Intake of flavonoids and lung cancer.
BACKGROUND
To investigate the possible relationship between intake of flavonoids-powerful dietary antioxidants that may also inhibit P450 enzymes-and lung cancer risk, we conducted a population-based, case-control study in Hawaii.


METHODS
An in-person interview assessed smoking history and usual intake of 242 food items for 582 patients with incident lung cancer and 582 age-, sex-, and ethnicity-matched control subjects. Subjects who donated a blood sample were genotyped for the P450 enzyme variant allele CYP1A1*2 by use of a polymerase chain reaction-based method. Logistic regression analysis was used to compute odds ratios (ORs) and 95% confidence intervals (CIs). All P values are two-sided.


RESULTS
After adjusting for smoking and intakes of saturated fat and beta-carotene, we found statistically significant inverse associations between lung cancer risk and the main food sources of the flavonoids quercetin (onions and apples) and naringin (white grapefruit). The lung cancer OR for the highest compared with the lowest quartile of intake was 0.5 (95% CI = 0.3-0.9) for onions (P for trend =.001) and 0.6 (95% CI = 0.4-1.0) for apples (P for trend =.03). The OR for the highest compared with the lowest tertile of intake for white grapefruit was 0.5 (95% CI = 0.2-0.9) (P for trend =.02). No association was found for important food sources of other flavonoids. Using published food-composition data for flavonoids, we found an inverse association between intake of quercetin and risk of lung cancer (P for trend =.07) that appears consistent with associations for its food sources. The effect of onions was particularly strong against squamous cell carcinoma (a cell type specifically associated with CYP1A1*2 in our study) and was modified by the CYP1A1 genotype, suggesting that CYP1A1 may play a role in this association.


CONCLUSIONS
If replicated, particularly in prospective studies, these findings would suggest that foods rich in certain flavonoids may protect against certain forms of lung cancer and that decreased bioactivation of carcinogens by inhibition of CYP1A1 should be explored as underlying mechanisms.
Le Marchand
L
L
Etiology Program, Cancer Research Center of Hawaii, University of Hawaii, Honolulu 96813, USA. loic@crch.hawaii.edu
Murphy
S P
SP
Hankin
J H
JH
Wilkens
L R
LR
Kolonel
L N
LN
D000368:Aged; D000975:Antioxidants / Q000008:administration & dosage; D016022:Case-Control Studies; D019363:Cytochrome P-450 CYP1A1 / Q000235:genetics*; D005247:Feeding Behavior; D005260:Female; D044950:Flavanones; D005419:Flavonoids / Q000008:administration & dosage*; D005838:Genotype; D006254:Hawaii; D006801:Humans; D016015:Logistic Models; D008175:Lung Neoplasms / Q000201:enzymology / Q000517:prevention & control*; D008297:Male; D008875:Middle Aged; D015596:Nutrition Assessment; D016017:Odds Ratio; D016133:Polymerase Chain Reaction; D011110:Polymorphism, Genetic; D011794:Quercetin / Q000008:administration & dosage
D000975:Antioxidants; D044950:Flavanones; D005419:Flavonoids; D011794:Quercetin; D019363:Cytochrome P-450 CYP1A1; C005274:naringin