Skip to main content

Advertisement

SpringerLink
Log in

Polymorphic variation of CYP1A1 is associated with the risk of gastric cardia cancer: a prospective case–cohort study of cytochrome P-450 1A1 and GST enzymes

  • Published:
Cancer Causes & Control Aims and scope Submit manuscript

Abstract

Objective: To determine if genetic polymorphisms of CYP1A1, GSTM1, GSTP1, or GSTT1 are associated with an increased risk of developing esophageal squamous cell carcinoma (ESCC), gastric cardia cancer (GCC), or either in a high-risk Asian population.

Methods: We conducted a case-cohort analysis with 5 years of prospective follow-up. The analytical cohort contained 642 individuals who participated in either the Dysplasia Trial (DT) or the General Population (GPT) of the Nutrition Intervention Trials conducted in Linxian, China, and included 131 cases of ESCC and 90 cases of GCC. Genotyping analysis was performed on DNA extracted from red blood cells using a PureGene kit (Gentra Systems, Inc., Minneapolis, MN) and real-time PCR analysis amplification (Taq-Man). Relative risks and 95% confidence intervals were estimated using the case – cohort estimator for the Cox proportional hazards models. p-values from nested models with genotyping variables came from score tests.

Results: The relative risks for developing ESCC, GCC, or either cancer were calculated in the entire analytic cohort for GSTM1, P1*B (A313G), and T1 and CYP1A1*2A (T3801C) and *2C (A2455G) genotypes, and no significant associations were identified. However, because of the difference in cancer risks between the DT (9.3 cases per 1000 person years) and the GPT (5.3 cases), the analytical cohort was stratified by trial; the DT participants who were heterozygous or homozygous for the variant-allele at CYP1A1*2A had a reduced risk for developing GCC (adjusted RR (95%CI) 0.47 (0.23–1.00) p = 0.037).

Conclusions: This study found an association for the CYP1A1*2A variant allele and a reduced risk of GCC in people at high risk for development of this disease. This finding is consistent with previous studies suggesting that substrates for the cytochrome P-450 1A1 metabolic pathway, such as polycyclic aromatic hydrocarbons, may be etiologically significant in this high-risk region.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Similar content being viewed by others

References

  1. Munoz N, Buiatti E (1996) Chemoprevention of oesophageal cancer. IARC Sci Publ 27–33.

  2. Ke L (2002) Mortality and incidence trends from esophagus cancer in selected geographic areas of China circa 1970–90. Int J Cancer 102: 271–274.

    Google Scholar 

  3. Hu N, Dawsey SM, Wu M, et al.(1992) Familial aggregation of oesophageal cancer in Yangcheng County, Shanxi Province, China. Int J Epidemiol 21: 877–882.

    Google Scholar 

  4. Hu N, Dawsey SM, Wu M, Taylor PR (1991) Family history of oesophageal cancer in Shanxi Province, China. Eur J Cancer 27: 1336.

    Google Scholar 

  5. Hu N, Roth MJ, Emmert-Buck MR, et al.(1999) Allelic loss in esophageal squamous cell carcinoma patients with and without family history of upper gastrointestinal tract cancer. Clin Cancer Res 5: 3476–3482.

    Google Scholar 

  6. Yang CS (1980) Research on esophageal cancer in China:a review. Cancer Res 40&: 2633–26

    Google Scholar 

  7. Nebert DW (2000) Drug-metabolizing enzymes, polymorphisms and interindividual response to environmental toxicants. Clin Chem Lab Med 38: 857–861.

    Google Scholar 

  8. Wang AH, Sun CS, Li LS, Huang JY, Chen QS (2002) Relation-ship of tobacco smoking CYP1A1 GSTM1 gene polymorphism and esophageal cancer in Xi' an. World J Gastroenterol 8: 49–53.

    Google Scholar 

  9. Gao C, Takezaki T, Wu J, et al.(2002) Interaction between cytochrome P-450 2E1 polymorphisms and environmental factors with risk of esophageal and stomach cancers in Chinese. Cancer Epidemiol Biomarkers Prev 11: 29–34.

    Google Scholar 

  10. Tan W, Chen GF, Xing DY, Song CY, Kadlubar FF, Lin DX (2001) Frequency of CYP2A6 gene deletion and its relation to risk of lung and esophageal cancer in the Chinese population. Int J Cancer 95: 96–101.

    Google Scholar 

  11. Smith TJ, Liao A, Wang LD, et al.(1998) Characterization of xenobiotic-metabolizing enzymes and nitrosamine metabolism in the human esophagus. Carcinogenesis 19: 667–672.

    Google Scholar 

  12. Roth MJ, Dawsey SM, Wang G, et al.(2000) Association between GSTM1*0 and squamous dysplasia of the esophagus in the high risk region of Linxian, China. Cancer Lett 156: 73–81.

    Google Scholar 

  13. Nebert DW, Ingelman-Sundberg M, Daly AK (1999) Genetic epidemiology of environmental toxicity and cancer susceptibility: human allelic polymorphisms in drug-metabolizing enzyme genes, their functional importance, and nomenclature issues. Drug Metab Rev 31: 467–487.

