Department of Epidemiology and Biostatistics, School of Public Health, Nanjing Medical University, Nanjing, China.
Jiangsu Key Lab of Cancer Biomarkers, Prevention and Treatment, Collaborative Innovation Center for Cancer Medicine, Nanjing Medical University, Nanjing, China.
J Hum Genet. 2018 Nov;63(11):1159-1168. doi: 10.1038/s10038-018-0501-4. Epub 2018 Sep 10.
Many features are shared between esophageal cancer (EC) and gastric cancer (GC). This study aimed to explore whether known EC susceptibility loci are also important in the development of GC. A total of 21 genetic variants associated with EC in genome-wide association studies were evaluated with association of GC risk in 2631 cases and 4373 controls of Chinese ancestry. Single variant and weighted genetic scores (WGS) for esophageal squamous cell carcinoma (ESCC), esophageal adenocarcinoma (EAC), and overall EC were analyzed with GC risk, respectively. Genetic variants of rs2274223 in PLCE1 at 10q23.33 (per G allele: odds ratio (OR) = 1.26, 95% confidence interval (CI): 1.16-1.38, P = 6.51 × 10), rs10052657 in PDE4D at 5q11.2 (per C allele: OR = 1.12, 95% CI: 1.01-1.25, P = 3.28 × 10) and rs671 in ALDH2 at 12q24.12 (per A-allele: OR = 0.83, 95% CI: 0.75-0.91, P = 1.14 × 10) were significantly associated with GC risk. The combined effect of those three variants had stronger influence on GC risk (OR = 1.31, 95% CI: 1.19-1.44, P = 2.34 × 10). High WGS of ESCC was also associated with increased risk of GC (P = 5.52 × 10 as a continuous variable) (trend test P = 2.71 × 10), whereas no statistically significant associations were observed between the WGS of EAC and GC risk (P = 0.66 as a continuous variable) (trend test P = 0.70). ESCC rather than EAC may share genetic susceptibility with GC. Genetic variants at 10q23.33, 5q11.2, and 12q24.12 may be useful as biomarkers to identify individuals with high risk for both ESCC and GC.
食管癌（EC）和胃癌（GC）有许多共同特征。本研究旨在探讨在 GC 发展过程中，已知的 EC 易感基因座是否也很重要。对来自中国的 2631 例病例和 4373 例对照进行了全基因组关联研究中与 EC 相关的 21 种遗传变异与 GC 风险的关联分析。分别分析了与 GC 风险相关的食管鳞状细胞癌（ESCC）、食管腺癌（EAC）和整体 EC 的单变体和加权遗传评分（WGS）。在 10q23.33 上的 PLCE1 中的 rs2274223 遗传变异（每 G 等位基因：比值比（OR）=1.26，95%置信区间（CI）：1.16-1.38，P=6.51×10）、在 5q11.2 上的 PDE4D 中的 rs10052657 遗传变异（每 C 等位基因：OR=1.12，95%CI：1.01-1.25，P=3.28×10）和在 12q24.12 上的 ALDH2 中的 rs671 遗传变异（每 A 等位基因：OR=0.83，95%CI：0.75-0.91，P=1.14×10）与 GC 风险显著相关。这三个变异的综合效应对 GC 风险的影响更强（OR=1.31，95%CI：1.19-1.44，P=2.34×10）。ESCC 的高 WGS 也与 GC 风险增加相关（作为连续变量，P=5.52×10）（趋势检验 P=2.71×10），而 EAC 的 WGS 与 GC 风险之间没有统计学上显著的相关性（作为连续变量，P=0.66）（趋势检验 P=0.70）。ESCC 而不是 EAC 可能与 GC 具有遗传易感性。10q23.33、5q11.2 和 12q24.12 上的遗传变异可能作为生物标志物，用于识别 ESCC 和 GC 风险均高的个体。
