Joint analysis of three genome-wide association studies of esophageal squamous cell carcinoma in Chinese populations

Dongxin Lin, Philip Taylor, Li-Dong Wang and colleagues have now pooled three genome-wide association analyses of esophageal squamous cell carcinoma, finding two new risk loci at genome-wide significance and an HLA class II locus of significance in high-risk populations. They reanalyze the strength of evidence for previously published risk loci. We conducted a joint (pooled) analysis of three genome-wide association studies (GWAS) 1 , 2 , 3 of esophageal squamous cell carcinoma (ESCC) in individuals of Chinese ancestry (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% confidence interval (CI) = 0.82–0.88; P = 7.72 × 10 −20 ) and rs1642764 at 17p13.1 (per-allele OR = 0.88, 95% CI = 0.85–0.91; P = 3.10 × 10 −13 ). rs7447927 is a synonymous 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 = 1.99 × 10 −10 ). Our joint analysis identifies new ESCC susceptibility loci overall as well as a new locus unique to the population in the Taihang Mountain region at high risk of ESCC.