State Key Laboratory of Medical Genomics, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
PLoS One. 2012;7(6):e39814. doi: 10.1371/journal.pone.0039814. Epub 2012 Jun 25.
Lung cancer is the most common cause of cancer-related deaths worldwide. The aim of this study was to investigate the association of five extensively-studied polymorphisms in PTGS2 (rs689466, rs5275, rs20417) and CYP2E1 (rs2031920, rs6413432) genes with lung cancer risk in a large northeastern Chinese population.
METHODOLOGY/PRINCIPAL FINDINGS: This is a hospital-based case-control study involving 684 patients with lung cancer and 604 cancer-free controls. Genotyping was performed using the PCR-LDR method. Data were analyzed using Haplo.stats and MDR programs. There were significant differences between patients and controls in allele/genotype distributions of rs5275 (P = 0.002/0.003) and rs6413432 (P = 0.037/0.044), as well as in genotype distributions of rs689466 (P = 0.02). The risk for lung cancer associated with the rs5275-C mutant allele was decreased by 60% (95% CI [confidence interval]: 0.21-0.74; P = 0.004) under the recessive model. Carriers of rs689466-G mutant allele had a 28% (95% CI: 0.57-0.92; P = 0.008) reduced risk of developing lung cancer relative to the AA genotype carriers. In haplotype analysis, haplotype G-C-C-T (in order of rs689466, rs5275, rs2031920 and rs6413432) decreased the odds of lung cancer by 28% (95% CI: 0.51-0.93; P = 0.019) after adjusting for confounding factors, whereas haplotype A-T-T-T had 1.49-fold (95% CI: 1.21-1.79; P = 0.012) increased risk for lung cancer. Using MDR method, the overall best model including rs5275, rs689466 and rs6413432 polymorphisms was identified with a maximal testing accuracy of 66.1% and a maximal cross-validation consistency of 10 out of 10 (P = 0.003).
CONCLUSIONS/SIGNIFICANCE: Our findings demonstrated a potentially synergistic association of PTGS2 and CYP2E1 polymorphisms with the underlying cause of lung cancer in northeastern Chinese.
肺癌是全球癌症相关死亡的最常见原因。本研究旨在探讨在一个大型中国东北地区人群中，PTGS2（rs689466、rs5275、rs20417）和 CYP2E1（rs2031920、rs6413432）基因的五个广泛研究的多态性与肺癌风险的关联。
方法/主要发现：这是一项基于医院的病例对照研究，涉及 684 名肺癌患者和 604 名无癌症对照者。采用 PCR-LDR 法进行基因分型。使用 Haplo.stats 和 MDR 程序进行数据分析。rs5275（P=0.002/0.003）和 rs6413432（P=0.037/0.044）的等位基因/基因型分布以及 rs689466 的基因型分布（P=0.02）在患者和对照组之间存在显著差异。在隐性模型下，rs5275-C 突变等位基因与肺癌风险降低 60%（95%CI[置信区间]：0.21-0.74；P=0.004）。与 AA 基因型携带者相比，rs689466-G 突变等位基因携带者患肺癌的风险降低 28%（95%CI：0.57-0.92；P=0.008）。在单倍型分析中，单倍型 G-C-C-T（按 rs689466、rs5275、rs2031920 和 rs6413432 的顺序）在调整混杂因素后，肺癌的比值比降低 28%（95%CI：0.51-0.93；P=0.019），而单倍型 A-T-T-T 则使肺癌的风险增加 1.49 倍（95%CI：1.21-1.79；P=0.012）。使用 MDR 方法，确定了包括 rs5275、rs689466 和 rs6413432 多态性在内的总体最佳模型，其最大检测准确率为 66.1%，最大交叉验证一致性为 10 次中的 10 次（P=0.003）。
结论/意义：我们的研究结果表明，PTGS2 和 CYP2E1 多态性与中国东北地区肺癌的潜在病因之间存在协同关联。
