CYP1A1, smoking and venous thromboembolism

 

 Buy Article Permissions and Reprints

Summary

Since CYP1A1 enzyme is involved in metabolism of tobacco carcinogens, the CYP1A1 gene may be of relevance to smoking-induced differences in the risks of venous thromboembolism (VTE). We conducted a case-control study to investigate genetic polymorphisms in CYP1A1 that might modify the risk of developing VTE. A total of 425 Chinese patients with VTE and 527 VTE-free control individuals, matched by age and gender, were included in this analysis. The MspI and Ile462Val polymorphisms in CYP1A1 gene were analysed using the Amplification Refractory Mutation System (ARMS) method. The Ile462Val AG variant and combined AG and GG variant was significantly associated with VTE, adjusted for age, gender, weight and contraceptives (OR=1.362, 95%CI 1.026, 1.809, p=0.033; OR=1.420, 95% CI 1.081, 1.865, p=0.012, respectively); The AG and GG combined variant was still significantly associated with VTE when adjusting further for smoking (OR=1.344, 95%CI 1.019,1.772, p=0.036) A more than two-fold increase for VTE was associated with the Ile462Val combined variant of AG+GG (OR of 2.805, 95% CI 1.250, 6.293, p=0.012) in the smokers. Genetic variations of CYP1A1 Ile462Val contribute to susceptibility to smoking-induced VTE in the Chinese populations. A two-fold increase in the risk in the smokers in the patients who carry CYP1A1 Ile462Val variant alleles has demonstrated the importance of gene-environment interactions in the development of this disease.

^* These authors contributed equally to this work.