    Google Scholar 

  14. Roth MJ, Guo-Qing W, Lewin KJ, et al.(1998) Histopathologic changes seen in esophagectomy specimens from the high-risk region of Linxian, China:potential clues to an etiologic exposure? Hum Pathol 29&: 1294–12

    Google Scholar 

  15. Roth MJ, Strickland KL, Wang GQ, Rothman N, Greenberg A, Dawsey SM (1998) High levels of carcinogenic polycyclic aromatic hydrocarbons present within food from Linxian, China may contribute to that region 's high incidence of oesophageal cancer. Eur J Cancer 34&: 757–7

    Google Scholar 

  16. Roth MJ, Qiao Y-L, Rothman N, et al.(2001) High urine 1-hydroxypyrene glucuronide concentrations in Linxian, China, an area of high risk for squamous oesophageal cancer. Biomarkers 6: 381–386.

    Google Scholar 

  17. Wornat MJ, Ledesma EB, Sandrowitz AK, et al.(2001) Polycyclic aromatic hydrocarbons identi ed in soot extracts from domestic coal-burning stoves of Henan Province, China. Environ Sci Technol 35: 1943–1952.

    Google Scholar 

  18. Smith G, Stanley LA, Sim E, Strange RC, Wolf CR (1995) Metabolic polymorphisms and cancer susceptibility. Cancer Surv 25: 27–65.

    Google Scholar 

  19. Bartsch H, Nair U, Risch A, Rojas M, Wikman H, Alexandrov K (2000) Genetic polymorphism of CYP genes, alone or in combination, as a risk modi er of tobacco-related cancers. Cancer Epidemiol Biomarkers Prev 9: 3–28.

    Google Scholar 

  20. Landi S (2000) Mammalian class theta GST and differential susceptibility to carcinogens:a review. Mutat Res 463: 247–283.

    Google Scholar 

  21. Li B, Taylor PR, Li JY, et al.(1993) Linxian nutrition intervention trials.Design, methods, participant characteristics, and compli-ance. Ann Epidemiol 3: 577–585.

    Google Scholar 

  22. Liu SF, Shen Q, Dawsey SM, et al.(1994) Esophageal balloon cytology and subsequent risk of esophageal and gastric-cardia cancer in a high-risk Chinese population. Int J Cancer 57: 775–780.

    Google Scholar 

  23. Dawsey SM, Yu Y, Taylor PR, et al.(1994) Esophageal cytology and subsequent risk of esophageal cancer:a prospective follow-up study from Linxian, China. Acta cytol 38: 183–192.

    Google Scholar 

  24. Li JY, Taylor PR, Li B, Dawsey S, et al.(1993) Nutrition Intervention Trials in Linxian, China:Multiple vitamin/mineral supplementation, cancer incidence, and disease-speci c mortality among adults with esophageal dysplasia. J Natl Cancer Inst 85: 1492–1498.

    Google Scholar 

  25. Blot WJ, Li JY, Taylor PR, et al.(1993) Nutrition intervention trials in Linxian, China:supplementation with speci c vitamin/ mineral combinations, cancer incidence, and disease-speci c mortality in the general population. J Natl Cancer Inst 85: 1483–1492.

    Google Scholar 

  26. Prentice RLA (1986) A case cohort design for epidemiologic cohort studies and disease prevention trials. Biometrika 73: 1–11.

    Google Scholar 

  27. Self SG, Prentice RLA (1988) Asymptotic distribution theory and ef ciency results for case-cohort studies. Annals of Statistics 16: 64–81.

    Google Scholar 

  28. Mark SD, Katki H (2001) Influence function based variance estimation and missing data issues in case-cohort studies. Lifetime Data Analysis 7: 331–334.

    Google Scholar 

  29. Hu X, Xia H, Srivastava SK, et al.(1997) Activity of four allelic forms of glutathione S-transferase hGSTP1–1 for diol epoxides of polycyclic aromatic hydrocarbons. Biochem Biophys Res Commun 238: 397–402.

    Google Scholar 

  30. Eaton DL, Bammler TK (1999) Concise review of the glutathione S-transferases and their signi cance to toxicology. Toxicol Sci 49: 156–164.

    Google Scholar 

  31. Nebert DW, McKinnon RA, Puga A (1996) Human drug-metabolizing enzyme polymorphisms:effects on risk of toxicity and cancer. DNA Cell Biol 15: 273–280.

    Google Scholar 

  32. Nimura Y, Yokoyama S, Fujimori M, et al.(1997) Genotyping of the CYP1A1 and GSTM1 genes in esophageal carcinoma patients with special reference to smoking. Cancer 80: 852–857.

    Google Scholar 

  33. Bartsch H (1996) DNA adducts in human carcinogenesis: etiological relevance and structure-activity relationship. Mutat Res 340: 67–79.

    Google Scholar 

  34. Hong YC, Leem JH, Park HS, et al.(1999) Variations in urinary 1-hydroxypyrene glucuronide in relation to smoking and the modi cation effects of GSTM1 and GSTT1. Toxicol Lett 108: 217–223.

