title: Esophageal cancer in high-risk areas of China: research progress and challenges.
abstract: The extremely high incidence of esophageal cancer in certain rural areas of China has prompted significant intellectual curiosity and research efforts both in China and abroad.
  
  
  
  We summarize the research progress over the past several decades in high-risk areas (Linxian, Cixian, Shexian, and Yanting) based on literature research and our field trip (2012-2013).
  
  
  
  Considerable progress in clarifying the environmental risk factors and pathogenesis of esophageal cancer in high-risk areas has been achieved over the past several decades. Epidemiologic evidence suggests that carcinogen exposure and nutritional deficiency, rather than smoking and drinking, may be the major risk factors for esophageal cancer in the Taihang Mountains region, where the incidence of esophageal cancer is among the highest in the world. Two genome-wide association studies have identified variants in PLCE1 at 10q23 that are significantly associated with esophageal cancer risk. Recent whole-exome studies have revealed a comprehensive mutation pattern, in which the C>T transition is the predominant mutation type.
  
  
  
  Despite extensive research, the main causative factors that contribute to esophageal cancer in high-risk areas have not yet been elucidated. Challenges in this research area include determining the causative role of nitrosamine, identifying other potential carcinogens, and conducting fruitful international collaborative studies based on a multidisciplinary approach. Increased international collaboration will contribute to a better understanding of the etiology of esophageal cancer.
authors.affiliation: Department of Public Health, School of Medicine, Aichi Medical University, Nagakute, Japan.
authors.forename: Yingsong
authors.initials: Y
authors.lastname: Lin
authors.affiliation: Division of Carcinogenesis and Cancer Prevention, National Cancer Center Research Institute, Tokyo, Japan.
authors.forename: Yukari
authors.initials: Y
authors.lastname: Totsuka
authors.affiliation: Hebei Cancer Research Center, The Fourth Hospital of Hebei Medical University, Shijiazhuang, China.
authors.forename: Baoen
authors.initials: B
authors.lastname: Shan
authors.affiliation: Department of Public Health, School of Medicine, Aichi Medical University, Nagakute, Japan.
authors.forename: Chaochen
authors.initials: C
authors.lastname: Wang
authors.affiliation: Cancer Institute/Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China.
authors.forename: Wenqiang
authors.initials: W
authors.lastname: Wei
authors.affiliation: Cancer Institute/Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China.
authors.forename: Youlin
authors.initials: Y
authors.lastname: Qiao
authors.affiliation: Department of Public Health, School of Medicine, Aichi Medical University, Nagakute, Japan.
authors.forename: Shogo
authors.initials: S
authors.lastname: Kikuchi
authors.affiliation: AXA Department of Health and Human Security, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan.
authors.forename: Manami
authors.initials: M
authors.lastname: Inoue
authors.affiliation: Division of Epidemiology and Prevention, Aichi Cancer Center Research Institute, Nagoya, Japan.
authors.forename: Hideo
authors.initials: H
authors.lastname: Tanaka
authors.affiliation: Hebei Cancer Research Center, The Fourth Hospital of Hebei Medical University, Shijiazhuang, China. Electronic address: hytong69@yahoo.com.
authors.forename: Yutong
authors.initials: Y
authors.lastname: He
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D044466:Asian People / Q000706:statistics & numerical data; D002273:Carcinogens / Q000633:toxicity*; D002294:Carcinoma, Squamous Cell / Q000453:epidemiology* / Q000209:etiology* / Q000235:genetics; D002681:China / Q000453:epidemiology; D004938:Esophageal Neoplasms / Q000453:epidemiology* / Q000209:etiology* / Q000235:genetics; D005260:Female; D005544:Forecasting; D020022:Genetic Predisposition to Disease / Q000453:epidemiology; D006801:Humans; D015994:Incidence; D008297:Male; D008875:Middle Aged; D012307:Risk Factors; D012424:Rural Population / Q000706:statistics & numerical data* / Q000639:trends*
chemical_list: D002273:Carcinogens
keywords: Carcinogen exposure; China; Esophageal cancer; Etiology