European Journal of Epidemiology

, Volume 25, Issue 7, pp 491–500 | Cite as

CYP1A2 polymorphisms, occupational and environmental exposures and risk of bladder cancer

  • Sofia Pavanello
  • Giuseppe Mastrangelo
  • Donatella Placidi
  • Marcello Campagna
  • Alessandra Pulliero
  • Angela Carta
  • Cecilia Arici
  • Stefano Porru
CANCER
First Online:
Received:
Accepted:

Abstract

Cytochrome P4501A2 (CYP1A2) is a key enzyme for activation of bladder carcinogens. Polymorphisms in the 5′-noncoding promoter region of CYP1A2 gene [mainly −2467T/delT(rs35694136) and −163C/A(rs762551)], are crucial in modifying CYP1A2 activity in smokers. Within the framework of a hospital-based case/control study, we investigated the relationship between CYP1A2 polymorphisms, occupational/environmental exposures and bladder cancer (BC) risk. The study population included 185 BC cases and 180 non-cancer controls, all Caucasian males. Data were collected on lifetime smoking, coffee drinking, dietary habits and lifetime occupation, with particular reference to exposure to aromatic amines (AAs) and polycyclic aromatic hydrocarbons (PAHs). A case-only design was applied to study the interaction between CYP1A2 −2467T/delT (or −163C/A) and occupational and environmental factors. Multiple logistic regression showed a significantly increased risk among heavy smokers (≥50 packyears; OR 5.6, 95% CI: 2.5–12.5) and heavy coffee drinkers (>5 cups/day; OR 3.1, 95% CI: 1.2–7.9). Exposure to AAs showed a significant trend of BC risk with increasing cumulative exposure (CE) (P = 0.04), with heavy smoking as possible confounder. A decreased risk was noted for large leaf vegetable consumption, with significant trend from <1/month to >3 times/week (P = 0.008). The case-only analysis showed an interaction between −2467T/delT and tobacco smoking >25 packyears (P = 0.04); no interaction was detected between such polymorphisms and coffee consumption, dietary habits and occupational exposure to AAs. No effects were shown with −163C/A genotype as well as no overall effect of CYP1A2 by itself on BC risk. This is the first study suggesting that CYP1A2 −2467T/delT modifies the effect of cigarette smoking on BC risk.

Keywords

Bladder cancer CYP1A2 genotype Occupational/environmental exposures 
This is a preview of subscription content, log in to check access.

Notes

Acknowledgments

Italian Association for Research on Cancer (AIRC) 2008.

