Tobacco smoking is a risk factor for colorectal cancer and adenomas. To clarify the effect of genetic factors on the risk for tobacco-related colorectal tumors in a Japanese population, we performed a case-control study on 300 patients with two or more tumors and 181 healthy controls; all were genotyped for CYP2A6*4, CYP2A6*7 and CYP2A6*9. Cigarette smoking increased colorectal tumor risk (tren...

In humans, 80% of nicotine is metabolized to the inactive metabolite cotinine by the enzyme CYP2A6, which can also activate tobacco smoke procarcinogens (e.g., 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone). Previously, we demonstrated that individuals who are nicotine-dependent and have defective CYP2A6 alleles (*2, *3) smoked fewer cigarettes; however, we recognize that the genotyping method...

Overview: Cigarette smoking is responsible for numerous health problems, including cancer and cardiovascular and pulmonary disorders. It is the leading cause of preventable deaths worldwide. Nicotine is primarily responsible for the highly addictive properties of cigarettes. In humans, nicotine is mainly inactivated into cotinine, and the hepatic enzyme cytochrome P450 2A6 (CYP2A6) mediates the...

introduction: nicotine is the psychoactive substance responsible for establishing and maintaining smoking dependence. cyp2a6 is the primary enzyme that inactivates nicotine to cotinine .genetic variation in cyp2a6 accounts for some of the inter-individual variability in nicotine metabolism and has been indicated to influence smoking behavior and dependence. therefore, the aim of this study was ...

In a caffeine test previously performed with healthy Japanese volunteers, we found that the CYP1A2 index defined as urinary {5-acetylamino-6-amine-3-methyluracil (AAMU)+1-methylxanthine (1X)+1-methyluric acid (1 U)}/1,7-dimethyluric acid (17 U) was affected by the whole deleted allele of CYP2A6 (CYP2A6*4). Since the high value of the CYP1A2 index could be caused by a low urinary concentration o...

BACKGROUND Cotinine, a nicotine metabolite, is a biomarker of tobacco, nicotine, and carcinogen exposure. However, a given cotinine level may not represent the same tobacco exposure; for example, African-Americans have higher cotinine levels than Caucasians after controlling for exposure. METHODS Cotinine levels are determined by the amount of cotinine formation and the rate of cotinine remov...

Human CYP2A6, which is predominantly expressed in liver, is a key enzyme responsible for the metabolism of nicotine, coumarin, and some pharmaceutical drugs. CYP2A6 is also expressed in sex steroid-responsive tissues such as breast, ovary, uterus, testis, and adrenal grand. In this study, we examined the regulation of CYP2A6 gene by estrogen. Reverse transcription-polymerase chain reaction (RT-...

CYP2A6 is the principle enzyme metabolizing nicotine to its inactive metabolite cotinine. In this study, the selective probe reactions for each major cytochrome P450 (P450) were used to evaluate the specificity and selectivity of the CYP2A6 inhibitors methoxsalen, tranylcypromine, and tryptamine in cDNA-expressing and human liver microsomes. Phenacetin O-deethylation (CYP1A2), coumarin 7-hydrox...

Nicotine C-oxidation is primarily catalyzed by CYP2A6 in humans. This enzymatic activity exhibits a large interindividual variability, which to a great extent is caused by genetic polymorphisms in the CYP2A6 gene. There are large interindividual differences in CYP2A6 mRNA and protein levels, but little is known about the transcriptional regulation of CYP2A6, which can, e.g., explain such differ...