Abstract A105: Dietary quercetin, quercetin-gene interaction, metabolic gene expression in lung tissue, and lung cancer risk

Abstract

Abstract Background: Quercetin is a flavonol found in fruits (apple, grape) and vegetables (onion, broccoli). Quercetin possesses anticarcinogenic properties that protect against cancer. However, the epidemiological evidence on the association of quercetin-rich food intake with lung cancer risk is inconclusive, and how quercetin affects lung carcinogenesis in humans is largely unknown. Laboratory analyses have shown that quercetin may inhibit Phase I cytochrome P450s enzymes responsible for the activation of tobacco-related procarcinogens, and induce Phase II glutathione S-transferase (GST) enzymes responsible for the removal of activated carcinogens. Methods: We investigated the role of dietary quercetin and the interaction between quercetin and P450 and GST polymorphisms on lung cancer risk in incident lung cancer cases and matched controls from Environment and Genetics in Lung cancer Etiology (EAGLE), a population-based case-control study including 2100 primary lung cancer cases and 2120 controls. Dietary information and genotype data were available for 1740 cases and 1919 controls. In fresh-frozen non-tumor lung tissue from 38 adenocarcinoma patients, we also assessed the correlation between dietary quercetin intake and mRNA expression of tobacco-related Phase I and Phase II metabolic genes. Multivariable odds ratios (ORs) and 95% confidence intervals (CIs) for sex-specific quintile of intake were calculated using unconditional logistic regression, adjusted for putative risk factors. Two sample t-test was used to assess difference in expression by quercetin-rich consumption status. Results: Frequent intake of quercetin-rich foods was inversely associated with lung cancer risk (ORQ5vsQ1=0.49;95% CI=0.37–0.67; p-trend: <0.001), and did not differ by genotype, gender, or histological subtypes. The association was stronger in subjects who smoked more than 20 cigarettes per day (ORQ5vsQ1=0.35;95% CI=0.19–0.66; p-trend=0.003). The comparison between gene expression and high-versus-low consumption of quercetin-rich foods showed an overall down-regulation of P450 and up-regulation of GST metabolic genes (p-values<0.05) in lung tissue. Conclusions: Quercetin-rich diet was associated with lower risk of lung cancer and with down-regulation of Phase I P450 genes and up-regulation of Phase II GST genes in lung tissue. These findings suggest a possible mechanism for quercetin-related protection against lung cancer risk through quercetin-induced changes in the expression of genes involved in the metabolism of tobacco-carcinogens. Further studies exploring the interplay between quercetin intake, tobacco smoking, and lung cancer risk are warranted. Citation Information: Cancer Prev Res 2010;3(1 Suppl):A105.