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 × 10−8), rs10052657 in PDE4D at 5q11.2 (per C allele: OR = 1.12, 95% CI: 1.01–1.25, P = 3.28 × 10−2) and rs671 in ALDH2 at 12q24.12 (per A-allele: OR = 0.83, 95% CI: 0.75–0.91, P = 1.14 × 10−4) 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 × 10−8). High WGS of ESCC was also associated with increased risk of GC (P = 5.52 × 10−4 as a continuous variable) (trend test P = 2.71 × 10−4), 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.
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We thank all the participants of the Nanjing/Beijing and the National Cancer Institute gastric cancer studies. This study was supported by grants from the National key research and development program of China (grant no. 2016YFC1302703); and National Natural Science Foundation of China (81521004, 81422042, 81872702).
Conflict of interest
The authors declare that they have no conflict of interest.
Human rights statement and informed consent
All procedures followed were in accordance with the ethical standards of the responsible committee on human experimentation (institutional and national) and with the Helsinki Declaration of 1964 and later versions. Informed consent to be included in the study, or the equivalent, was obtained from all patients.
Authors share co-first authorship: Linhua Yao, Fei Yu, Yingying Mao
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Yao, L., Yu, F., Mao, Y. et al. Gastric cancer may share genetic predisposition with esophageal squamous cell carcinoma in Chinese populations. J Hum Genet 63, 1159–1168 (2018). https://doi.org/10.1038/s10038-018-0501-4