• References

• 1 Peterson D, Harward S, Lawson JH. Anticoagulation strategies for venous thromboembolism. Perspect Vasc Surg Endovasc Ther 2009; 21: 123-132.
  PubMedGoogle Scholar
• 2 Gohil R, Peck G, Sharma P. The genetics of venous thromboembolism: A meta-analysis involving120,000 cases and 180,000 controls. Thromb Haemost 2009; 102: 360-370.
  Article in Thieme ConnectPubMedGoogle Scholar
• 3 Hansson PO, Eriksson H, Welin L. et al. Smoking and Abdominal Obesity. Arch Intern Med 1999; 159: 1886-1890.
  CrossrefPubMedGoogle Scholar
• 4 Larsen TB, Sørensen HT, Gislum M. et al. Maternal smoking, obesity, and risk of venous thromboembolism during pregnancy and the puerperium: a population-based nested case-control study. Thromb Res 2007; 120: 505-509.
  CrossrefPubMedGoogle Scholar
• 5 Severinsen MT, Kristensen SR, Johnsen SP. et al. Smoking and venous thromboembolism: a Danish follow-up study. J Thromb Haemost 2009; 7: 1297-1303.
  CrossrefPubMedGoogle Scholar
• 6 Androustsopoulos VP, Tsatsakis AM, Spandidos DA. Cytochrome P450 CYP1A1: wider roles in cancer progression and prevention. BMC cancer 2009; 9: 187.
  CrossrefPubMedGoogle Scholar
• 7 Zhou SF, Liu JP, Chowbay B. Polymorphism of human cytochrome P450 enzymes and its clinical impact. Drug Metabolism Reviews 2009; 41: 89-295.
  CrossrefPubMedGoogle Scholar
• 8 Božina N, Bradamante V, Lovric M. Genetic polymorphism of metabolic enzymes P450 (CYP) as a susceptibility factor for drug response, toxicity, and cancer risk. Arh Hig Rada Toksikol 2009; 60: 217-242.
  CrossrefPubMedGoogle Scholar
• 9 Shi X, Zhou S, Wang Z. et al. CYP1A1 and GSTM1 polymorphisms and lung cancer risk in Chinese populations: A meta-analysis. Lung Cancer 2008; 59: 155-163.
  CrossrefPubMedGoogle Scholar
• 10 Wright CM, Larsen JE, Colosimo ML. et al. Genetic association study of CYP1A1 polymorphisms identifies risk haplotypes in nonsmall cell lung cancer. Eur Respir J 2010; 35: 152-159.
  CrossrefPubMedGoogle Scholar
• 11 Shaffi SM, Shah MA, Bhat IA. et al. CYP1A1 polymorphisms and risk of lung cancer in the ethnic Kashmiri population. Asian Pac J Cancer Prev. 2009; 10: 651-656.
  PubMedGoogle Scholar
• 12 Syamala VS, Syamala V, Sheeja VR. et al. Possible risk modification by polymorphisms of estrogen metabolizing genes in familial breast cancer susceptibility in an Indian population. Cancer Invest 2010; 28: 304-311.
  CrossrefPubMedGoogle Scholar
• 13 Singh AP, Shah PP, Ruwali M. et al. Polymorphism in cytochrome P4501A1 is significantly associated with head and neck cancer risk. Cancer Invest 2009; 27: 869-876.
  CrossrefPubMedGoogle Scholar
• 14 Tai J, Yang M, Ni X. et al. Genetic polymorphisms in cytochrome P450 genes are associated with an increased risk of squamous cell carcinoma of the larynx and hypopharynx in a Chinese population. Cancer Genet Cytogenet 2010; 196: 76-82.
  CrossrefPubMedGoogle Scholar
• 15 Luo X, Xu K. A solid phase method for extracting DNA from whole blood. Chin J Clin Lab Sci 2004; 22: 123-125.
  PubMedGoogle Scholar
• 16 Zhu J, Zhang W, Li Y. et al. ARMS test for diagnosis of CYP2C9 and VKORC1 mutation in patients with pulmonary embolism in Han Chinese. Pharmacogenomics 2010; 11: 113-119.
  CrossrefPubMedGoogle Scholar
• 17 Ye S, Dhillon S, Ke X. et al. An efficient procedure for genotyping single nucleotide polymorphisms. Nucleic Acids Res 2001; 29: E88-8.
  CrossrefPubMedGoogle Scholar
• 18 Iliakis G, Wang Y, Guan J. et al. DNA damage checkpoint control in cells exposed to ionizing radiation. Oncogen 2003; 22: 5834-5847.
  CrossrefPubMedGoogle Scholar
• 19 Kastan MB, Bartek J. Cell-cycle checkpoints and cancer. Nature 2004; 432: 316-323.
  CrossrefPubMedGoogle Scholar
• 20 Rich T, Allen RL, Wyllie AH. Defying death after DNA damage. Nature 2000; 407: 777-783.
  CrossrefPubMedGoogle Scholar
• 21 Tampio M, Loikkanen J, Myllynen P. et al. Benzo[a]pyrene increases phosphorylation of p53 at serine 392 in relation to p53 induction and cell death in MCF-7 cells. Toxicol Lett 2008; 178: 152-159.
  CrossrefPubMedGoogle Scholar
• 22 Lolhaug A, Øvrebø S, Mollerup S. et al. Role of cell signaling in B[a]P-induced apoptosis: characterization of unspecific effect of cell signaling inhibitors and apoptotic effects of B[a]P metabolites. Chemico-Biological Interactions 2005; 151: 110-119.
  PubMedGoogle Scholar
• 23 Solhaug A, Refsnes M, Låg M. et al. Polycyclic aromatic hydrocarbons induce both apoptotic and anti-apoptotic signals in Hepa1c1c7 cells. Carcinogenesis 2004; 25: 809-819.
  PubMedGoogle Scholar
• 24 Lu X, Shao J, Li H. et al. Early whole-genome transcriptional response induced by Benzo[a]pyrene diol epoxide in a normal human cell line. Genomics 2009; 93: 332-342.
  CrossrefPubMedGoogle Scholar
• 25 Lu KP, Hallberg LM, Tomlinson J. et al. Benzo(a)prene activates L1Md retrotransposon and inhibits DNA repair in vascular smooth muscle cells. Mutat Res 2000; 454: 35-44.
  CrossrefPubMedGoogle Scholar
• 26 Annas A, Brittebo E, Hellman B. Evaluation of benzo(a)pyrene-induced DNA damage in human endothelial cells sing alkaline single cell gel electrophoresis. Mutat Res 2000; 471: 145-155.
