nanjing Medical University, Nanjing 211166, China; Jiangsu Key Lab of Cancer Biomarkers, Prevention and Treatment, Collaborative Innovation Center For Cancer Personalized Medicine, Nanjing Medical University, Nanjing 211166, China.
authors.forename: Ningbin
authors.initials: N
authors.lastname: Dai
authors.affiliation: Department of Epidemiology and Biostatistics, School of Public Health, Nanjing Medical University, Nanjing 211166, China; Jiangsu Key Lab of Cancer Biomarkers, Prevention and Treatment, Collaborative Innovation Center For Cancer Personalized Medicine, Nanjing Medical University, Nanjing 211166, China.
authors.forename: Yayun
authors.initials: Y
authors.lastname: Gu
authors.affiliation: Department of Epidemiology and Biostatistics, School of Public Health, Nanjing Medical University, Nanjing 211166, China.
authors.forename: Caiwang
authors.initials: C
authors.lastname: Yan
authors.affiliation: Department of Epidemiology and Biostatistics, School of Public Health, Nanjing Medical University, Nanjing 211166, China; Jiangsu Key Lab of Cancer Biomarkers, Prevention and Treatment, Collaborative Innovation Center For Cancer Personalized Medicine, Nanjing Medical University, Nanjing 211166, China.
authors.forename: Juncheng
authors.initials: J
authors.lastname: Dai
authors.affiliation: Department of Epidemiology and Biostatistics, School of Public Health, Nanjing Medical University, Nanjing 211166, China.
authors.forename: Hongxia
authors.initials: H
authors.lastname: Ma
authors.affiliation: Department of Epidemiology and Biostatistics, School of Public Health, Nanjing Medical University, Nanjing 211166, China.
authors.forename: Yue
authors.initials: Y
authors.lastname: Jiang
authors.affiliation: Department of Epidemiology and Biostatistics, School of Public Health, Nanjing Medical University, Nanjing 211166, China; Jiangsu Key Lab of Cancer Biomarkers, Prevention and Treatment, Collaborative Innovation Center For Cancer Personalized Medicine, Nanjing Medical University, Nanjing 211166, China.
authors.forename: Jiaping
authors.initials: J
authors.lastname: Chen
authors.affiliation: Department of Epidemiology and Biostatistics, School of Public Health, Nanjing Medical University, Nanjing 211166, China; Jiangsu Key Lab of Cancer Biomarkers, Prevention and Treatment, Collaborative Innovation Center For Cancer Personalized Medicine, Nanjing Medical University, Nanjing 211166, China.
authors.forename: Zhibin
authors.initials: Z
authors.lastname: Hu
authors.affiliation: Department of Epidemiology and Biostatistics, School of Public Health, Nanjing Medical University, Nanjing 211166, China; Jiangsu Key Lab of Cancer Biomarkers, Prevention and Treatment, Collaborative Innovation Center For Cancer Personalized Medicine, Nanjing Medical University, Nanjing 211166, China.
authors.forename: Hongbing
authors.initials: H
authors.lastname: Shen
authors.affiliation: Department of General Surgery, the Second Affiliated Hospital of Soochow University, Suzhou 215004, China.
authors.forename: Haorong
authors.initials: H
authors.lastname: Wu
authors.affiliation: Department of Epidemiology and Biostatistics, School of Public Health, Nanjing Medical University, Nanjing 211166, China; Jiangsu Key Lab of Cancer Biomarkers, Prevention and Treatment, Collaborative Innovation Center For Cancer Personalized Medicine, Nanjing Medical University, Nanjing 211166, China.
authors.forename: Guangfu
authors.initials: G
authors.lastname: Jin
mesh_terms: D020413:3' Untranslated Regions / Q000235:genetics*; D044466:Asian People / Q000235:genetics*; D016022:Case-Control Studies; D018797:Cell Cycle Proteins / Q000235:genetics*; D005260:Female; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease; D014644:Genetic Variation; D006239:Haplotypes / Q000235:genetics; D006801:Humans; D008297:Male; D008875:Middle Aged; D009687:Nuclear Proteins / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D012307:Risk Factors; D013274:Stomach Neoplasms / Q000235:genetics*
chemical_list: D020413:3' Untranslated Regions; D018797:Cell Cycle Proteins; C112156:NBN protein, human; D009687:Nuclear Proteins