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Cited by 436Glutathione Transferases and PolymorphismsGenomics, phytochemicals, and oxidative stressPharmacogenetics and Drug Metabolism

Isothiocyanates, glutathione S-transferase M1 and T1 polymorphisms, and lung-cancer risk: a prospective study of men in Shanghai, China

London, Stephanie J, Yuan, Jian-Min, Chung, Fung-Lung, Gao, Yu-Tang, Coetzee, Gerhard A, Ross, Ronald K, Yu, Mimi C·2000·The Lancet
DOI 10.1016/s0140-6736(00)02631-3
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Abstract

Background Dietary isothiocyanates inhibit lung carcinogenesis in laboratory animals but human data are limited. Glutathione S-transferases M1 and T1 (GSTM1 and GSTT1) conjugate isothiocyanates leading to more rapid elimination. Common deletion polymorphisms of GSTM1 and GSTT1 abolish enzyme activity. We hypothesised that chemopreventive effects of isothiocyanates might be heightened when enzymes that enhance their elimination are lacking.Methods We examined the relation between total isothiocyanate concentrations in urine, collected before diagnosis, and the subsequent risk of lung cancer among 232 incident cases of lung cancer and 710 matched controls from a cohort of 18,244 men in Shanghai, China, followed from 1986 to 1997. Homozygous deletion of the GSTM1 and GSTT1 genes were determined by PCR.Findings Individuals with detectable isothiocyanates in the urine were at decreased risk of lung cancer (smoking-adjusted relative risk for lung cancer=0.65 [95% CI 0.43-0.97]). This protective effect of isothiocyanates was seen primarily among individuals with homozygous deletion of GSTM1 (0.36 [0.20-0.63]) and particularly with deletion of both GSTM1 and GSTT1 (0.28 [0.13-0.57]).Interpretation Isothiocyanates appeared to reduce lung-cancer risk in this cohort of Chinese men. Reduction in risk was strongest among persons genetically deficient in enzymes that rapidly eliminate these chemopreventive compounds.

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Crossref · 10.1016/s0140-6736(00)02631-3

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  • Biomarkers are useful when little or no food composition data exist, as is often the case for bioactive molecules such as glucosinolates or contaminants such as aflatoxins.

    “Biomarkers are also useful when little or no data exist on food composition, as is often the case for bioactive molecules such as glucosinolates or food contaminants such as aflatoxins (15,16).”

    From The food metabolome: a window over dietary exposure (2014) · cites this paper as [15]

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Authors
London, S. J., Yuan, J.-M., Chung, F.-L., Gao, Y.-T., Coetzee, G. A., Ross, R. K., & Yu, M. C.
Affiliations
  • University of Southern California (US)
  • Institute for Cancer Prevention (US)
  • Shanghai Cancer Institute (CN)
Corresponding author
London, Stephanie J
ORCID
Venue
The Lancet
Publisher
Elsevier BV
Published
2000-08
Volume
356
Issue
9231
Pages
724-729
ISSN
  • 0099-5355 (ISSN-L)
  • 0140-6736
DOI
10.1016/s0140-6736(00)02631-3
OpenAlex
W2099190519
Cited by
436
References
32
Citations by year
2026: 1 · 2025: 2 · 2024: 3 · 2023: 8 · 2022: 3 · 2021: 6 · 2020: 5 · 2019: 13 · 2018: 12 · 2017: 14 · 2016: 8 · 2015: 11 · 2014: 27 · 2013: 21 · 2012: 20
FWCI
9.15
Type
journal article
Language
en
Open access
closed
Licence
www.elsevier.com/tdm/userlicense/1.0/ (tdm)
Locations
  • The Lancet (publishedVersion)
  • PubMed (publishedVersion)
Funders
  • National Institutes of Health
  • National Cancer Institute (R35CA053890, R01-CA43092, R01CA043092, R35-CA53890)
  • National Institute of Environmental Health Sciences (5P30-ES07048, P30ES007048)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Glutathione Transferases and Polymorphisms
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics, phytochemicals, and oxidative stress
  • Life Sciences › Pharmacology, Toxicology and Pharmaceutics › Pharmacology › Pharmacogenetics and Drug Metabolism
Keywords
isothiocyanates, glutathione S-transferase M1, glutathione S-transferase T1, GSTM1 null genotype, GSTT1 deletion, lung cancer risk, chemoprevention, gene-environment interaction, smoking, Chinese men
MeSH terms
China, Genotype, Glutathione Transferase, Humans, Lung Neoplasms, Male, Middle Aged, Polymorphism, Genetic, Prospective Studies, Risk Factors, Smoking, Logistic Models, Case-Control Studies, Polymerase Chain Reaction, Isothiocyanates

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