References

  1. 1.
    Landi MT, Sinha R, Lang NP, Kadlubar FF. Chapter 16. Human cytochrome P4501A2. In: Vineis P, Malats N, Lang M, d’Errico A, Caporaso N, Cuzick J, Moffetta P, editors. Metabolic polymorphisms and susceptibility to cancer. Lyon: IARC Scientific Publications, IARC; 1999. 148, p. 173–195.Google Scholar
  2. 2.
    Bartsch H, Nair U, Risch A, Rojas M, Wikman H, Alexandrov K. Genetic polymorphism of CYP genes, alone or in combination, as a risk modifier of tobacco-related cancers. Cancer Epidemiol Biomarkers Prev. 2000;9:3–28.PubMedGoogle Scholar
  3. 3.
    Butler MA, Lang NP, Young JF, Caporaso NE, Vineis P, Hayes RB, Teitel CH, Massengill JP, Lawsen MF, Kadlubar FF. Determination of CYP1A2 and NAT2 phenotypes in human populations by analysis of caffeine urinary metabolites. Pharmacogenetics. 1992;2:116–27.CrossRefPubMedGoogle Scholar
  4. 4.
    Pavanello S, Simioli P, Lupi S, Gregorio P, Clonfero E. Exposure levels and cytochrome P450 1A2 activity, but not N-acetyltransferase, glutathione S-transferase (GST) M1 and T1, influence urinary mutagen excretion in smokers. Cancer Epidemiol Biomarkers Prev. 2002;11:998–1003.PubMedGoogle Scholar
  5. 5.
    Sesardic D, Boobis AR, Edwards RJ, Davies DS. A form of cytochrome P450 in man, orthologous to form d in the rat, catalyses the odeethylation of phenacetin and is inducible by cigarette smoking. Br J Clin Pharmacol. 1988;26:363–72.PubMedGoogle Scholar
  6. 6.
    Chung WG, Kang JH, Park CS, Cho MH, Cha YN. Effect of age and smoking on in vivo CYP1A2, flavin-containing monooxygenase, and xanthine oxidase activities in Koreans: determination by caffeine metabolism. Clin Pharmacol Ther. 2000;67:258–66.CrossRefPubMedGoogle Scholar
  7. 7.
    Nordmark A, Lundgren S, Cnattingius S, Rane A. Dietary caffeine as a probe agent for assessment of cytochrome P4501A2 activity in random urine samples. Br J Clin Pharmacol. 1999;47:397–402.CrossRefPubMedGoogle Scholar
  8. 8.
    Pavanello S, Pulliero A, Lupi S, Gregorio P, Clonfero E. Influence of the genetic polymorphism in the 5’-noncoding region of the CYP1A2 gene on CYP1A2 phenotype and urinary mutagenicity in smokers. Mutat Res. 2005;587:59–66.PubMedGoogle Scholar
  9. 9.
    Pavanello S, B’chir F, Pulliero A, Saguem S, Ben Fraj R, El Aziz Hayouni A, Clonfero E, Mastrangelo G. Interaction between CYP1A2-T2467DELT polymorphism and smoking in adenocarcinoma and squamous cell carcinoma of the lung. Lung Cancer. 2007;57:266–72.CrossRefPubMedGoogle Scholar
  10. 10.
    International Agency for Research on Cancer. World cancer report 2008. In: Boyle P, Levin B, editors. WHO Press, Geneva; 2008.Google Scholar
  11. 11.
    AIRT Working Group. Italian cancer figures—report 2006: 1. Incidence, mortality and estimates. Epidemiol Prev 2006; 30: 8–101.Google Scholar
  12. 12.
    Pelucchi C, Bosetti C, Negri E, Malvezzi M, La Vecchia C. Mechanisms of disease: the epidemiology of bladder cancer. Nat Clin Pract Urol. 2006;3:327–40.CrossRefPubMedGoogle Scholar
  13. 13.
    Kogevinas M, Trichopoulos D. Urinary bladder cancer. In: Adami HO, Hunter D, Trichopoulos D, editors. Textbook of cancer epidemiology. New York: Oxford University Press; 2002. p. 446–66.Google Scholar
  14. 14.
    Kamat ALJ, Gu J, Chen M, Dinney CP, Forman MR, Wu X. Dietary intake of vegetables and fruit and the modification effects of GSTM1 and NAT2 genotypes on bladder cancer risk. Cancer Epidemiol Biomarkers Prev. 2009;18:2090–7.CrossRefPubMedGoogle Scholar
  15. 15.
    Kellen E, Zeegers M, Paulussen A, Van Dongen M, Buntinx F. Fruit consumption reduces the effect of smoking on bladder cancer risk. The Belgian case control study on bladder cancer. Int J Cancer. 2006;118:2572–8.CrossRefPubMedGoogle Scholar
  16. 16.
    García-Closas R, García-Closas M, Kogevinas M, Malats N, Silverman D, Serra C, Tardón A, Carrato A, Castaño-Vinyals G, Dosemeci M, Moore L, Rothman N, et al. Food, nutrient and heterocyclic amine intake and the risk of bladder cancer. Eur J Cancer. 2007;43:1731–40.CrossRefPubMedGoogle Scholar
  17. 17.
    Riboli E, Norat T. Epidemiologic evidence of the protective effect of fruit and vegetables on cancer risk. Am J Clin Nutr. 2003;78:559–69.Google Scholar
  18. 18.
    Büchner FL, Bueno-de-Mesquita HB, Ros MM, Kampman E, Egevad L, Overvad K, Raaschou-Nielsn O, Tiønneland A, Roswall N, Clavel-Chapelon F, Boutron-Ruault MC, Touillaud M, Chang-Claude J, Kaaks R, Boeing H, Weikert S, Trichopoulou A, Lagiou P, Trichopoulos D, Palli D, Sieri S, Vineis P, Tumino R, Panico S, Vrieling A, Peeters PH, van Gils CH, Luund E, Gram IT, Engeset D, Martinez C, Gonzalez CA, Larrañaga N, Ardanaz E, Navarro C, Rodriguez L, Manjer J, Ehrnström RA, Hallmans G, Ljungberg B, Allen NE, Roddam AVV, Bingham S, Khaw KT, Silmani N, Boffetta P, Jenab M, Mouw T, Michaud DS, Kiemeney LA, Riboli E. Consumption of vegetables and fruit and the risk of bladder cancer in the European prospective investigation into cancer and nutrition. Int J Cancer. 2009;125:2643–51.CrossRefPubMedGoogle Scholar