  CrossrefPubMedGoogle Scholar
• 27 Hakk H, Diliberto JJ, Birnbaum LS. The effect of dose on 2,3,7,8-TCDD tissue distribution, metabolism and elimination in CYP1A2 (-/-) knockout and C57BL/6N parental strains of mice. Toxicol Appl Pharmacol 2009; 241: 119-126.
  CrossrefPubMedGoogle Scholar
• 28 Lin P-H, Lin C-H, Huang C-C. et al. 2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) induces oxidative stress, DNA strand breaks, and poly (ADP-ribose) polymerase-1 activation in human breast carcinoma cell lines. Toxicol Lett 2007; 172: 146-158.
  CrossrefPubMedGoogle Scholar
• 29 Lin P-H, Lin C-H, Huang C-C. et al. 2,3,7,8-Tetrachlorodibenzo-p-dioxin modulates the induction of DNA strand breaks and poly (ADP-ribose) polymerase-1 activation by 17ß-estradiol in human breast carcinoma cells through alteration of CYP1A1 and CYP1B1 expression. Chem Res Toxicol 2008; 21: 1337-1347.
  CrossrefPubMedGoogle Scholar
• 30 Chen Z-H, Hurh Y-J, Na H-K. et al. Resveratrol inhibits TCDD-induced expression of CYP1A1 and CYP1B1 and catechol estrogen-mediated oxidative DNA damage in cultured human mammary epithelial cells. Carcinogenesis 2004; 25: 2005-2013.
  CrossrefPubMedGoogle Scholar
• 31 Sul D, Kim H-S, Cho E-K. et al. 2,3,7,8-TCDD neurotoxicity in neuroblastoma cells is caused by increased oxidative sress, intracellular calcium levels, and tau phosphorylation. Toxicology 2009; 255: 65-71.
  CrossrefPubMedGoogle Scholar
• 32 Cantrell SM, Joy-Schlezinger J, Stegeman JJ. et al. Correlation of 2,3,7,8-tetrachlorodibenzo-p-dioxin-induced apoptotic cell death in the embryonic vasculature with embryotoxicity. Toxcol Appl Pharmacol 1998; 148: 24-34.
  PubMedGoogle Scholar
• 33 Kawamura T, Yamashita I. Aryl hydrocarbon receptor is required for prevention of blood clotting and for the development of vasculature and bone in the embryos of Medaka Fish, Oryzias Iatipes. Zool Sci 2002; 19: 309-319.
  CrossrefPubMedGoogle Scholar
• 34 Teraoka H, Dong W, Hiraga T. Zebrafish as a novel experimental model for developmental toxicology. Congential Anom 2003; 43: 123-132.
  PubMedGoogle Scholar
• 35 Cantrell SM, Lutz LH, Tillitt DE. et al. Embryotoxicity of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD): The embryonic vasculature is a physiological target for TCDD-induced DNA damage and apoptotic cell death in Medaka (Orizias Iatipes). Toxicol Appl Pharmacol 1996; 141: 23-34.
  CrossrefPubMedGoogle Scholar
• 36 Korenaga T, Fukusato T, Ohta M. et al. Long-term effects of subcutaneously injected 2,3,7,8-tetrachlorodibenzo-p-dioxin on the liver of rhesus monkeys. Chemosphere 2007; 67: s399-404.
  CrossrefPubMedGoogle Scholar
• 37 Barua RS, Sy F, Srikanth S. et al. Effect of cigarette smoke exposure on clot dynamics and fibrin structure: an ex vivo investigation. Arterioscler Thromb Vasc Biol 2010; 30: 75-79.
  CrossrefPubMedGoogle Scholar
• 38 Undas A, Topór-Madry R, Tracz W. et al. Effect of cigarette smoking on plasma fibrin clot permeability and susceptibility to lysis. Thromb Haemost 2009; 102: 1289-1291.
  Article in Thieme ConnectPubMedGoogle Scholar
• 39 Kaehler J, Koeke K, Karstens M. et al. Impaaired capacity for acute endogenous fibrinolysis in smokers is restored by ascorbic acid. Free Radic Bio Med 2008; 44: 315-321.
  CrossrefPubMedGoogle Scholar
• 40 Son DS, Rosman KK. 2,3,7,8-Tetrachlorodibenzo-p -dioxin (TCDD) induces plasminogen activator inhibitor-1 through an aryl hydrocarbon receptor-mediated pathway in mouse hepatoma cell lines. Arch Toxicol 2002; 76: 404-413.
  CrossrefPubMedGoogle Scholar
• 41 Kasai A, Hiramatsu N, Hayakawa K. et al. High levels of dioxin-like potential in cigarette smoke evidenced by in vitro and in vivo biosensing. Cancer Res 2006; 66: 7143-7150.
  CrossrefPubMedGoogle Scholar
• 42 Lodovici M, Luceri C, Guglielmi F. et al. Benzo[a]pyrene Diolepoxide (BPDE)-DNA adduct levels in leukocyties of smokers in relation to polymorphism of CYP1A1, GSTM1, GSTP1, GSTT1, and mEH . Cancer Epidem Bioma 2004; 13: 1342-1348.
  PubMedGoogle Scholar
• 43 Alexandrov K, Cascorbi I, Rojas M. et al. CYP1A1 and GSTM1 genotypes affect Benzo[a]pyrene DAN adducts in smokers’ lung: comparison with aromatic / hydrophobic adduct formation. Carcinogenesis 2002; 23: 1969-1977.
  CrossrefPubMedGoogle Scholar
• 44 Rojas M, Cascorbi I, Alexandrov K. et al. Modulation of Benzo[a]pyrene diolep-oxide-DNA adduct levels in human white blood cells by CYP1A1, GSTM1 and GSTT1 polymorphism. Carcinogenesis 2000; 21: 35-41.
  CrossrefPubMedGoogle Scholar
• 45 Rojas M, Alexandrov K, Cascorbi I. et al. High Benzo[a]pyrene diol-epoxide DNA adduct levels in lung and blood cells from individuals with combined CYP1A1 MspI/MspI-GSTM1*0/*0 genotypes. Pharmacogenetics 1998; 8: 109-118.
  PubMedGoogle Scholar
• 46 Shantakumar S, Gammon MD, Eng SM. et al. Residential environmental exposures and other characteristics associated with detectable PAH-DAN adducts in peripheral mononuclear cells in a population-based sample of adult females. J Exp Anal Env Epid 2005; 15: 482-490.
  PubMedGoogle Scholar