Functional polymorphism in NFKB1 promoter is related to the risks of oral squamous cell carcinoma occurring on older male areca (betel) chewers.
Areca (betel)-chewing is tightly associated with the high prevalence of oral squamous cell carcinoma (OSCC) in Asians. NFKB1 encodes a 105kDa protein that can be processed to produce p50 subunit of nuclear factor-kappaB protein complex. A insertion (ins)/deletion (del) polymorphism (-94ins/delATTG) in NFKB1 promoter, which may drive the ins allele two-fold increase in NFKB1 transcription relative to del allele, was recently found. This study identified that the odds ratio in OSCC carrying ins allelotype were 1.78 relative to controls (56.7 vs 41.8%) in subjects more than 50 years old. L allelotype of Heme oxygenase-1 (HO-1), accounting for a long (GT)(n) repeat in HO-1 promoter, is associated with the risks of areca-related OSCC. Subjects carried both NFKB1 ins and HO-1 L allelotypes had significant risks for various subsets of OSCC. OSCC with lymph node metastasis or advanced stage had significantly higher frequency of NFKB1 ins and HO-1 L allelotypes. This study suggested that the functional NFKB1promoter polymorphism could be valuable for assessment of cancer risk.
Lin
Shu-Chun
SC
School of Dentistry, National Yang-Ming University, Li-Nong St, Sec. 2, Taipei 112, Taiwan, ROC.
Liu
Chung-Ji
CJ
Yeh
Wen-I
WI
Lui
Man-Tin
MT
Chang
Kuo-Wei
KW
Chang
Che-Shoa
CS
D000328:Adult; D000483:Alleles; D001114:Areca / Q000009:adverse effects*; D002294:Carcinoma, Squamous Cell / Q000209:etiology* / Q000235:genetics / Q000473:pathology; D018900:Dinucleotide Repeats / Q000235:genetics; D005787:Gene Frequency; D005838:Genotype; D051547:Heme Oxygenase-1 / Q000235:genetics; D006801:Humans; D008207:Lymphatic Metastasis; D008297:Male; D008875:Middle Aged; D009062:Mouth Neoplasms / Q000209:etiology* / Q000235:genetics / Q000473:pathology; D016254:Mutagenesis, Insertional / Q000235:genetics; D052002:NF-kappa B p50 Subunit / Q000235:genetics*; D009367:Neoplasm Staging; D016017:Odds Ratio; D011110:Polymorphism, Genetic / Q000235:genetics*; D011401:Promoter Regions, Genetic / Q000235:genetics*; D012307:Risk Factors; D017384:Sequence Deletion / Q000235:genetics
D052002:NF-kappa B p50 Subunit; C489548:NFKB1 protein, human; C496541:HMOX1 protein, human; D051547:Heme Oxygenase-1