title: Effects of NFKB1 and NFKBIA gene polymorphisms on susceptibility to environmental factors and the clinicopathologic development of oral cancer.
abstract: BACKGROUND
  Oral cancer, which is the fourth most common cancer in Taiwanese men, is associated with environmental carcinogens. The possibility that genetic predisposition in nuclear factor-kappa B (NF-κB)-signaling pathways activation is linked to the development of oral squamous cell carcinoma (OSCC) requires investigation. The current study examines associations between polymorphisms within promoter regions of NFKB1 encoding NF-κB1 and NFKBIA encoding IkappaBalpha (IκBα) with both the susceptibility to develop OSCC and the clinicopathological characteristics of the tumors.
  
  
  RESULTS
  Genetic polymorphisms of NFKB1 and NFKBIA were analyzed by a real-time polymerase chain reaction (real-time PCR) for 462 patients with oral cancer and 520 non-cancer controls. We found that NFKB1 -94 ATGG1/ATGG2, -94 ATGG2/ATGG2, and the combination of -94 ATGG1/ATGG2 and ATGG2/ATGG2 genotypes NFKBIA -826 T (CT+TT) and -881 G (AG+GG) allelic carriages, were more prevalent in OSCC patients than in non-cancer participants. Moreover, we found that NFKB1 or NFKBIA gene polymorphisms seem to be related to susceptibility to develop oral cancer linked to betel nut and tobacco consumption. Finally, patients with oral cancer who had at least one -519 T allele of the NFKBIA gene were at higher risk for developing distant metastasis (P<.05), compared with those patients CC homozygotes.
  
  
  CONCLUSIONS
  Our results suggest that NFKB1 -94 ATTG2, NFKBIA -826 T, and -881 G alleles are associated with oral carcinogenesis. The combination of NFKB1 or NFKBIA gene polymorphisms and environmental carcinogens appears related to an increased risk of oral cancer. More importantly, the genetic polymorphism of NFKBIA -519 might be a predictive factor for the distal metastasis of OSCC in Taiwanese.
authors.affiliation: Institute of Biochemistry and Biotechnology, Chung Shan Medical University, Taichung, Taiwan.
authors.forename: Chiao-Wen
authors.initials: CW
authors.lastname: Lin
authors.forename: Yih-Shou
authors.initials: YS
authors.lastname: Hsieh
authors.forename: Chung-Han
authors.initials: CH
authors.lastname: Hsin
authors.forename: Chun-Wen
authors.initials: CW
authors.lastname: Su
authors.forename: Chien-Huang
authors.initials: CH
authors.lastname: Lin
authors.forename: Lin-Hung
authors.initials: LH
authors.lastname: Wei
authors.forename: Shun-Fa
authors.initials: SF
authors.lastname: Yang
authors.forename: Ming-Hsien
authors.initials: MH
authors.lastname: Chien
mesh_terms: D000328:Adult; D000368:Aged; D000428:Alcohol Drinking / Q000009:adverse effects; D001114:Areca / Q000009:adverse effects; D044466:Asian People; D002294:Carcinoma, Squamous Cell / Q000235:genetics* / Q000473:pathology; D004198:Disease Susceptibility; D005260:Female; D056726:Genetic Association Studies; D006801:Humans; D020672:I-kappa B Proteins / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D009062:Mouth Neoplasms / Q000235:genetics* / Q000473:pathology*; D000072000:NF-KappaB Inhibitor alpha; D052002:NF-kappa B p50 Subunit / Q000235:genetics*; D011110:Polymorphism, Genetic; D011401:Promoter Regions, Genetic; D012907:Smoking / Q000009:adverse effects; D013624:Taiwan
chemical_list: D020672:I-kappa B Proteins; D052002:NF-kappa B p50 Subunit; C489548:NFKB1 protein, human; C000606204:NFKBIA protein, human; D000072000:NF-KappaB Inhibitor alpha