Carcinogenesis Advance Access published online on July 7, 2007
Carcinogenesis, doi:10.1093/carcin/bgm151
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Glutathione S-transferase polymorphisms, cruciferous vegetable intake, and cancer risk in the Central and Eastern European Kidney Cancer Study
1 Division of Cancer Epidemiology and Genetics, National Cancer Institute, NIH, DHHS, Bethesda, MD, USA
2 International Agency for Research on Cancer, Lyon, France
3 University of California, School of Public Health, Berkeley California
4 Institute of Carcinogenesis, Cancer Research Centre, Moscow, Russia
5 Department of Preventive Medicine, Faculty of Medicine, Palacky University, Olomouc, Czech Republic
6 Institute of Hygiene and Epidemiology, Charles University, First Faculty of Medicine, Prague, Czech Republic
7 Department of Cancer Epidemiology and Genetics, Masaryk Memorial Cancer Institute, Brno, Czech Republic
8 Department of Epidemiology, Institute of Occupational Medicine, Lodz, Poland
9 Institue of Public Health, Bucharest, Romania
10 Core Genotyping Facility at the Advanced Technology Center of the National Cancer Institute, NIH, Department of Health and Human Services
Corresponding Author E-mail: moorele{at}mail.nih.gov
High consumption of cruciferous vegetables has been associated with reduced kidney cancer risk in many studies. Isothiocyanates, thought to be responsible for the chemopreventive properties of this food group, are conjugated to glutathione by glutathione S-transferases (GSTs) before urinary excretion. Modification of this relationship by host genetic factors is unknown. We investigated cruciferous vegetable intake in 1097 cases and 1555 controls enrolled in a multicentric case-control study from the Czech Republic, Poland, Romania, and Russia. To assess possible gene-diet interactions, genotyped cases (N=925) and controls (N=1247) for selected functional or non-synonymous polymorphisms including the GSTM1deletion, GSTM3-three base pair deletion (IVS6 AGG) and V224I G>A substitution, GSTT1 deletion, and the GSTP1 I105V A>G substitution. The odds ratio (OR) for low (less than once per month) versus high (at least once per week) intake of cruciferous vegetables was 1.29 (95% confidence interval (CI): 1.02-1.62; P-trend=0.03). When low intake of cruciferous vegetables (<1/month) was stratified by GST genotype, higher kidney cancer risks were observed among individuals with the GSTT1 null (OR=1.86; 95% CI:1.07-3.23; P-interaction=0.05) or with both GSTM1/T1 null genotypes (OR=2.49; 95% CI:1.08-5.77; P-interaction=0.05). These data provide additional evidence for the role of cruciferous vegetables in cancer prevention among individuals with common, functional genetic polymorphisms.
Received February 26, 2007; revised May 22, 2007; accepted June 26, 2007.
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