Flavonols and Pancreatic Cancer Risk
The Multiethnic Cohort Study
Ute No ¨thlings1,2, Suzanne P. Murphy1, Lynne R. Wilkens1, Brian E. Henderson3, and
Laurence N. Kolonel1
1Cancer Research Center of Hawaii, University of Hawaii, Honolulu, HI.
2Department of Epidemiology, German Institute of Human Nutrition Potsdam-Rehbruecke, Nuthetal, Germany.
3Department of Preventive Medicine, Keck School of Medicine, University of Southern California, Los Angeles, CA.
Received for publication February 15, 2007; accepted for publication May 8, 2007.
Only a few prospective studies have investigated flavonols as risk factors for cancer, none of which has included
pancreatic cancer. The latter is usually fatal, rendering knowledge about prevention particularly important. The
authors estimated intakes of three flavonols—quercetin, kaempferol, and myricetin—for 183,518 participants in the
Multiethnic Cohort Study and examined associations with incidence of pancreatic cancer. Baseline data were
collected in Hawaii and California in 1993–1996. Diet was assessed by using a quantitative food frequency
questionnaire. During 8 years of follow-up, 529 cases of exocrine pancreatic cancer occurred. Multivariate Cox
regressionmodelswerecalculatedtoestimaterelativerisks. Intakeoftotalflavonolswasassociatedwitha reduced
pancreatic cancer risk (relative risk for the highest vs. lowest quintile ¼ 0.77, 95% confidence interval: 0.58, 1.03;
p trend ¼ 0.046). Of the three individual flavonols, kaempferol was associated with the largest risk reduction
(relative risk ¼ 0.78, 95% confidence interval: 0.58, 1.05; p trend ¼ 0.017). Total flavonols, quercetin, kaempferol,
and myricetin were all associated with a significant inverse trend among current smokers (relative risks for the
highest vs. lowest quartile ¼ 0.41, 0.55, 0.27, 0.55, respectively) but not never or former smokers. This study
provides evidence for a preventive effect of flavonols on pancreatic cancer, particularly for current smokers.
diet; flavonols; pancreatic neoplasms; prospective studies
Flavonols are a class of flavonoids, polyphenols, which
are ubiquitous in plant foods and may exert cancer preven-
tive effects (1, 2). Major sources of flavonols are onions,
curly kale, leeks, broccoli, apples, and blueberries (3). Other
classes of flavonoids include flavanols, anthocyanins,
flavanones, and isoflavones (2). Anticarcinogenic effects
in animals and in vitro studies have been attributed to
the ability of these constituents to inhibit the cell cycle, cell
proliferation, and oxidative stress and to induce detoxifica-
tion enzymes and apoptosis (4–6). However, evidence from
human population studies is scarce (2) and has been
hampered primarily by a lack of coverage of flavonols, as
well as flavonoids in general, in food composition
Recent reviews of epidemiologic studies concluded that
the evidence was limited for an inverse association between
polyphenol intake and cancer risk (8, 9). The most consis-
tent inverse association was found between flavonols, espe-
cially quercetin, and lung cancer. None of the studies with
flavonols included pancreatic cancer. Because of a 5-year
survival rate of less than 5 percent, pancreatic cancer is one
of the most fatal cancers, and research into disease preven-
tion is greatly needed (10). Smoking is the only established
risk factor for pancreatic cancer so far. A family history of
pancreatic cancer, a diagnosis of diabetes mellitus, and obe-
sity have also been associated with the disease. Other risk
factors include age, male sex, and Native Hawaiian or
African-American ethnicity (11–15).
Correspondence to Dr. Ute No ¨thlings, Department of Epidemiology, German Institute of Human Nutrition Potsdam-Rehbruecke,
Arthur-Scheunert Allee 114-116, 14558 Nuthetal, Germany (e-mail: email@example.com).
924 Am J Epidemiol 2007;166:924–931
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Vol. 166, No. 8
Advance Access publication August 9, 2007
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