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Metabolic Polymoryphisms, Smoking, and Oral Cancer in Puerto Rico

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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 CYP1A1462Val 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 CYP1A1462Val 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.
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Keywords: Carcinoma; Enzymes; Polymorphism; Smoking

Document Type: Research Article

Affiliations: 1: *Division of Cancer Treatment and Diagnosis, National Cancer Institute, Bethesda, MD 20892 2: †Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, MD 20892 3: ¶Lombardi Cancer Center, Georgetown University Medical Center, Washington, DC 20007 4: ‡Division of Cancer Control and Population Sciences, National Cancer Institute, Bethesda, MD 20892 5: #School of Dentistry, University of Puerto Rico, San Juan, PR 00936-5067 6: **Center for Pharmacogenomics and Complex Disease Research, New Jersey Dental School, UMDNJ, Newark, NJ 07101-1709 7: §Laboratory of Human Carcinogenesis, National Cancer Institute, Bethesda, MD 20892

Publication date: 01 January 2003

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