Epidemiological and mechanistic evidence on the association of
quercetin-rich food intake with
lung cancer risk and
carcinogenesis are inconclusive. We investigated the role of dietary
quercetin and the interaction between
quercetin and P450 and
glutathione S-transferase (GST) polymorphisms on
lung cancer risk in 1822 incident
lung cancer cases and 1991 frequency-matched controls from the Environment And Genetics in
Lung cancer Etiology study. In non-
tumor lung tissue from 38
adenocarcinoma patients, we assessed the correlation between
quercetin intake and
messenger RNA expression of the same P450 and GST metabolic genes. Multivariate odds ratios (
ORs) and 95% confidence intervals (CIs) for sex-specific quintiles of intake were calculated using unconditional logistic regression adjusting for putative risk factors. Frequent intake of
quercetin-rich foods was inversely associated with
lung cancer risk (OR = 0.49; 95% CI: 0.37-0.67; P-trend < 0.001) and did not differ by P450 or GST genotypes, gender or histological subtypes. The association was stronger in subjects who smoked >20 cigarettes per day (OR = 0.35; 95% CI: 0.19-0.66; P-trend = 0.003). Based on a two-sample t-test, we compared gene expression and high versus low consumption of
quercetin-rich foods and observed an overall upregulation of GSTM1, GSTM2, GSTT2, and GSTP1 as well as a downregulation of specific P450 genes (P-values < 0.05, adjusted for age and smoking status). In conclusion, we observed an inverse association of
quercetin-rich food with
lung cancer risk and identified a possible mechanism of
quercetin-related changes in the expression of genes involved in the metabolism of tobacco
carcinogens in humans. Our findings suggest an interplay between
quercetin intake, tobacco smoking, and
lung cancer risk. Further research on this relationship is warranted.