title: Interaction between tumour necrosis factor-α gene polymorphisms and substance use on risk of betel quid-related oral and pharyngeal squamous cell carcinoma in Taiwan.
abstract: OBJECTIVE
  Betel quid (BQ) components induce the secretion of tumour necrosis factor-alpha (TNF-α) in oral keratinocytes, which promotes oral mucosal inflammation and oral cancer. This study was carried out to evaluate the association of TNFA genetic variants (-308G>A and -238G>A) with the risk and prognosis of BQ-related oral and pharyngeal squamous cell carcinoma (OPSCC).
  
  
  METHODS
  A total of 403 subjects (205 cancer cases and 198 healthy controls) who habitually chewed BQ were recruited. The genotypes were determined by TaqMan real-time assays.
  
  
  RESULTS
  G allele and G/G genotype at TNFA -308 were associated with a 1.95-fold (95%CI: 1.16-3.28, p(corrected)=0.024) and 2.28-fold (95%CI: 1.30-4.00, p(corrected)=0.008) increased risk of cancer as compared to those with A allele or A/A+A/G genotypes, respectively. In addition, G allele (p=0.080) and G/G genotype (p=0.076) at TNFA -238 were associated with a borderline but statistically significant increased risk of OPSCC. The combined G/G+G/G genotype at both loci had a 2.37-fold increased risk of OPSCC as compared to those with other combined genotypes (95%CI: 1.41-4.00, p=0.001). Interactions between combined genotypes and smoking status were also found to contribute to risk of BQ-related OPSCC. There was no association of TNFA genotypes with clinicopathologic findings or the survival of OPSCC patients.
  
  
  CONCLUSIONS
  BQ-chewers who carry the G allele or G/G genotype in TNFA -308 may have an increased risk of OPSCC. The intensity of cigarette smoking modulates the effect of the combined TNFA genotypes on risk of BQ-related OPSCC.
authors.affiliation: Department of Dentistry, Kaohsiung Veterans General Hospital, Kaohsiung, Taiwan.
authors.forename: Cheng-Mei
authors.initials: CM
authors.lastname: Yang
authors.forename: Yu-Yi
authors.initials: YY
authors.lastname: Hou
authors.forename: Yi-Ten
authors.initials: YT
authors.lastname: Chiu
authors.forename: Hung-Chih
authors.initials: HC
authors.lastname: Chen
authors.forename: Sau-Tung
authors.initials: ST
authors.lastname: Chu
authors.forename: Chao-Chuan
authors.initials: CC
authors.lastname: Chi
authors.forename: Michael
authors.initials: M
authors.lastname: Hsiao
authors.forename: Chien-Yiing
authors.initials: CY
authors.lastname: Lee
authors.forename: Christina Jen-Chia
authors.initials: CJ
authors.lastname: Hsieh
authors.forename: Yu-Chen
authors.initials: YC
authors.lastname: Lin
authors.forename: Yao-Dung
authors.initials: YD
authors.lastname: Hsieh
authors.forename: Luo-Ping
authors.initials: LP
authors.lastname: Ger
mesh_terms: D000225:Adenine; D000328:Adult; D000368:Aged; D000428:Alcohol Drinking / Q000009:adverse effects; D000483:Alleles; D001114:Areca / Q000009:adverse effects*; D002294:Carcinoma, Squamous Cell / Q000209:etiology* / Q000235:genetics / Q000556:secondary; D016022:Case-Control Studies; D002874:Chromosome Mapping; D005006:Ethnicity; D020022:Genetic Predisposition to Disease / Q000235:genetics; D014644:Genetic Variation / Q000235:genetics; D005838:Genotype; D006147:Guanine; D006801:Humans; D008297:Male; D008875:Middle Aged; D009062:Mouth Neoplasms / Q000209:etiology* / Q000235:genetics / Q000473:pathology; D009364:Neoplasm Recurrence, Local / Q000473:pathology; D009367:Neoplasm Staging; D010610:Pharyngeal Neoplasms / Q000209:etiology* / Q000235:genetics / Q000473:pathology; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D011379:Prognosis; D012307:Risk Factors; D012907:Smoking / Q000009:adverse effects; D015996:Survival Rate; D013624:Taiwan; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics*
chemical_list: D014409:Tumor Necrosis Factor-alpha; D006147:Guanine; D000225:Adenine