title: Two novel variants on 13q22.1 are associated with risk of esophageal squamous cell carcinoma.
abstract: BACKGROUND
  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.
  
  
  METHODS
  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.
  
  
  RESULTS
  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 disequilibrium with rs115797771 (r(2) = 0.94). Functional analysis showed that this SNP disturbs a transcriptional repressor binding to the promoter region of KLF5, which might result in high constitutional expression of KLF5.
  
  
  CONCLUSIONS
  These results demonstrate that variants mapped on 13q22.1 are associated with the risk of different types of cancer.
  
  
  CONCLUSIONS
  13q22.1 might serve as a biomarker for the identification of individuals at risk for ESCC and gastric cardia cancer.
authors: Department of Etiology and Carcinogenesis, Cancer Institute and Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
authors: Jiang
authors: J
authors: Chang
authors: State Key Laboratory of Molecular Oncology, Cancer Institute and Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
authors: Lixuan
authors: L
authors: Wei
authors: Key Laboratory for Environment and Health (Ministry of Education), School of Public Health, Tongji Medical College, Huazhong University of Sciences and Technology, Wuhan, China.
authors: Xiaoping
authors: X
authors: Miao
authors: State Key Laboratory of Molecular Oncology, Cancer Institute and Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
authors: Dianke
authors: D
authors: Yu
authors: Department of Etiology and Carcinogenesis, Cancer Institute and Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China. State Key Laboratory of Molecular Oncology, Cancer Institute and Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
authors: Wen
authors: W
authors: Tan
authors: Department of Molecular Genetics, College of Life Science, Hebei United University, Tangshan, China. chenwu@cicams.ac.cn jyxuemei@gmail.com.
authors: Xuemei
authors: X
authors: Zhang
authors: Department of Etiology and Carcinogenesis, Cancer Institute and Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China. chenwu@cicams.ac.cn jyxuemei@gmail.com.
authors: Chen
authors: C
authors: Wu
authors: State Key Laboratory of Molecular Oncology, Cancer Institute and Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
authors: Dongxin
authors: D
authors: Lin
mesh_terms: D002294:Carcinoma, Squamous Cell / Q000235:genetics*; D016022:Case-Control Studies; D002874:Chromosome Mapping; D002882:Chromosomes, Human, Pair 13 / Q000235:genetics*; D024202:Electrophoretic Mobility Shift Assay; D004938:Esophageal Neoplasms / Q000235:genetics*; D005260:Female; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D006801:Humans; D051741:Kruppel-Like Transcription Factors / Q000235:genetics; D015810:Linkage Disequilibrium / Q000235:genetics; D008297:Male; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D012307:Risk Factors
chemical_list: C492214:KLF5 protein, human; D051741:Kruppel-Like Transcription Factors