title: HPV seropositivity joints with susceptibility loci identified in GWASs at apoptosis associated genes to increase the risk of Esophageal Squamous Cell Carcinoma (ESCC).
abstract: BACKGROUND
  We previously showed that human papillomavirus (HPV) serostatus was not an independent risk factor for esophageal squamous cell carcinoma(ESCC) in nonsmokers and nondrinkers; however, HPV increased the risk in smokers.
  
  
  METHODS
  Here we investigated possible interactions between HPV16 serostatus and three susceptibility loci identified in GWASs at apoptosis associated genes with regard to risk of ESCC in a case-control study of 313 patients with ESCC and 314 healthy controls. The loci (CHK2 rs738722, C12orf51 rs2074356, and PLCE1 rs2274223) were genotyped, and the presence or absence of HPV16 in serum was measured by ELISA. Multivariable logistic regression was used to evaluate possible interactions of HPV16 serostatus and the three loci on the risk of ESCC.
  
  
  RESULTS
  A significant interaction was found between HPV16 serology and rs2074356 (P = 0.005, odds ratio [OR] 1.40, 95% confidence interval [CI] 1.11-1.77) or rs2274223 (P < 0.001, OR 1.53, 95% CI 1.23-1.91), but not for rs738722. For rs2074356, risk of ESCC was increased substantially in smokers (P < 0.001, OR 8.25, 95% CI 3.84-17.71) and drinkers (OR4.04, P = 0.001, 95% CI 1.79-9.10) who carried risk alleles (TT or TC genotype) and were HPV16-seropositive. Similar results were observed for rs2274223 in smokers (P < 0.001, OR6.06, 95% CI 2.85-12.88) and drinkers (P < 0.001, OR 5.43, 95% CI 2.51-11.76), but not for rs738722.
  
  
  CONCLUSIONS
  Consistent with the previous study, loci at rs2074356 and rs2274223 could increase the risk of ESCC, furthermore, there were significant interactions between HPV sero-status and the susceptibility loci on the risk of ESCC. This effect could be modified obviously by smoking and drinking.
authors.forename: Ju
authors.initials: J
authors.lastname: Yang
authors.forename: Huanlei
authors.initials: H
authors.lastname: Wu
authors.forename: Sheng
authors.initials: S
authors.lastname: Wei
authors.forename: Huihua
authors.initials: H
authors.lastname: Xiong
authors.forename: Xiangning
authors.initials: X
authors.lastname: Fu
authors.forename: Zhaozhen
authors.initials: Z
authors.lastname: Qi
authors.forename: Qian
authors.initials: Q
authors.lastname: Jiang
authors.forename: Wen
authors.initials: W
authors.lastname: Li
authors.forename: Guangyuan
authors.initials: G
authors.lastname: Hu
authors.affiliation: Departments of Oncology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China. yxl@medmail.com.cn.
authors.forename: Xianglin
authors.initials: X
authors.lastname: Yuan
authors.forename: Zhongxing
authors.initials: Z
authors.lastname: Liao
mesh_terms: D000368:Aged; D000428:Alcohol Drinking / Q000235:genetics; D017209:Apoptosis; D002294:Carcinoma, Squamous Cell / Q000097:blood / Q000175:diagnosis / Q000235:genetics* / Q000821:virology*; D004938:Esophageal Neoplasms / Q000097:blood / Q000175:diagnosis / Q000235:genetics* / Q000821:virology*; D000077277:Esophageal Squamous Cell Carcinoma; D005260:Female; D056426:Genetic Loci; D020022:Genetic Predisposition to Disease; D055106:Genome-Wide Association Study; D052162:Human papillomavirus 16 / Q000276:immunology*; D006801:Humans; D008297:Male; D008875:Middle Aged; D030361:Papillomavirus Infections / Q000276:immunology / Q000821:virology; D054801:Phosphoinositide Phospholipase C / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D012907:Smoking / Q000235:genetics; D044767:Ubiquitin-Protein Ligases / Q000235:genetics*
chemical_list: D044767:Ubiquitin-Protein Ligases; D054801:Phosphoinositide Phospholipase C; C423320:phospholipase C epsilon