Metabolic polymorphisms, smoking, and oral cancer in Puerto Rico.
Genetic polymorphisms resulting in variation in metabolism of tobacco carcinogens may influence oral cancer risk. In a population-based case-control study in Puerto Rico, genotypes of CYP1A1, GSTM1, and GSTT1 were determined by a PCR-based method for 132 oral cancer patients and 143 control subjects. Genotype-associated risks were estimated by logistic regression. The null variant of GSTM1 was associated with a marginally significant decrease in oral cancer risk [odds ratio (OR) = 0.6, 95% confidence interval (CI) = 0.3-1.0, and P for trend = 0.09]. Risks increased with increasing cigarette use among subjects with the GSTM1-present genotype (P for trend <0.0001), rising to OR = 9.5, 95% CI = 3.0-30, among the heaviest cigarette users. In contrast, among subjects with the GSTM1-null genotype, risks did not clearly increase with increasing cigarette use (P for trend <0.61; OR = 1.8, 95% CI = 0.6-5.2 among the heaviest tobacco users). The GSTT1-null variant (OR = 1.0, 95% CI = 0.5-1.9) and CYP1A1(462Val) variant (OR = 0.9, 95% CI = 0.5-1.7) were not associated with the risk. Risks rose with increasing cigarette use in a similar manner for subjects with or without the CYP1A1(462Val) variant (P for interaction = 0.3) and for subjects with or without the GSTT1-null genotype (P for interaction = 0.4). In conclusion, cigarette use significantly increased the risk of oral cancer in this population. The GSTM1-present genotype was associated with higher tobacco-associated risk for oral cancer among heavy smokers than the null genotype.
Xie
Heng
H
Division of Cancer Treatment and Diagnosis, National Cancer Institute, Bethesda, MD 20892, USA.
Hou
Lifang
L
Shields
Peter G
PG
Winn
Deborah M
DM
Gridley
Gloria
G
Bravo-Otero
Eleuterio
E
Diehl
Scott R
SR
Bowman
Elise D
ED
Brown
Linda M
LM
Hayes
Richard B
RB
D000368:Aged; D000428:Alcohol Drinking; D019363:Cytochrome P-450 CYP1A1 / Q000235:genetics; D004032:Diet; D005260:Female; D005638:Fruit; D005838:Genotype; D005982:Glutathione Transferase / Q000235:genetics; D006801:Humans; D008297:Male; D009062:Mouth Neoplasms / Q000453:epidemiology / Q000235:genetics*; D011110:Polymorphism, Genetic / Q000235:genetics*; D011647:Puerto Rico / Q000453:epidemiology; D012307:Risk Factors; D012907:Smoking / Q000235:genetics*; D014675:Vegetables
D019363:Cytochrome P-450 CYP1A1; D005982:Glutathione Transferase; C413545:glutathione S-transferase T1