Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology
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Cancer Epidemiol. Biomarkers Prev. · Sep 1996
Comparative StudyCytochrome P4501A2: enzyme induction and genetic control in determining 4-aminobiphenyl-hemoglobin adduct levels.
Cytochrome P4501A2 (CYP1A2) activity may be related to bladder cancer risk through metabolic activation of aromatic amines, such as 4-aminobiphenyl (ABP), to reactive intermediates that can form DNA and hemoglobin (Hb) adducts. In the context of a study on smoking and bladder cancer risk, 97 healthy male volunteers were investigated. CYP1A2-dependent N-oxidation activity was measured using a molar ratio of urinary caffeine metabolites [(paraxanthine + 1,7-dimethyluric acid)/caffeine] obtained between the fourth and fifth h after drinking a standardized cup of coffee. ⋯ Blond tobacco smokers exhibited higher adduct levels compared with black tobacco smokers, after adjustment for the quantity of cigarettes smoked. At the highest levels of smoking exposure, no major difference in ABP-Hb adduct levels was found among the different combinations of CYP1A2 and N-acetyltransferase-2 phenotypes. In a subset of only 45 available samples, no association was seen between the ABP-Hb adduct levels and the glutathione S-transferase M1 genotype.
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Cancer Epidemiol. Biomarkers Prev. · Jul 1996
Metabolites of a tobacco-specific nitrosamine, 4-(methylnitrosamino)- 1-(3-pyridyl)-1-butanone (NNK), in the urine of smokeless tobacco users: relationship between urinary biomarkers and oral leukoplakia.
Two metabolites of the carcinogenic tobacco-specific nitrosamine 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone were quantified in the urine of smokeless tobacco users. The metabolites are 4-(methylnitrosamino) -1-(3-pyridyl)-1-butanol (NNAL) and [4-(methylnitrosamino)-1-(3-pyridyl) but-1-yl]-beta-O-D-glucosiduronic acid (NNAL-Gluc). The study population consisted of 47 male nonsmokers, of whom 23 were snuff dippers, 13 were tobacco chewers, 3 were users of both products, and 8 were nonusers. ⋯ When the total levels of NNAL-Gluc, NNAL, or NNAL-Gluc + NNAL were divided into tertiles, there was a significant association between the presence of leukoplakia and increasing levels of these metabolites; a similar relationship was found between urinary cotinine and leukoplakia. The results of this study demonstrate that there is significant uptake of carcinogenic nitrosamines in smokeless tobacco users, and that such products are not harmless alternatives to cigarettes. Moreover, the urinary biomarkers NNAL-Gluc, NNAL, and cotinine were associated with the presence of leukoplakia, which provides biochemical support for the role of smokeless tobacco products as a cause of oral leukoplakia.
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Cancer Epidemiol. Biomarkers Prev. · May 1996
Randomized Controlled Trial Multicenter Study Comparative Study Clinical TrialThe polyp prevention trial I: rationale, design, recruitment, and baseline participant characteristics.
The Polyp Prevention Trial (PPT) is a multicenter randomized controlled trial examining the effect of a low-fat (20% of total energy intake), high-fiber (18 g/1000 kcal), high-vegetable and -fruit (5-8 daily servings) dietary pattern on the recurrence of adenomatous polyps of the large bowel, precursors of most colorectal malignancies. Eligibility criteria include one or more adenomas removed within 6 months of randomization; complete nonsurgical polyp removal and complete colonic examination to the cecum at the qualifying colonoscopy: age 35 years of more; no history of colorectal cancer, inflammatory bowel disease, or large bowel resection; and satisfactory completion of a food frequency questionnaire and 4-day food record. Of approximately 38,277 potential participants with one or more polyps recently resected, investigators at eight clinical centers randomized 2,079 (5.4%; 1,037 in the intervention and 1,042 in the control arm) between June 1991 and January 1994, making the PPT the largest adenoma recurrence trial ever conducted. ⋯ The trial provides 90% power to detect a reduction of 24% in the annual adenoma recurrence rate. The primary analytic period, on which sample size calculations were based is 3 years (T(1) to T(4)), which permits a 1-year lag time for the intervention to work and allows a more definitive clearing of lesions at T(1), given that at least 10-15% of polyps may be missed at baseline. The final (T(4)) colonoscopies are expected to be completed in early 1998.
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Cancer Epidemiol. Biomarkers Prev. · Dec 1995
Effects of watercress consumption on metabolism of a tobacco-specific lung carcinogen in smokers.
Epidemiological studies indicate that vegetable consumption protects against lung cancer in humans, but the protective constituents have not been identified. Phenethyl isothiocyanate (PEITC), which is release upon chewing of watercress (nasturtium officinale), is a chemopreventive agent against lung cancer induced by the tobacco-specific lung carcinogen 4- (methylnitrosamino)-1-(3-pyridyl-1-butanone (NNK) in rats and mice. PEITC inhibits the carcinogenicity of NNK by inhibiting its metabolic activation and thereby increasing the levels of detoxified metabolites excreted in urine. ⋯ The percentage of increase in urinary NNAL plus NNAL-Gluc during days 2 and 3 of the watercress consumption period correlated with intake of PEITC during this period, as measured by total urinary PEITC-NAC (r = 0.62; P = 0.04). The results of this study support our hypothesis that PEITC inhibits this oxidative metabolism of NNK in humans, as seen in rodents, and support further development of PEITC as a chemopreventive agent against lung cancer. This is the first study to report an effect of vegetable consumption on metabolism of a lung carcinogen in humans.
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Cancer Epidemiol. Biomarkers Prev. · Dec 1995
Glutathione S-transferase M1 genotype affects aminobiphenyl-hemoglobin adduct levels in white, black and Asian smokers and nonsmokers.
Cigarette smoking is the major cause of bladder cancer in men in the United States, and the arylamines contained in cigarettes smoke, including 4-amino-biphenyl (4-ABP), are believed to play an important role in the induction of bladder cancer among smokers. N-acetylation, which is catalyzed by the genetically controlled hepatic N-acetyltransferase enzyme displaying two phenotypes (slow versus rapid), is a detoxification pathway for arylamines with regard to bladder carcinogenesis. In Los Angeles, CA, non-Hispanic white (white), black, and Asian males have comparable smoking habits and yet dramatically different risks of bladder cancer (31 of 100,000 in whites, 16 of 100,000 in blacks, and 13 of 100,000 in Chinese and Japanese). ⋯ Mean level of 4-ABP hemoglobin adduct (adjusting for race, cigarette smoking, and acetylator phenotype) was significantly higher in subjects possessing the GSTM1-null versus GSTM1-non-null genotype (46.5 versus 36.0 pg/g Hb; P = 0.037). The comparable difference in mean levels of 3-ABP hemoglobin adduct was borderline significant (1.6 versus 1.1 pg/g Hb; P = 0.07). Thus, our results suggest that GSTM1 is involved in the detoxification of 3- and 4-ABP and may contribute to the racial variation in bladder cancer incidence among white, black, and Asian males in Los Angeles, CA.