LIFE-STYLE AND NUTRITIONAL CORRELATES OF CYTOCHROME CYP1A2 ACTIVITY -INVERSE ASSOCIATIONS WITH PLASMA LUTEIN AND ALPHA-TOCOPHEROL

Cytochrome CYP1A2, a liver enzyme responsible for the metabolic activa tion of a number of putative human carcinogens, exhibits wide inter-in dividual 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 sub jects were patients with in-situ colorectal cancer treated by polypect omy and 47 were healthy population controls. Subjects were also admini stered a detailed lifestyle questionnaire, including a quantitative fo od frequency questionnaire, and were assessed for plasma levels of car otenoids, tocopherols, retinol, ascorbic acid, cholesterol and triglyc erides. In a stepwise multiple regression, 27% of the overall variatio n in CYP1A2 activity was explained by seven variables. Plasma lutein e xplained the largest portion of the variance (7%) and was negatively a ssociated with CYP1A2 activity (p < 0.01), as were use of menopausal r eplacement estrogens (p = 0.04), plasma alpha-tocopherol (p = 0.05) an d alcohol consumption (p = < 0.01). Acetaminophen use (p = 0.05), coff ee consumption (p = 0.05) and plasma lycopene (p = 0.06) were positive ly associated with CYP1A2 activity. After adjustment for these variabl es, no association was found between CYP1A2 activity and sex, race, ag e, education, smoking, physical activity, weight, vitamin E supplement s, the other plasma micronutrients measured, and dietary intakes of re d meat, processed meat and cruciferous vegetables. Results were simila r for colorectal cancer cases and controls. Almost two-thirds (73%) of the variability in CYP1A2 activity remained unexplained. This study c onfirms an enhancing effect of acetaminophen and coffee on CYP1A2 acti vity and suggests an inhibitory effect of estrogens, alcohol and food sources of lutein and alpha-tocopherol on this enzyme.