Flavonoid Intake and Risk of Pancreatic Cancer in Male Smokers (Finland)

Abstract

Extending research on the protective effect of flavonoids in cell culture and animal studies, we examined the association between consumption of flavonoids and flavonoid-rich foods and development of exocrine pancreatic cancer within the A-Tocopherol, B-Carotene Cancer Prevention Study cohort. Of the 27,111 healthy male smokers (50-69 years) who completed a selfadministered dietary questionnaire at baseline, 306 developed exocrine pancreatic cancer during follow-up (1985-2004; median, 16.1 years). Intakes of total flavonoids, three flavonoid subgroups, seven individual flavonoids, and flavonoid-rich foods were estimated from a validated food frequency questionnaire. Hazard ratios and 95% confidence intervals were estimated using Cox proportional hazards models. Overall, flavonoid intake was not significantly associated with pancreatic cancer. However, in stratified analysis, greater total flavonoid intake was associated with decreased pancreatic cancer risk in participants randomized during the trial to placebo (fourth versus first quartile: hazard ratio, 0.36; 95% confidence interval, 0.17-0.78; P trend = 0.009) and not to supplemental A-tocopherol (50 mg/d) and/or B-carotene (20 mg/d; P interaction = 0.002). Similar patterns and significant interactions were observed for flavonols, flavan-3-ols, kaempferol, quercetin, catechin, and epicatechin. Our data suggest that a flavonoid-rich diet may decrease pancreatic cancer risk in male smokers not consuming supplemental A-tocopherol and/or B-carotene. (Cancer Epidemiol Biomarkers Prev 2008;17(3):553-62)

Disposition of Flavonoids via Enteric Recycling: UDP-Glucuronosyltransferase (UGT) 1As Deficiency in Gunn Rats Is Compensated by Increases in UGT2Bs Activities

“…Flavonoids hold great promise as agents to improve human health because epidemiological studies have shown protective effects associated with flavonoid consumption against coronary heart diseases (Arts and Hollman, 2005), stroke (Keli et al, 1996), and lung and colorectal cancers (Hirvonen et al, 2001;Bobe et al, 2008). Currently, several clinical trials are ongoing to test the anticancer efficacy of soy isoflavones and green tea, both of which contain flavonoids as the active ingredients (Crowell, 2005).…”

Flavonoid and lignan intake and pancreatic cancer risk in the European prospective investigation into cancer and nutrition cohort

“…A dietary pattern regarded as rich in flavonols was also found to decrease pancreatic cancer risk in smokers participating in the MEC study, but this was not confirmed in a validation study conducted within the EPIC cohort 19. Increasing intake of flavonoids also decreased pancreatic cancer risk in male smokers not consuming supplemental vitamins in the alpha‐tocopherol, beta‐carotene cancer prevention (ATBC) study ( n  = 306 cases) 14. Both were the only studies supporting an inverse association in smokers, which could be ascribed to the known anti‐oxidative effect (inhibition of CYP450 enzymes) elicited by flavonoids 4.…”

“…databases on flavonoids content in food, the number of food items used for the evaluation of intake of flavonoids, and whether the influence of food processing on flavonoids content was taken into consideration 12, 13, 15. In addition, in some studies, fewer flavonoids subclasses were considered to estimate intake of total flavonoids,9, 14, 16 while other studies focused on a single subclass,12, 17 and only few studies considered individual subclasses of flavonoids 14, 15, 18. Only the NIH‐AARP overcame most of these limitations by considering all subclasses of flavonoids (except proanthocyanidins), and accounting for flavonoids values of processed foods and recipes 13.…”

“…A flavonoid‐rich food pattern and the intake of flavonols were both associated with a reduced pancreatic cancer risk in the Multiethnic cohort study (MEC), with this association being more prominent in smokers 17, 19. This finding was, however, not confirmed in a Finnish cohort study, except when smokers not consuming antioxidant supplements were considered 14. The case‐control study conducted in Italy reported an inverse association with pancreatic cancer risk for proanthocyanidin intake 18.…”

“…These studies suggest that flavonoids inhibit proliferation of various pancreatic cancer cell lines through induction of apoptosis and inhibition of cell growth 4. Epidemiological studies examining the association between flavonoids on pancreatic cancer risk include seven prospective studies,9, 12, 13, 14, 15, 16, 17 and one case‐control study 18. A flavonoid‐rich food pattern and the intake of flavonols were both associated with a reduced pancreatic cancer risk in the Multiethnic cohort study (MEC), with this association being more prominent in smokers 17, 19.…”