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

• Published in: The Lancet (British edition) Vol. 356; no. 9231; pp. 724 - 729
• Main Authors: London, Stephanie J, Yuan, Jian-Min, Chung, Fung-Lung, Gao, Yu-Tang, Coetzee, Gerhard A, Ross, Ronald K, Yu, Mimi C
• Format: Journal Article
• Language: English
• Published: London Elsevier Ltd 26.08.2000; Lancet; Elsevier Limited
• Subjects: Analysis. Health state; Biological and medical sciences; Carcinogenesis; Case-Control Studies; China - epidemiology; Enzymatic activity; Enzymes; Epidemiology; Excretion; General aspects; Genotype; Genotypes; Glutathione Transferase - genetics; Glutathione Transferase - isolation & purification; Health risk assessment; Health risks; Humans; Isothiocyanates - urine; Logistic Models; Lung cancer; Lung Neoplasms - epidemiology; Lung Neoplasms - mortality; Lung Neoplasms - urine; Male; Medical research; Medical sciences; Men; Middle Aged; Pneumology; Polymerase Chain Reaction; Polymorphism, Genetic; Prospective Studies; Public health. Hygiene; Public health. Hygiene-occupational medicine; Risk Factors; Risk reduction; Smoking - adverse effects; Tumors of the respiratory system and mediastinum; Urine; Asia; China; Shanghai China; Human; Urine; Lung disease; Respiratory disease; Enzyme; Transferases; Lung; Male; Malignant tumor; Genetic determinism; Epidemiology; Assay; Follow up study; Glutathione transferase; Risk factor; Predisposition; Adult; Isothiocyanates; Public health; Comparative study
• ISSN: 0140-6736; 1474-547X
• DOI: 10.1016/S0140-6736(00)02631-3

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. 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. Individuals with detectable isothiocyanates in the urine were at decreased risk of lung cancer (smoking-adjusted relative risk for lung cancer=0·65 [95% Cl 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]). 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.