Gene-environment interaction involved in oral carcinogenesis: molecular epidemiological study for metabolic and DNA repair gene polymorphisms.
BACKGROUND
Exposure to environmental carcinogens leads to oral squamous cell carcinoma (OSCC); however, the impact of genetic variations in carcinogen metabolisms and DNA repair on OSCC risk considering environmental exposures has not been clearly elucidated.


METHODS
We conducted a case-control study with 122 cases and 241 controls. The risk of OSCC was evaluated in 10 genetic polymorphisms of nine genes, such as CYP1A1, CYP2E1, GSTM1, GSTT1, XPA, XPC, XPC, XPF and ERCC1. Gene-environment interaction was also evaluated.


RESULTS
We found that CYP2E1 and XPA polymorphisms significantly affected the OSCC risk. Gene-environment interactions with smoking were significant for CYP2E1 and ERCC1 polymorphisms. Odds ratios for gene-environment interaction were 7.98 (P = 0.036), 9.67 (P = 0.017) and 8.49 (P = 0.031) for CYP2E1RsaI, DraI and ERCC1 polymorphisms, respectively. No interaction was observed with heavy drinking and any polymorphisms.


CONCLUSIONS
CYP2E1, XPA and ERCC1 polymorphisms may affect the risk of OSCC.
Sugimura
Tomotaka
T
Central Laboratory and Radiation Biology, Aichi Cancer Center Research Institute, Nagoya, Japan. sugitomo@aichi-cc.jp
Kumimoto
Hiroshi
H
Tohnai
Iwai
I
Fukui
Takafumi
T
Matsuo
Keitaro
K
Tsurusako
Shinichi
S
Mitsudo
Kenji
K
Ueda
Minoru
M
Tajima
Kazuo
K
Ishizaki
Kanji
K
D000428:Alcohol Drinking / Q000009:adverse effects; D002294:Carcinoma, Squamous Cell / Q000209:etiology / Q000235:genetics*; D016022:Case-Control Studies; D019363:Cytochrome P-450 CYP1A1 / Q000235:genetics; D019392:Cytochrome P-450 CYP2E1 / Q000235:genetics; D004260:DNA Repair / Q000235:genetics*; D004268:DNA-Binding Proteins / Q000235:genetics; D004720:Endonucleases / Q000235:genetics; D004781:Environmental Exposure; D016021:Epidemiologic Studies; D005260:Female; D005982:Glutathione Transferase / Q000235:genetics; D006801:Humans; D008297:Male; D008875:Middle Aged; D017720:Molecular Epidemiology; D009062:Mouth Neoplasms / Q000209:etiology / Q000235:genetics*; D011110:Polymorphism, Genetic / Q000235:genetics*; D012307:Risk Factors; D012907:Smoking / Q000009:adverse effects; D011503:Transglutaminases / Q000235:genetics; D051760:Xeroderma Pigmentosum Group A Protein / Q000235:genetics
D019363:Cytochrome P-450 CYP1A1; D019392:Cytochrome P-450 CYP2E1; D004268:DNA-Binding Proteins; D004720:Endonucleases; D005982:Glutathione Transferase; D011503:Transglutaminases; D051760:Xeroderma Pigmentosum Group A Protein; C497314:XPA protein, human; C095888:xeroderma pigmentosum group F protein; C086984:XPC protein, human; C413545:glutathione S-transferase T1; C071447:ERCC1 protein, human