Genetic Variation in the 3'-Untranslated Region of NBN Gene Is Associated with Gastric Cancer Risk in a Chinese Population.
Genetic Variation in the 3'-Untranslated Region of NBN Gene Is Associated with Gastric Cancer Risk in a Chinese Population.
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NBN 基因 3'-非翻译区的遗传变异与中国人群胃癌风险相关
DOI：
10.1371/journal.pone.0139059
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发表时间：
2015
期刊：
影响因子：
3.7
通讯作者：
Jin G
中科院分区：
文献类型：
--
作者：
Sun P;Du J;Zhu X;Ren C;Xie L;Dai N;Gu Y;Yan C;Dai J;Ma H;Jiang Y;Chen J;Hu Z;Shen H;Wu H;Jin G
NBN作为同源重组（HR）和非同源末端连接（NHEJ）DNA双链断裂（DSB）修复途径的核心组分在致癌作用中起关键作用。NBN基因中的遗传变异与多种癌症风险相关，表明对癌症的多效性作用。我们假设NBN基因的遗传变异可能会改变胃癌的风险。为了验证这一假设，我们在中国人群中对1,140例胃癌病例和1,547例对照进行了病例对照研究，评估了NBN中4种潜在功能性单核苷酸多态性与胃癌风险之间的关联。我们发现rs 10464867的A等位基因（G>A）与胃癌风险降低显著相关（比值比[OR] = 0.81，95%置信区间[95% CI] = 0.71-0.94; P = 4.71×10−3）。此外，rs 10464867的A等位基因与胃癌风险降低之间的关联在老年个体（每个等位基因OR = 0.72[0.59-0.88]，P = 1.07×10−3）和男性个体（每个等位基因OR = 0.73[0.62-0.87]，P = 3.68×10−4）中更为显著。我们进一步进行了单倍型分析，发现NBN Ars 10464867 Grs 14448 Grs 1063053单倍型对胃癌具有更强的保护作用（OR = 0.76[0.65-0.89]，P = 6.39×10−4）。总之，这些研究结果表明，NBN基因的遗传变异可能有助于胃癌的易感性，并可能进一步提高我们对NBN基因在癌症发展中的认识。
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.