title: Younger age of onset and multiple primary lesions associated with esophageal squamous cell carcinoma cases with a positive family history of the cancer suggests genetic predisposition.
abstract: BACKGROUND
  Previous epidemiological studies have consistently found a positive family history of esophageal cancer is associated with a significantly increased risk of the cancer. However, whether the elevated risk could be attributed to common household exposure or inherited susceptibility is uncertain. This study aimed to highlight the effect of genetic predisposition by noting the significant differences in onset age and multiple primary cancers between esophageal squamous cell carcinoma (ESCC) cases with or without a positive family history of the cancer.
  
  
  METHODS
  Age at onset and the percentage of multiple primary cancers were compared between ESCCs with (n = 766) or without (n = 1 776) a positive family history of the cancer in a consecutive surgery cohort at the Department of Thoracic Surgery of Hebei Tumor Hospital and the Fourth Hospital of Hebei Medical University.
  
  
  RESULTS
  Overall, ESCCs with a positive family history of the cancer featured both a significantly younger age of onset and significantly more multiple primary cancers than those with a negative family history (onset age 51.83 vs. 53.49 years old, P < 0.01; percent of multiple primary cancers 5.50% vs. 1.70%, χ(2) = 25.42, P < 0.01). Both the differences were evident in subgroup analyses, but did not correlate. While age at onset differed significantly by family history among the male, smoking, and drinking groups, the difference of multiple primary cancers was significant among the otherwise nonsmoking, nondrinking, and younger onset age groups.
  
  
  CONCLUSIONS
  Younger age of onset and multiple primary cancers associated with ESCCs with a positive, as opposed to a negative family history of the cancer, suggest a genetic predisposition. The results of subgroup analyses indicate a younger age of ESCC development results from the interaction of environmental and genetic risk factors, but multiple primary cancers may be related only to genetic predisposition.
authors.affiliation: Department of Surgery, Hebei Tumor Hospital and the Fourth Hospital of Hebei Medical University, Shijiazhuang, Hebei 050011, China.
authors.forename: Nan
authors.initials: N
authors.lastname: Jia
authors.affiliation: Department of Tumor Image, Hebei Tumor Hospital and the Fourth Hospital of Hebei Medical University, Shijiazhuang, Hebei 050011, China.
authors.forename: Xiaoduo
authors.initials: X
authors.lastname: Wen
authors.affiliation: Department of Medical Information, Hebei Tumor Hospital and the Fourth Hospital of Hebei Medical University, Shijiazhuang, Hebei 050011, China.
authors.forename: Nan
authors.initials: N
authors.lastname: Zhang
authors.affiliation: Department of Tumor Image, Hebei Tumor Hospital and the Fourth Hospital of Hebei Medical University, Shijiazhuang, Hebei 050011, China.
authors.forename: Yi
authors.initials: Y
authors.lastname: Yang
authors.affiliation: Department of Tumor Image, Hebei Tumor Hospital and the Fourth Hospital of Hebei Medical University, Shijiazhuang, Hebei 050011, China.
authors.forename: Liwei
authors.initials: L
authors.lastname: Zhang
authors.affiliation: Department of Pathology, Hebei Tumor Hospital and the Fourth Hospital of Hebei Medical University, Shijiazhuang, Hebei 050011, China.
authors.forename: Xiaoling
authors.initials: X
authors.lastname: Wang
authors.affiliation: Department of Oncology, Hebei Tumor Hospital and the Fourth Hospital of Hebei Medical University, Shijiazhuang, Hebei 050011, China.
authors.forename: Na
authors.initials: N
authors.lastname: Wang
authors.affiliation: Department of Oncology, Hebei Tumor Hospital and the Fourth Hospital of Hebei Medical University, Shijiazhuang, Hebei 050011, China. Email: dengguiwen@aliyun.com.
authors.forename: Denggui
authors.initials: D
authors.lastname: Wen
mesh_terms: D017668:Age of Onset; D002294:Carcinoma, Squamous Cell / Q000235:genetics*; D004938:Esophageal Neoplasms / Q000235:genetics*; D000077277:Esophageal Squamous Cell Carcinoma; D005260:Female; D020022:Genetic Predisposition to Disease / Q000235:genetics; D006801:Humans; D008297:Male; D008875:Middle Aged; D013274:Stomach Neoplasms / Q000235:genetics