We conducted a genome-wide association study of gastric cancer (GC) and esophageal squamous cell carcinoma (ESCC) in ethnic Chinese subjects in which we genotyped 551,152 single nucleotide polymorphisms (SNPs). We report a combined analysis of 2,240 GC cases, 2,115 ESCC cases, and 3,302 controls drawn from five studies. In logistic regression models adjusted for age, sex, and study, multiple variants at 10q23 had genome-wide significance for GC and ESCC independently. A notable signal was rs2274223, a nonsynonymous SNP located in PLCE1, for GC (P=8.40×1010Information Management Services Inc.Silver SpringMarylandUNITED STATES; per allele odds ratio (OR) = 1.31) and ESCC (P=3.85×10−9; OR = 1.34). The association with GC differed by anatomic subsite. For tumors located in the cardia the association was stronger (P=4.19 × 10−15; OR= 1.57) and for those located in the noncardia stomach it was absent (P=0.44; OR=1.05). Our findings at 10q23 could provide insight into the high incidence rates of both cancers in China.

NCT01688908; Pre-results.

We conducted a joint (pooled) analysis of three genome-wide association studies (GWAS) 1-3 of esophageal squamous cell carcinoma (ESCC) in ethnic Chinese (5,337 ESCC cases and 5,787 controls) with 9,654 ESCC cases and 10,058 controls for follow-up. In a logistic regression model adjusted for age, sex, study, and two eigenvectors, two new loci achieved genome-wide significance, marked by rs7447927 at 5q31.2 (per-allele odds ratio (OR) = 0.85, 95% CI 0.82-0.88; P=7.72x10−20) and rs1642764 at 17p13.1 (per-allele OR= 0.88, 95% CI 0.85-0.91; P=3.10x10−13). rs7447927 is a synonymous single nucleotide polymorphism (SNP) in TMEM173 and rs1642764 is an intronic SNP in ATP1B2, near TP53. Furthermore, a locus in the HLA class II region at 6p21.32 (rs35597309) achieved genome-wide significance in the two populations at highest risk for ESSC (OR=1.33, 95% CI 1.22-1.46; P=1.99x10−10). Our joint analysis identified new ESCC susceptibility loci overall as well as a new locus unique to the ESCC high risk Taihang Mountain region.

A consensus treatment strategy for esophageal squamous cell carcinoma (ESCC) patients who recur after definitive radiochemotherapy/radiotherapy has not been established. This study compared the outcomes in ESCC patients who underwent salvage surgery, salvage chemoradiation (CRT) or best supportive care (BSC) for local recurrence. Ninety-five patients with clinical stage I to III ESCC who had completely responded to the initial definitive radiochemotherapy or radiotherapy alone and developed local recurrence were enrolled in this study. Fifty-one of them received salvage esophagectomy, and R0 resection was performed in 41 patients, 36 underwent salvage CRT, and the remaining eight patients received BSC only. The 5-year overall survival was 4.6% for the 87 patients receiving salvage surgery or CRT, while all patients in the BSC group died within 12.0 months, the difference was statistically significant (P = 0.018). The 1-, 3-, 5-year survival rates in the salvage surgery and salvage CRT groups were 45.1%, 20.0%, 6.9% and 51.7%, 12.2%, 3.1%, respectively, there was no difference of overall survival between the two groups (P = 0.697). Patients also presented with lymph node relapse had inferior survival compared to those with isolated local tumor recurrence after salvage therapy. In the salvage surgery group, infections occurred in eight patients, and three developed anastomotic leakage. In the salvage CRT group, grade 2-4 esophagitis and radiation pneumonitis was observed in 19 and 3 patients, respectively. Seven patients (19.4%) developed esophagotracheal fistula or esophageal perforation. This study of salvage CRT versus salvage surgery for recurrent ESCC after definitive radiochemotherapy or radiotherapy alone did not demonstrate a statistically significant survival difference, but the frequency of complications including esophagotracheal fistula and esophageal perforation following salvage CRT was high.

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