Department of Molecular and Genetic Toxicology, Jiangsu Key Laboratory of Cancer Biomarkers, Prevention and Treatment, Cancer Center, School of Public Health, Nanjing Medical University, Nanjing 210029, China.
J Gastroenterol. 2011 Nov;46(11):1260-6. doi: 10.1007/s00535-011-0445-3. Epub 2011 Aug 12.
Two genome-wide association studies on gastric cancer showed a previously unknown gastric cancer susceptible locus in PLCE1 at 10q23. We hypothesized that the single nucleotide polymorphism (SNP) rs2274223 A/G is associated with the survival rate of gastric cancer.
We genotyped the above SNP in 940 gastric cancer patients to investigate the association between the polymorphism and gastric cancer survival by the TaqMan method.
We found that patients carrying PLCE1 rs2274223 AA genotype survived for a significantly shorter time than those carrying the AG and GG genotypes (log-rank P = 0.046). This significance was enhanced in the dominant model (AA vs. AG/GG, log-rank P = 0.014). Multivariate Cox regression analyses showed that the AG/GG genotypes were associated with a significantly decreased risk of death from gastric cancer [adjusted hazard ratio (HR) = 0.79, 95% confidence interval (CI) = 0.65-0.95]. Most of stratification analysis did not find an enhanced association between the same genotype and prognosis, except for patients with TNM stage III disease (HR = 0.63, 95% CI = 0.48-0.83).
Our findings showed that the PLCE1 SNP rs2274223 was associated with significantly improved gastric cancer survival in a Chinese population. Further functional studies are needed to validate our results.
两项关于胃癌的全基因组关联研究显示,在 10q23 上的 PLCE1 中存在一个以前未知的胃癌易感基因座。我们假设单核苷酸多态性(SNP)rs2274223 的 A/G 与胃癌的生存率有关。
我们使用 TaqMan 方法对 940 名胃癌患者进行了上述 SNP 的基因分型,以研究该多态性与胃癌生存率之间的关系。
我们发现携带 PLCE1 rs2274223 AA 基因型的患者的生存时间明显短于携带 AG 和 GG 基因型的患者(对数秩检验 P = 0.046)。这种显著性在显性模型中得到增强(AA 与 AG/GG,对数秩检验 P = 0.014)。多变量 Cox 回归分析表明,AG/GG 基因型与胃癌死亡风险显著降低相关[调整后的危险比(HR)= 0.79,95%置信区间(CI)= 0.65-0.95]。除了 TNM 分期为 III 期的患者(HR = 0.63,95%CI = 0.48-0.83)外,大多数分层分析并未发现相同基因型与预后之间的关联增强。
我们的研究结果表明,在中国人群中,PLCE1 SNP rs2274223 与胃癌生存率的显著改善相关。需要进一步的功能研究来验证我们的结果。