title: A high IL-4 production diplotype is associated with an increased risk but better prognosis of oral and pharyngeal carcinomas.
abstract: OBJECTIVE
  Interleukin (IL)-4 is a key cytokine in humoral and adaptive immunity. This study aimed to evaluate the association of IL-4 genetic variants (-590C>T and VNTR in intron 3) with the risk and prognosis of oral and pharyngeal squamous cell carcinoma (OPSCC).
  
  
  METHODS
  A total of 1215 subjects, which included 623 healthy controls and 592 OPSCC cases (463 oral squamous cell carcinoma (OSCC) and 129 pharyngeal squamous cell carcinoma (PSCC) cases), were recruited. The genotypes were determined by TaqMan real-time assay and PCR-based assay.
  
  
  RESULTS
  The IL-4 genotypes at locus -590C>T and intron 3 VNTR were not correlated with increased risk of OSCC, PSCC, and OPSCC, with the exception of early-stage OPSCC (at -590C>T: T/T vs. C/C+C/T, adjusted odds ratio (AOR)=1.42, 95% CI: 1.02-1.98; at intron 3 VNTR: RP1/RP1 vs. RP2/RP2+RP2/RP1, AOR=1.46, 95% CI: 1.05-2.04). Compared with other IL-4 diplotypes, the T,RP1/T,RP1 diplotype was associated with an increased risk of OPSCC (AOR=1.37, 95% CI: 1.03-1.81), particularly early-stage OSCC (AOR=1.43, 95% CI: 1.02-2.00), PSCC (AOR=2.35, 95% CI: 1.06-5.19), and OPSCC (AOR=1.52, 95% CI: 1.10-2.11). Interactions between the IL-4 diplotype and the alcohol drinking status were found to contribute to the risk of early-stage OPSCC (p=0.024). In addition, the T,RP1/T,RP1 diplotype was correlated with better disease-specific survival (T,RP1/T,RP1 vs. other diplotypes, adjusted hazard ratio=0.70, 95% CI: 0.50-0.97).
  
  
  CONCLUSIONS
  The T, RP1/T, RP1 diplotype of IL-4 was associated with an increased risk but favourable prognosis of OPSCC.
authors.affiliation: Department of Dentistry, Kaohsiung Veterans General Hospital, Kaohsiung, Taiwan; Department of Dental Laboratory Technology, Shu Zen College of Medicine & Management, Kaohsiung, Taiwan.
authors.forename: Cheng-Mei
authors.initials: CM
authors.lastname: Yang
authors.forename: Hung-Chih
authors.initials: HC
authors.lastname: Chen
authors.forename: Yu-Yi
authors.initials: YY
authors.lastname: Hou
authors.forename: Ming-Chien
authors.initials: MC
authors.lastname: Lee
authors.forename: Huei-Han
authors.initials: HH
authors.lastname: Liou
authors.forename: Sin-Jhih
authors.initials: SJ
authors.lastname: Huang
authors.forename: Liang-Ming
authors.initials: LM
authors.lastname: Yen
authors.forename: Dong-Mei
authors.initials: DM
authors.lastname: Eng
authors.forename: Yao-Dung
authors.initials: YD
authors.lastname: Hsieh
authors.forename: Luo-Ping
authors.initials: LP
authors.lastname: Ger
mesh_terms: D000328:Adult; D000428:Alcohol Drinking / Q000009:adverse effects; D001114:Areca / Q000009:adverse effects; D002294:Carcinoma, Squamous Cell / Q000235:genetics*; D016022:Case-Control Studies; D005260:Female; D005838:Genotype; D006801:Humans; D015847:Interleukin-4 / Q000235:genetics*; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D009062:Mouth Neoplasms / Q000235:genetics*; D009364:Neoplasm Recurrence, Local / Q000235:genetics*; D016017:Odds Ratio; D010610:Pharyngeal Neoplasms / Q000235:genetics*; D016133:Polymerase Chain Reaction; D011110:Polymorphism, Genetic; D011379:Prognosis; D016016:Proportional Hazards Models; D012306:Risk; D012907:Smoking / Q000009:adverse effects
chemical_list: D015847:Interleukin-4
keywords: Interleukin-4; Oral cancer; Pharyngeal cancer; Polymorphisms; Prognostic factor; Risk factor