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Cytosolic sulfotransferases (SULTs) are phase II detoxification enzymes that are involved in the biotransformation of a wide variety of structurally diverse endo- and xenobiotics, including many therapeutic agents and endogenous steroids. Single-nucleotide polymorphisms (SNPs) in SULTs have functional consequences on the translated protein. For the most part, these SNPs are fairly uncommon in the population, but some, most notably for SULT isoform 1A1, are commonly found and have been associated with cancer risk for a variety of tumor sites and also with response to therapeutic agents. SNPs in the hydroxysteroid sulfotransferase, SULT2A1, have been identified in African-American subjects and influence the ratio of plasma DHEA:DHEA-S. This modification could potentially influence cancer risk in steroidogenic tissues. SNPs in many SULTs are ethnically distributed, another factor that could influence SULT pharmacogenetics. Finally, genetic variation has also been identified in 3′-phosphoadenoside 5′-phosphosulfate synthetase (PAPPS), the enzymes responsible for producing the obligatory cosubstrate for all sulfotransferases. Taken together, this variability could substantially influence the disposition of drugs metabolized by SULTs. Elucidation of the basis and effect of variability in sulfation could greatly impact individualized therapy in the future.Oncogene (2006) 25, 1673–1678. doi:10.1038/sj.onc.1209376 [ABSTRACT FROM AUTHOR]

Although cigarette smoking is a clear risk factor for lung cancer, the other determinants of lung cancer risk among smokers are less clear. Tea and coffee contain catechins and flavonoids, which have been shown to exhibit anticarcinogenic properties. Conversely, caffeine may elevate cancer risk through a variety of mechanisms. The current study investigated the effects of regular consumption of black tea and coffee on lung cancer risk among 993 current and former smokers with primary incident lung cancer and 986 age-, sex-, and smoking-matched hospital controls with non-neoplastic conditions. Results indicated that lung cancer risk was not different for those with the highest black tea consumption (>or=2 cups/day) compared with nondrinkers of tea [adjusted odds ratio (aOR)=0.90; 95% confidence interval (CI)=0.66-1.24]. However, elevated lung cancer risk was observed for participants who consumed 2-3 cups of regular coffee daily (aOR=1.34; 95% CI=0.99-1.82) or >or=4 cups of regular coffee daily (aOR=1.51, 95% CI=1.11-2.05). In contrast, decaffeinated coffee drinking was associated with decreased lung cancer risk for both participants who consumed or=2 cups/day (aOR=0.64; 95% CI=0.51-0.80). These results suggest that any chemoprotective effects of phytochemicals in coffee and tea may be overshadowed by the elevated risk associated with caffeine in these beverages. [ABSTRACT FROM AUTHOR]

[2-14C]2-amino-1-methyl-phenlimidazo[4,5-b]pyridine ([14C]PhIP), a putative human carcinogenic heterocyclic amine found in well-done cooked meat, was administered orally to three colon cancer patients undergoing a partial colonectomy. Forty-eight to seventy-two hours prior to surgery, subjects received a 70-84 μg dose of 14C. Urine and blood were analyzed by HPLC for PhIP and PhIP metabolites. Metabolites were identified based on HPLC co-elution with authentic PhIP metabolite standards, mass spectral analysis and susceptibility to enzymatic cleavage. In two subjects, 90% of the administered [14CPhIP dose was eliminated in the urine, whereas in the other, only 50% of the dose was found in the urine. One subject excreted three times more radioactivity in the first 4 h than did the others. Twelve radioactive peaks associated with PhIP were detected in the urine samples. The relative amount of each metabolite varied by subject, and the amounts of each metabolite within subjects changed over time. In all three subjects the most abundant urinary metabolite was identified as 2-hydroxyamino-1-methyl-6-phenylimidazo[4,5-b]pyridine- N2-glucuronide (N-hydroxy-PhIP-N2-glucuronide, accounting for 47-60% of the recovered counts in 24 h. PhIP accounted for <1% of the excreted radiolabel in all three patients. Other metabolites detected in the urine at significant amounts were 4-(2-amino-1-methylimidazo[4,5-b]pyrid-6-yl)phenyl sulfate, N-hydroxy-PhIP-N3-glucuronide and PhIP-N2-glucuronide. In the plasma, N-hydroxy-PhIP-N2-glucuronide accounted for 60, 18 and 20% of the recovered plasma radioactivity at 1 h post PhIP dose in subjects 1, 2 and 3 respectively. Plasma PhIP was 56-17% of the recovered dose at 1 h post exposure. The relatively high concentration of N-hydroxy-PhIP-N2-glucuronide and the fact that it is an indicator of bioactivation make this metabolite a potential biomarker for PhIP exposure and activation. Determining the relative differences in PhIP metabolites among individuals will indicate metabolic differences that may predict individual susceptibility to carcinogenic risk from this suspected dietary carcinogen. [ABSTRACT FROM PUBLISHER]