Dataset Information

Heterocyclic amine intake, smoking, cytochrome P450 1A2 and N-acetylation phenotypes, and risk of colorectal adenoma in a multiethnic population.

ABSTRACT: Heterocyclic amines (HAA) are animal carcinogens that are present in meat cooked at high temperature and in tobacco smoke. These compounds require activation by cytochrome P450 1A2 (CYP1A2) and N-acetyltransferase-2 (NAT2) before they can damage DNA. This study tested the hypotheses that well-done meat and cigarette smoking increase the risk of adenoma, the precursor to most colorectal cancers, especially in individuals with rapid CYP1A2 and rapid NAT2 activities.An endoscopy-based case-control study of adenoma was conducted among Caucasians, Japanese and native Hawaiians to test this hypothesis. The overall diet and consumption of well-done meat cooked by various high-temperature methods were assessed by interview in 1016 patients with a first adenoma and 1355 controls with a normal endoscopy. A caffeine test was used to assess CYP1A2 and NAT2 activities in 635 cases and 845 controls. Logistic regression was used to account for matching factors and potential confounders.Smoking was associated with an increased risk of adenoma. Weak non-significant elevated OR were observed for the main effects of HAA intakes or NAT2 activity. However, the combined effects of HAA intakes and NAT2 activity were statistically significant. Subjects in both the upper tertiles of NAT2 activity and HAA intake were at increased risk of adenoma compared with subjects in the lower tertiles of NAT2 activity and exposure (2-amino-3,4,8-dimethylimidazo[4,5-f]quinoxaline intake OR 1.70, 95% CI I 1.06 to 2.75; 2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline intake OR 1.91, 95% CI 1.16 to 3.16; and 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine intake OR 2.14, 95% CI 1.31 to 3.49).The data suggest that rapid N-acetylators with high HAA intake may be at increased risk of adenoma.

SUBMITTER: Voutsinas J

PROVIDER: S-EPMC4491437 | biostudies-other | 2013 Mar

REPOSITORIES: biostudies-other

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Heterocyclic amine intake, smoking, cytochrome P450 1A2 and N-acetylation phenotypes, and risk of colorectal adenoma in a multiethnic population.

Voutsinas Jenna J Wilkens Lynne R LR Franke Adrian A Vogt Thomas M TM Yokochi Lance A LA Decker Robert R Le Marchand Loïc L

Gut 20120524 3

<h4>Objective</h4>Heterocyclic amines (HAA) are animal carcinogens that are present in meat cooked at high temperature and in tobacco smoke. These compounds require activation by cytochrome P450 1A2 (CYP1A2) and N-acetyltransferase-2 (NAT2) before they can damage DNA. This study tested the hypotheses that well-done meat and cigarette smoking increase the risk of adenoma, the precursor to most colorectal cancers, especially in individuals with rapid CYP1A2 and rapid NAT2 activities.<h4>Design</h4 ...[more]

PMID: 22628494

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Project description:INTRODUCTION:Oxylipins are bioactive oxidation products derived from n-6 and n-3 polyunsaturated fatty acids (PUFAs) in the linoleic acid and α-linolenic desaturation pathways. PURPOSE:This study determined if carbohydrate intake during prolonged and intensive cycling countered post-exercise increases in n-6 and n-3 PUFA-derived oxylipins. METHODS:The research design utilized a randomized, crossover, counterbalanced approach with cyclists (N = 20, overnight fasted state, 7:00 am start) who engaged in four 75-km time trials while ingesting two types of bananas (Cavendish, Mini-yellow), a 6% sugar beverage, and water only. Carbohydrate intake was set at 0.2 g/kg every 15 minutes, and blood samples were collected pre-exercise and 0 h-, 0.75 h-,1.5 h-, 3 h-, 4.5 h-, 21 h-, 45 h-post-exercise. Oxylipins were measured with a targeted liquid chromatography-multiple reaction monitoring mass spectrometric method. RESULTS:Significant time effects and substantial fold-increases (immediately post-exercise/pre-exercise) were measured for plasma levels of arachidonic acid (ARA), eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA), and 43 of 45 oxylipins. Significant interaction effects (4 trials x 8 time points) were found for plasma ARA (P<0.001) and DHA (P<0.001), but not EPA (P = 0.255), with higher post-exercise values found in the water trial compared to the carbohydrate trials. Significant interaction effects were also measured for 12 of 45 oxylipins. The data supported a strong exercise-induced increase in plasma levels of these oxylipins during the water trial, with carbohydrate ingestion (both bananas types and the sugar beverage) attenuating oxylipin increases, especially those (9 of 12) generated from the cytochrome P-450 (CYP) enzyme system. These trials differences were especially apparent within the first three hours of recovery from the 75-km cycling bout. CONCLUSIONS:Prolonged and intensive exercise evoked a transient but robust increase in plasma levels of oxylipins, with a significant attenuation effect linked to acute carbohydrate ingestion for 28% of these, especially those generated through the CYP enzyme system. TRIAL REGISTRATION:ClinicalTrials.gov, U.S. National Institutes of Health, NCT02994628.

Dataset Information

Heterocyclic amine intake, smoking, cytochrome P450 1A2 and N-acetylation phenotypes, and risk of colorectal adenoma in a multiethnic population.

Publications

Heterocyclic amine intake, smoking, cytochrome P450 1A2 and N-acetylation phenotypes, and risk of colorectal adenoma in a multiethnic population.

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