Glutathione S-transferase polymorphisms, cruciferous vegetable intake and cancer risk in the Central and Eastern European Kidney Cancer Study.
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 GSTM1 deletion, GSTM3 3 bp deletion (IVS6 + 22-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 (less than once per 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.
Moore
L E
LE
Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Department of Health and Human Services, Bethesda, MD 20892, USA. moorele@mail.nih.gov
Brennan
P
P
Karami
S
S
Hung
R J
RJ
Hsu
C
C
Boffetta
P
P
Toro
J
J
Zaridze
D
D
Janout
V
V
Bencko
V
V
Navratilova
M
M
Szeszenia-Dabrowska
N
N
Mates
D
D
Mukeria
A
A
Holcatova
I
I
Welch
R
R
Chanock
S
S
Rothman
N
N
Chow
W-H
WH
D000328:Adult; D000368:Aged; D019607:Brassicaceae; D004247:DNA / Q000097:blood / Q000235:genetics / Q000302:isolation & purification; D005060:Europe / Q000453:epidemiology; D005061:Europe, Eastern / Q000453:epidemiology; D005247:Feeding Behavior; D005260:Female; D005838:Genotype; D005982:Glutathione Transferase / Q000235:genetics*; D006801:Humans; D007407:Interviews as Topic; D007680:Kidney Neoplasms / Q000453:epidemiology* / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D011110:Polymorphism, Genetic; D020641:Polymorphism, Single Nucleotide; D012307:Risk Factors; D017384:Sequence Deletion; D014675:Vegetables
D004247:DNA; D005982:Glutathione Transferase