Cancer Causes & Control

, Volume 15, Issue 10, pp 977–985 | Cite as

Dietary intake of Cruciferous vegetables, Glutathione S-transferase (GST) polymorphisms and lung cancer risk in a Caucasian population

  • Lisa I. Wang
  • Edward L. Giovannucci
  • David Hunter
  • Donna Neuberg
  • Li Su
  • David C. Christiani


Objective: To evaluate possible interactions between dietary intake of cruciferous vegetables and the glutathione s-transferase mu and theta (GSTM1 and GSTT1) genotypes in lung cancer risk.

Methods: Hospital-based case–control study of 716 Caucasian lung cancer cases and 939 spouse and friend controls conducted in Boston, Massachussetts between 1992 and 2000. Dietary intake was collected through a food frequency questionnaire and blood was obtained for genotyping. Logistic regression models were adjusted for age, gender, total calories and smoking variables.

Results: Higher intakes of cruciferous vegetables reduced lung cancer risk among GSTM1 present individuals (odds ratio (OR) highest versus lowest tertile = 0.61, 95% confidence interval (CI) = 0.39–0.95) but not among GSTM1 null individuals (OR highest versus lowest tertile = 1.15, 95% CI = 0.78–1.68). We observed statistically significant interactions between GSTM1 and cruciferous vegetable intake overall (likelihood ratio test (LRT): p = 0.05) and among current smokers (LRT: p = 0.01). No significant interactions were observed for GSTT1 or the combined GSTM1/T1 genotype.

Conclusions: In our study, higher cruciferous vegetable intake reduced lung cancer risk only among individuals with the GSTM1 present genotype. Our findings differed from prior studies that specifically assessed isothiocyanates found in cruciferous vegetables or evaluated Asian study populations with higher levels of cruciferous vegetable consumption.

