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Am J Clin Nutr 91: 704-711, 2010. First published December 30, 2009; doi:10.3945/ajcn.2009.28683
 American Journal of Clinical Nutrition, doi:10.3945/ajcn.2009.28683
Vol. 91, No. 3, 704-711, March 2010
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© 2010 American Society for Clinical Nutrition

ORIGINAL RESEARCH COMMUNICATION

Isothiocyanate exposure, glutathione S-transferase polymorphisms, and colorectal cancer risk1,2,3,4

Gong Yang, Yu-Tang Gao, Xiao-Ou Shu, Qiuyin Cai, Guo-Liang Li, Hong-Lan Li, Bu-Tian Ji, Nathaniel Rothman, Marcin Dyba, Yong-Bing Xiang, Fung-Lung Chung, Wong-Ho Chow and Wei Zheng

1 From the Division of Epidemiology Department of Medicine Vanderbilt Epidemiology Center Vanderbilt-Ingram Cancer Center Vanderbilt University School of Medicine Nashville TN (GY X-OS QC G-LLWZ); the Shanghai Cancer Institute Shanghai China (Y-TG H-LLY-BX); the Division of Cancer EpidemiologyGenetics National Cancer Institute National Institutes of Health DHHS Bethesda MD (B-TJ NRW-HC);the Lombardi Comprehensive Cancer Center Georgetown University Washington DC (MDF-LC).

2 The contents are solely the responsibility of the authors and do not necessarily represent the official views of the National Institutes of Health.

3 Supported by USPHS grant R01CA70867. The Shanghai Women's Health Study was supported in part by the NIH Intramural Research Program (N02 CP1101066). GY was supported in part by USPHS grant R01CA 122364. The biospecimens were prepared at the Survey and Biospecimen Shared Resource, which is supported in part by P30CA68485.

4 Address correspondence to G Yang, Division of Epidemiology, Department of Medicine, Vanderbilt University School of Medicine, Sixth Floor, Suite 600, 2525 West End Avenue, Nashville, TN 37203-1738. E-mail: gong.yang{at}vanderbilt.edu.

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.

Design: 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).

Conclusion: 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.