Abstract
Chromosome 13q22.1 has previously been identified to be a susceptibility locus for pancreatic cancer in Chinese and European ancestry populations. This pleiotropy study aimed to identify novel variants in this region associated with susceptibility to different types of human cancer. To fine-map the 13q22.1 region, imputation analyses were conducted on the basis of the GWAS data of 2,031 esophageal squamous cell cancer (ESCC) cases and 2,044 controls and 5,930 SNPs (625 directly genotyped and 5,305 well imputed). Promising associations were then examined in ESCC (4,146 cases and 4,135 controls), gastric cardia cancer (1,894 cases and 1,912 controls), noncardia gastric cancer (1,007 cases and 2,243 controls), and colorectal cancer (1,111 cases and 1,138 controls). Fine mapping and biochemical analyses were further performed to elucidate the potential function of novel variants. Two novel variants, rs1924966 and rs115797771, were associated with ESCC risk (P = 1.37 × 10(-10) and P = 2.32 × 10(-10), respectively) and were also associated with risk of gastric cardia cancer (P = 0.0003 and P = 0.0018, respectively) but not gastric cancer and colorectal cancer. Fine-mapping revealed another SNP, rs58090485, in strong linkage disequili...Continue Reading
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