Dietary Intake of Isothiocyanates: Evidence of a Joint Effect with Glutathione S-Transferase Polymorphisms in Lung Cancer Risk
Isothiocyanates (ITCs) are nonnutrient compounds in cruciferous vegetables with anticarcinogenic properties. One proposed mechanism for their protective action is through down-regulation of cytochrome P-450 biotransformation enzyme levels and induction of phase II detoxifying enzymes. Because ITCs a...
Saved in:
Published in | Cancer epidemiology, biomarkers & prevention Vol. 9; no. 10; pp. 1017 - 1020 |
---|---|
Main Authors | , , , , , , , , , |
Format | Journal Article |
Language | English |
Published |
Philadelphia, PA
American Association for Cancer Research
01.10.2000
|
Subjects | |
Online Access | Get full text |
Cover
Loading…
Summary: | Isothiocyanates (ITCs) are nonnutrient compounds in cruciferous
vegetables with anticarcinogenic properties. One proposed mechanism for
their protective action is through down-regulation of cytochrome P-450
biotransformation enzyme levels and induction of phase II detoxifying
enzymes. Because ITCs also serve as a substrate for
GSTs , we evaluated dietary intake of ITCs and
GSTM1 and GSTT1 genotype information in a
lung cancer case-control study. There were 503 newly diagnosed lung
cancer cases (264 men and 239 women) identified from The University of
Texas M. D. Anderson Cancer Center and 465 controls (252 men and 213
women) recruited from enrollees in a local managed care organization.
Subjects had an in-person interview including a semiquantitative food
frequency questionnaire, and blood samples were obtained for
genotyping. Cases reported significantly lower ITC intake per day
compared with controls ( P = 0.009). There was no
main effect associated with the GSTM1 null genotype[
odds ratio (OR) = 1.09]. However, there was a statistically
significant OR of 1.41 associated with the GSTT1 null
genotype. On stratified analysis, low ITC intake and the
GSTM1 null genotype were associated with increased lung
cancer risk in current smokers, with an OR of 2.22 [confidence
interval (CI) = 1.20–4.10). For current smokers with the
GSTT1 null genotype, the OR with low ITC intake was 3.19
(CI = 1.54–6.62). The comparable OR in the presence of both null
genotypes was 5.45 (CI = 1.72–17.22). These effects were
not demonstrable for former smokers by GSTM1 genotype,
although the risk for low ITC intake and GSTT1 null
genotype was 1.79 (CI = 0.95–3.37). Thus, current smokers
who are homozygous null for the GST null genotype and
who consume less carcinogenic blocking compounds are at higher lung
cancer risk. Some of the inconsistencies reported in the role of
GST genotypes in lung cancer risk could be due to
unexpected confounding from dietary factors. |
---|---|
ISSN: | 1055-9965 1538-7755 |