Isothiocyanate exposure, glutathione S-transferase polymorphisms, and colorectal cancer risk.
BACKGROUND
Isothiocyanates, compounds found primarily in cruciferous vegetables, have been shown in laboratory studies to possess anticarcinogenic activity. Glutathione S-transferases (GSTs) are involved in the metabolism and elimination of isothiocyanates; thus, genetic variations in these enzymes may affect in vivo bioavailability and the activity of isothiocyanates.


OBJECTIVE
The objective was to prospectively evaluate the association between urinary isothiocyanate concentrations and colorectal cancer risk as well as the potential modifying effect of GST genotypes on the association.


METHODS
A nested case-control study of 322 cases and 1251 controls identified from the Shanghai Women's Health Study was conducted.


RESULTS
Urinary isothiocyanate concentrations were inversely associated with colorectal cancer risk; the inverse association was statistically significant or nearly significant in the GSTM1-null (P for trend = 0.04) and the GSTT1-null (P for trend = 0.07) genotype groups. The strongest inverse association was found among individuals with both the GSTM1-null and the GSTT1-null genotypes, with an adjusted odds ratio of 0.51 (95% CI: 0.27, 0.95), in a comparison of the highest with the lowest tertile of urinary isothiocyanates. No apparent associations between isothiocyanate concentration and colorectal cancer risk were found among individuals who carried either the GSTM1 or GSTT1 gene (P for interaction < 0.05).


CONCLUSIONS
This study suggests that isothiocyanate exposure may reduce the risk of colorectal cancer, and this protective effect may be modified by the GSTM1 and GSTT1 genes.
Yang
Gong
G
Department of Medicine, Vanderbilt University School of Medicine, Nashville, TN, USA. gong.yang@vanderbilt.edu
Gao
Yu-Tang
YT
Shu
Xiao-Ou
XO
Cai
Qiuyin
Q
Li
Guo-Liang
GL
Li
Hong-Lan
HL
Ji
Bu-Tian
BT
Rothman
Nathaniel
N
Dyba
Marcin
M
Xiang
Yong-Bing
YB
Chung
Fung-Lung
FL
Chow
Wong-Ho
WH
Zheng
Wei
W
D000368:Aged; D001682:Biological Availability; D019607:Brassicaceae / Q000737:chemistry*; D016022:Case-Control Studies; D002681:China; D015179:Colorectal Neoplasms / Q000235:genetics* / Q000652:urine; D004032:Diet; D005260:Female; D005982:Glutathione Transferase / Q000235:genetics*; D006801:Humans; D017879:Isothiocyanates / Q000652:urine*; D008875:Middle Aged; D016017:Odds Ratio; D011110:Polymorphism, Genetic; D012307:Risk Factors; D014675:Vegetables / Q000737:chemistry
D017879:Isothiocyanates; C037152:isothiocyanic acid; D005982:Glutathione Transferase