Genetic polymorphism of cytochrome P4501A1 and susceptibility to oral squamous cell carcinoma and oral precancer lesions associated with smoking/betel use.
BACKGROUND
The importance of the CYP1A1 polymorphisms at exon 7 (Ile/Val) and 3'-untranslated region (3'-UTR) has been controversial in oral squamous cell carcinoma (OSCC) or head and neck SCC (HNSCC) denoting the value of exploring the correlation between these polymorphisms and risk of betel/smoking associated OSCC. It is also important to evaluate the association between CYP1A1 polymorphisms and susceptibility of oral precancerous lesion (OPL) to confirm the findings in OSCC cases.


METHODS
We examined polymorphic prevalence of CYP1A1 at exon 7 (Ile/Val) and 3'-UTR in 106 cases with OSCC, 60 cases with OPL, and 146 controls. DNA isolated from surgical specimens and whole blood was used for PCR-based genotyping.


RESULTS
The prevalence of the CYP1A1 A/G genotype (Ile/Val) and G/G genotype (Val/Val) in exon 7 of cases with OSCC (79.2 and 7.6%) and OPL (68.3 and 10%) were significantly higher than in controls (53.4 and 1.4%) (P < 0.0001). The novelty of the present study is that we identified the onset age of OSCC in CYP1A1 A/G genotype to be significantly younger than that in A/A genotype (P < 0.01). No significant difference was seen between cases and controls regarding the polymorphisms at 3'-UTR.


CONCLUSIONS
The findings indicate that the individuals with the CYP1A1 exon 7 containing G allele were at increased risk for OSCC and OPL.
Kao
Shou-Yen
SY
Department of Dentistry, Oral and Maxillofacial Surgery, Taipei Veterans General Hospital, Taiwan, ROC. sykao@vghtpe.gov.tw
Wu
Cheng-Hsien
CH
Lin
Shu-Chun
SC
Yap
Soon-Kiong
SK
Chang
Che-Shoa
CS
Wong
Yong-Kie
YK
Chi
Lin-Yang
LY
Liu
Tsung-Yun
TY
D000293:Adolescent; D000328:Adult; D017668:Age of Onset; D000368:Aged; D000369:Aged, 80 and over; D019943:Amino Acid Substitution; D001114:Areca / Q000009:adverse effects; D002294:Carcinoma, Squamous Cell / Q000201:enzymology / Q000209:etiology / Q000235:genetics*; D019363:Cytochrome P-450 CYP1A1 / Q000235:genetics*; D005091:Exons / Q000235:genetics; D005260:Female; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D006801:Humans; D008297:Male; D008875:Middle Aged; D009062:Mouth Neoplasms / Q000201:enzymology / Q000209:etiology / Q000235:genetics*; D020125:Mutation, Missense; D012150:Polymorphism, Restriction Fragment Length; D011230:Precancerous Conditions / Q000201:enzymology / Q000209:etiology / Q000235:genetics*; D012907:Smoking / Q000009:adverse effects / Q000235:genetics; D020506:Untranslated Regions / Q000235:genetics; D014633:Valine / Q000235:genetics
D020506:Untranslated Regions; D019363:Cytochrome P-450 CYP1A1; D014633:Valine