cruciferous vegetables GSTM1 GSTT1 lung cancer gene-environment interaction 


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  1. 1.
    Verhoeven DT, Goldbohm RA, van Poppel G, Verhagen H, van den Brandt, PA (1996) Epidemiological studies on brassica vegetables and cancer risk. Cancer Epidemiol Biomarkers Prev 5: 733–748.Google Scholar
  2. 2.
    Hecht SS (1999) Chemoprevention of cancer by isothiocyanates, modi ers of carcinogen metabolism. J Nutr 129: 768S–774S.Google Scholar
  3. 3.
    Zhang Y, Talalay P, Cho CG, Posner, GH (1992) A major inducer of anticarcinogenic protective enzymes from broccoli: Isolation and elucidation of structure. Proc Natl Acad Sci USA 89: 2399–2403.Google Scholar
  4. 4.
    Miller MS, McCarver DG, Bell DA, Eaton DL, Goldstein JA (1997) Genetic polymorphisms in human drug metabolic enzymes. Fundam Appl Toxicol 40: 1–14.Google Scholar
  5. 5.
    Hecht SS (1999) Tobacco smoke carcinogens and lung cancer. J Natl Cancer Inst 91: 1194–1210.Google Scholar
  6. 6.
    Houlston RS (1999) Glutathione S-transferase M1 status and lung cancer risk: A meta-analysis. Cancer Epidemiol Biomarkers Prev 8: 675–682.Google Scholar
  7. 7.
    Rebbeck TR (1997) Molecular epidemiology of the human glutathione S-transferase genotypes GSTM1 and GSTT1 in cancer susceptibility. Cancer Epidemiol Biomarkers Prev 6: 733–743.Google Scholar
  8. 8.
    Shapiro TA, Fahey JW, Wade KL, Stephenson KK, Talalay P (1998) Human metabolism and excretion of cancer chemoprotec-tive glucosinolates and isothiocyanates of cruciferous vegetables. Cancer Epidemiol Biomarkers Prev 7: 1091–1100.Google Scholar
  9. 9.
    Zhang Y, Kolm RH, Mannervik B, Talalay P (1995) Reversible conjugation of isothiocyanates with glutathione catalyzed by human glutathione transferases. Biochem Biophys Res Commun 206: 748–755.Google Scholar
  10. 10.
    Lin HJ, Probst-Hensch NM, Louie AD, et al. (1998) Glutathione transferase null genotype, broccoli, and lower prevalence of colo-rectal adenomas. Cancer Epidemiol Biomarkers Prev 7: 647–652.Google Scholar
  11. 11.
    Ye L, Zhang Y (2001) Total intracellular accumulation levels of dietary isothiocyanates determine their activity in elevation of cellular glutathione and induction of Phase 2 detoxi cation enzymes. Carcinogenesis 22: 1987–1992.Google Scholar
  12. 12.
    London SJ, Yuan JM, Chung FL, et al. (2000) Isothiocyanates, glutathione S-transferase M1 and T1 polymorphisms, and lung-cancer risk:a prospective study of men in Shanghai, China. Lancet 356: 724–729.Google Scholar
  13. 13.
    Spitz MR, Duphorne CM, Detry MA, et al. (2000) Dietary intake of isothiocyanates: evidence of a joint effect with glutathione S-transferase polymorphisms in lung cancer risk. Cancer Epidemiol Biomarkers Prev 9: 1017–1020.Google Scholar
  14. 14.
    Lewis S, Brennan P, Nyberg F, et al. (2001) Re: Spitz MR, Duphorne CM, Detry MA, Pillow PC, Amos CI, Lei L, de Andrade M, Gu X, Hong WK, and Wu X. Dietary intake of isothiocyanates: evidence of a joint effect with glutathione S-trans-ferase polymorphisms in lung cancer risk. Cancer Epidemiol Biomark Prev 9: 1017–1020;2000. Cancer Epidemiol Biomarkers Prev 10: 1105–1106.Google Scholar
  15. 15.
    Zhao B, Seow A, Lee EJ, et al. (2001) Dietary isothiocyanates, glutathione S-transferase-M1,-T1 polymorphisms and lung cancer risk among Chinese women in Singapore. Cancer Epidemiol Biomarkers Prev 10: 1063–1067.Google Scholar
  16. 16.
    Ferris BG (1978) Epidemiology Standardization Project (American Thoracic Society). Am Rev Respir Dis 118: 1–120.Google Scholar
  17. 17.
    Liu G, Miller DP, Zhou W, et al. (2001) Differential association of the codon 72 p53 and GSTM1 polymorphisms on histological subtype of non-small cell lung carcinoma. Cancer Res 61: 8718–8722.Google Scholar
  18. 18.
    Willett WC, Sampson L, Stampfer MJ, et al. (1985) Reproduc-ibility and validity of a semiquantitative food frequency question-naire. Am J Epidemiol 122: 51–65.Google Scholar
  19. 19.
    Rimm EB, Giovannucci EL, Stampfer MJ, Colditz GA, Litin LB, Willett WC (1992) Reproducibility and validity of an expanded self-administered semiquantitative food frequency questionnaire among male health professionals. Am J Epidemiol 135: 1114–1126; discussion 1127–1136.Google Scholar
  20. 20.
    Colditz GA, Willett WC, Stampfer MJ, et al. (1987) The influence of age, relative weight, smoking, and alcohol intake on the reproducibility of a dietary questionnaire. Int J Epidemiol 16: 392–398.Google Scholar
  21. 21.
    Feskanich D, Ziegler RG, Michaud DS, et al. (2000) Prospective study of fruit and vegetable consumption and risk of lung cancer among men and women. J Natl Cancer Inst 92: 1812–1823.Google Scholar
  22. 22.
    Zhou W, Thurston SW, Liu G, et al. (2001) The interaction between microsomal epoxide hydrolase polymorphisms and cumu-lative cigarette smoking in different histological subtypes of lung cancer. Cancer Epidemiol Biomarkers Prev 10: 461–466.Google Scholar
  23. 23.
    Foppa I, Spiegelman D (1997) Power and sample size calculations for case–control studies of gene-environment interactions with a polytomous exposure variable [published erratum appears in Am J Epidemiol 1998 Feb 15;147 (4):414 ][see comments]. Am J Epidemiol 146: 596–604.Google Scholar
  24. 24.
    Seow A, Shi CY, Chung FL, et al. (1998) Urinary total isothio-cyanate (ITC)in a population-based sample of middle-aged and older Chinese in Singapore: relationship with dietary total ITC and glutathione S-transferase M1/T1/P1 genotypes. Cancer Epidemiol Biomarkers Prev 7: 775–781.Google Scholar
  25. 25.
    Davis FG, Fischer ME, VanHorn L, Mermelstein RM, Sylvester JL (1993) Self-reported dietary changes with respect to American Cancer Society nutrition guidelines (1982–1986). Nutr Cancer 20: 241–249.Google Scholar
  26. 26.
    Lampe JW, Peterson S (2002) Brasscia, Biotransformation and cancer risk: Genetic polymorphisms alter the preventive effects of cruciferous vegetables. J Nutri 132: 2991–2994.Google Scholar
  27. 27.
    Garcia-Closas M, Thompson WD, Robins JM (1998) Differential misclassi cation and the assessment of gene-environment interac-tions in case–control studies. Am J Epidemiol 147: 426–433.Google Scholar
  28. 28.
    Garcia-Closas M, Rothman N, Lubin J (1999) Misclassi cation in case–control studies of gene-environment interactions: Assessment of bias and sample size. Cancer Epidemiol Biomarkers Prev 8: 1043–1050.Google Scholar

Copyright information

© Kluwer Academic Publishers 2004

Authors and Affiliations

  • Lisa I. Wang
  • Edward L. Giovannucci
  • David Hunter
  • Donna Neuberg
  • Li Su
  • David C. Christiani

There are no affiliations available

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