    Google Scholar 

  35. Popp W, Vahrenholz C, Schell C, et al.(1997) DNA single strand breakage, DNA adducts, and sister chromatid exchange in lymphocytes and phenanthrene and pyrene metabolites in urine of coke oven workers. Occup Environ Med 54: 176–183.

    Google Scholar 

  36. Chernogolov A, Behlke J, Schunck WH, Roots I, Schwarz D (2003) Human CYP1A1 allelic variants:baculovirus expression and puri cation, hydrodynamic, spectral, and catalytical proper-ties and their potency in the formation of all-trans-retinoic acid. Protein Expr Purif 28&: 259–2

    Google Scholar 

  37. Schwarz D, Kisselev P, Honeck H, Cascorbi I, Schunck WH, Roots I (2001) Co-expression of human cytochrome P4501A1 (CYP1A1)variants and human NADPH-cytochrome P450 reductase in the baculovirus/insect cell system. Xenobiotica 31: 345–356.

    Google Scholar 

  38. Schwarz D, Kisselev P, Cascorbi I, Schunck WH, Roots I (2001) Differential metabolism of benzo [a ]pyrene and benzo [a ]pyrene-7, 8-dihydrodiol by human CYP1A1 variants. Carcinogenesis 22: 453–459.

    Google Scholar 

  39. Pavanello S, Clonfero E (2000) Biological indicators of genotoxic risk and metabolic polymorphisms. Mutat Res 463: 285–308.

    Google Scholar 

  40. Tan W, Song N, Wang GQ, et al.(2000) Impact of genetic polymorphisms in cytochrome P450 2E1 and glutathione S-transferases M1, T1, and P1 on susceptibility to esophageal cancer among high-risk individuals in China. Cancer Epidemiol Biomarkers Prev 9: 551–556.

    Google Scholar 

  41. Dawsey SM, Lewin KJ, Wang, GQ, et al.(1994) Squamous esophageal histology and subsequent risk of squamous cell carcinoma of the esophagus.A prospective follow-up study from Linxian, China. Cancer 74: 1686–1692.

    Google Scholar 

  42. van Lieshout EM, Posner GH, Woodard BT, Peters WH (1998) Effects of the sulforaphane analog compound 30, indole-3-carbinol, D-limonene or relafen on glutathione S-transferases and glutathione peroxidase of the rat digestive tract. Biochim Biophys Acta 1379: 325–336.

    Google Scholar 

  43. van Lieshout EM, Tiemessen DM, Peters WH, Jansen JB (1997) Effects of nonsteroidal anti-in.ammatory drugs on glutathione S-transferases of the rat digestive tract. Carcinogenesis 18: 485–490.

    Google Scholar 

  44. Spitz MR, Duphorne CM, Detry MA, et al.(2000) Dietary intake of isothiocyanates:evidence of a joint e.ect with glutathione S-transferase polymorphisms in lung cancer risk. Cancer Epidemiol Biomarkers Prev 9: 1017–1020.

    Google Scholar 

  45. Zhang Y, Talalay P (1998) Mechanism of differential potencies of isothiocyanates as inducers of anticarcinogenic Phase 2 enzymes. Cancer Res 58: 4632–4639.

    Google Scholar 

  46. Lan Q, He X, Costa DJ, et al.(2000) Indoor coal combustion emissions, GSTM1 and GSTT1 genotypes, and lung cancer risk:a case-control study in Xuan Wei, China. Cancer Epidemiol Biomarkers Prev 9: 605–608.

    Google Scholar 

Download references

Author information

Authors and Affiliations

  1. NIH, NCI, CCR, CPSB, Cancer Prevention Studies Branch, 6116 Executive Boulevard Suite 705, Bethesda, MD, 20892-8314, USA

    Mark J. Roth, Christian C. Abnet, Laura Lee Johnson, Steven D. Mark, Philip R. Taylor & Sanford M. Dawsey

  2. Cancer Institute, Chinese Academy of Medical Science, Beijing, 100021, P.R. China

    Zhi Wei Dong & You-Lin Qiao

  3. Department of Epidemiology, Cancer Institute Chinese Academy of Medical Sciences, P.O. Box 2252, Beijing, 100021, P.R. China

    You-Lin Qiao

Authors
  1. Mark J. Roth
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Christian C. Abnet
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Laura Lee Johnson
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Steven D. Mark
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Zhi Wei Dong
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Philip R. Taylor
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Sanford M. Dawsey
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. You-Lin Qiao
    View author publications

    You can also search for this author in PubMed Google Scholar

Rights and permissions

Reprints and permissions

About this article

Cite this article

Roth, M.J., Abnet, C.C., Johnson, L.L. et al. Polymorphic variation of CYP1A1 is associated with the risk of gastric cardia cancer: a prospective case–cohort study of cytochrome P-450 1A1 and GST enzymes. Cancer Causes Control 15, 1077–1083 (2004). https://doi.org/10.1007/s10552-004-2233-3

Download citation

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10552-004-2233-3

Search

Navigation