Le Marchand L, Franke A A, Custer L, Wilkens L R, Cooney R V
Etiology Program, University of Hawaii, Honolulu 96813, USA.
Pharmacogenetics. 1997 Feb;7(1):11-9. doi: 10.1097/00008571-199702000-00002.
Cytochrome CYP1A2, a liver enzyme responsible for the metabolic activation of a number of putative human carcinogens, exhibits wide inter-individual differences in activity. In order to characterize sources of variability in CYP1A2 activity, we phenotyped (with the caffeine test) 90 subjects of various ethnic backgrounds in Hawaii. Forty-three subjects were patients with in-situ colorectal cancer treated by polypectomy and 47 were healthy population controls. Subjects were also administered a detailed lifestyle questionnaire, including a quantitative food frequency questionnaire, and were assessed for plasma levels of carotenoids, tocopherols, retinol, ascorbic acid, cholesterol and triglycerides. In a stepwise multiple regression, 27% of the overall variation in CYP1A2 activity was explained by seven variables. Plasma lutein explained the largest portion of the variance (7%) and was negatively associated with CYP1A2 activity (p < 0.01), as were use of menopausal replacement estrogens (p = 0.04), plasma alpha-tocopherol (p = 0.05) and alcohol consumption (p = < 0.01). Acetaminophen use (p = 0.05), coffee consumption (p = 0.05) and plasma lycopene (p = 0.06) were positively associated with CYP1A2 activity. After adjustment for these variables, no association was found between CYP1A2 activity and sex, race, age, education, smoking, physical activity, weight, vitamin E supplements, the other plasma micronutrients measured, and dietary intakes of red meat, processed meat and cruciferous vegetables. Results were similar for colorectal cancer cases and controls. Almost two-thirds (73%) of the variability in CYP1A2 activity remained unexplained. This study confirms an enhancing effect of acetaminophen and coffee on CYP1A2 activity and suggests and inhibitory effect of estrogens, alcohol and food sources of lutein and alpha-tocopherol on this enzyme.
细胞色素CYP1A2是一种肝脏酶，负责多种潜在人类致癌物的代谢活化，其活性存在广泛的个体差异。为了确定CYP1A2活性变异性的来源，我们对夏威夷90名不同种族背景的受试者进行了表型分析（采用咖啡因试验）。43名受试者是接受息肉切除术治疗的原位结直肠癌患者，47名是健康人群对照组。受试者还填写了一份详细的生活方式问卷，包括定量食物频率问卷，并对其血浆中类胡萝卜素、生育酚、视黄醇、抗坏血酸、胆固醇和甘油三酯的水平进行了评估。在逐步多元回归分析中，CYP1A2活性总体变异的27%可由7个变量解释。血浆叶黄素解释了最大部分的变异（7%），且与CYP1A2活性呈负相关（p < 0.01），绝经后补充雌激素的使用（p = 0.04）、血浆α-生育酚（p = 0.05）和饮酒量（p = < 0.01）也是如此。对乙酰氨基酚的使用（p = 0.05）、咖啡的摄入量（p = 0.05）和血浆番茄红素（p = 0.06）与CYP1A2活性呈正相关。在对这些变量进行校正后，未发现CYP1A2活性与性别、种族、年龄、教育程度、吸烟、身体活动、体重、维生素E补充剂、所测量的其他血浆微量营养素以及红肉、加工肉和十字花科蔬菜的饮食摄入量之间存在关联。结直肠癌病例组和对照组的结果相似。CYP1A2活性近三分之二（73%）的变异性仍无法解释。本研究证实了对乙酰氨基酚和咖啡对CYP1A2活性有增强作用，并提示雌激素、酒精以及叶黄素和α-生育酚的食物来源对该酶有抑制作用。
