Dietary quercetin, quercetin-gene interaction, metabolic gene expression in lung tissue and lung cancer risk.
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.
Lam
Tram Kim
TK
Cancer Prevention Fellowship Program, Office of Preventive Oncology, National Cancer Institute, National Institutes of Health, Department of Health and Human Services, Bethesda, MD 20892, USA.
Rotunno
Melissa
M
Lubin
Jay H
JH
Wacholder
Sholom
S
Consonni
Dario
D
Pesatori
Angela C
AC
Bertazzi
Pier Alberto
PA
Chanock
Stephen J
SJ
Burdette
Laurie
L
Goldstein
Alisa M
AM
Tucker
Margaret A
MA
Caporaso
Neil E
NE
Subar
Amy F
AF
Landi
Maria Teresa
MT
D000368:Aged; D016022:Case-Control Studies; D003577:Cytochrome P-450 Enzyme System / Q000235:genetics*; D005260:Female; D005638:Fruit; D005982:Glutathione Transferase / Q000235:genetics*; D006801:Humans; D008168:Lung / Q000378:metabolism*; D008175:Lung Neoplasms / Q000209:etiology*; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D011794:Quercetin / Q000008:administration & dosage*; D012307:Risk Factors; D014675:Vegetables
D003577:Cytochrome P-450 Enzyme System; D011794:Quercetin; D005982:Glutathione Transferase