  19. 19.
    Larsson SC, Andersson SO, Johansson JE, Wolk A. Fruit and vegetable consumption and risk of bladder cancer: a prospective cohort study. Cancer Epidemiol Biomarkers Prev. 2008;17:2519–22.CrossRefPubMedGoogle Scholar
  20. 20.
    International Agency for Research on Cancer (IARC). Coffee, tea, mate, methylxanthines and methylglyoxal. In: IARC Monographs on the evaluation of carcinogenic risks to humans. Lyon; 1991.Google Scholar
  21. 21.
    Covolo L, Placidi D, Gelatti U, Carta A, Scotto Di Carlo A, Lodetti P, Piccichè A, Orizio G, Campagna M, Arici C, Porru S. Bladder cancer, GSTs, NAT1, NAT2, SULT1A1, XRCC1, XRCC3, XPD genetic polymorphisms and coffee consumption: a case-control study. Eur J Epidemiol. 2008;23:355–62.CrossRefPubMedGoogle Scholar
  22. 22.
    Sala M, Cordier S, Chang-Claude J, Donato F, Escolar-Pujolar A, Fernandez F, González CA, Greiser E, Jöckel KH, Lynge E, Mannetje A, Pohlabeln H, et al. Coffee consumption and bladder cancer in nonsmokers: a pooled analysis of case–control studies in European countries. Cancer Causes Control. 2000;11:925–31.CrossRefPubMedGoogle Scholar
  23. 23.
    Pelucchi C, La Vecchia C. Alcohol, coffee, and bladder cancer risk: a review of epidemiological studies. Eur J Cancer Prev. 2009;18:62–8.CrossRefPubMedGoogle Scholar
  24. 24.
    Villanueva CM, Silverman DT, Murta-Nascimento C, Malats N, Garcia-Closas M, Castro F, Tardon A, Garcia-Closas R, Serra C, Carrato A, Rothman N, Real FX, et al. Coffee consumption, genetic susceptibility and bladder cancer risk. Cancer Causes Control. 2009;20:121–7.CrossRefPubMedGoogle Scholar
  25. 25.
    Woolcott CG, King WD, Marrett LD. Coffee and tea consumption and cancers of the bladder, colon and rectum. Eur J Cancer Prev. 2002;11:137–45.CrossRefPubMedGoogle Scholar
  26. 26.
    Zeegers MP, Tan FE, Goldbohm RA, van den Brandt PA. Are coffee and tea consumption associated with urinary tract cancer risk? A systematic review and meta-analysis. Int J Epidemiol. 2001;30:353–62.CrossRefPubMedGoogle Scholar
  27. 27.
    Hung RJ, Boffetta P, Brennan P, Malaveille C, Hautefeuille A, Donato F, Gelatti U, Spaliviero M, Placidi D, Carta A, Scotto di Carlo A, Porru S. GST, NAT, SULT1A1, CYP1B1 genetic polymorphisms, interactions with environmental exposures and bladder cancer risk in a high-risk population. Int J Cancer. 2004;110:598–604.CrossRefPubMedGoogle Scholar
  28. 28.
    Shen M, Hung RJ, Brennan P, Malaveille C, Donato F, Placidi D, Carta A, Hautefeuille A, Boffetta P, Porru S. Polymorphisms of the DNA repair genes XRCC1, XRCC3, XPD, interaction with environmental exposures, and bladder cancer risk in a case–control study in northern Italy. Cancer Epidemiol Biomarkers Prev. 2003;12:1234–40.PubMedGoogle Scholar
  29. 29.
    Hung RJ, Boffetta P, Brennan P, Malaveille C, Gelatti U, Placidi D, Carta A, Hautefeuille A, Porru S. Genetic polymorphisms of MPO, COMT, MnSOD, NQO1, interactions with environmental exposures and bladder cancer risk. Carcinogenesis. 2004;25:973–8.CrossRefPubMedGoogle Scholar
  30. 30.
    Schlesselman JJ. Case-control studies: design, conduct, analysis. USA: Oxford University Press; 1982. p. 145.Google Scholar
  31. 31.
    Cohen J, Cohen P, West SG, Aiken LS. Applied multiple regression/correlation analysis for the behavioral sciences. 3rd ed. Mahwah, NJ: Lawrence Earlbaum Associates; 2003.Google Scholar
  32. 32.
    Yang Q, Khoury MJ, Flanders WD. Sample size requirements in case-only designs to detect gene-environment interaction. Am J Epidemiol. 1997;146:713–20.PubMedGoogle Scholar
  33. 33.
    Porru S, Placidi D, Carta A, Gelatti U, Ribero ML, Tagger A, Boffetta P, Donato F. Primary liver cancer and occupation in men: a case–control study in high-incidence area in Northern Italy. Int J Cancer. 2001;94:878–83.CrossRefPubMedGoogle Scholar
  34. 34.
    Altayli E, Gunes S, Yilmaz AF, Goktas S, Bek Y. CYP1A2, CYP2D6, GSTM1, GSTP1, and GSTT1 gene polymorphisms in patients with bladder cancer in a Turkish population. Int Urol Nephrol. 2009;41:259–66.CrossRefPubMedGoogle Scholar
  35. 35.
    Figueroa JD, Malats N, García-Closas M, Real FX, Silverman D, Kogevinas M, Chanock S, Welch R, Dosemeci M, Lan Q, Tardón A, Serra C, et al. Bladder cancer risk and genetic variation in AKR1C3 and other metabolizing genes. Carcinogenesis. 2008;29:1955–62.CrossRefPubMedGoogle Scholar
  36. 36.
    Quattrochi LC, Vu T, Tukey RH. The human CYP1A2 gene and induction by 3-methylcholanthrene. A region of DNA that supports AH-receptor binding and promoter-specific induction. J Biol Chem. 1994;269:6949–54.PubMedGoogle Scholar
  37. 37.
    Sogawa K, Fujii-Kuriyama Y. Ah receptor, a novel ligand-activated transcription factor. J Biochem. 1997;122:1075–9.PubMedGoogle Scholar
  38. 38.
    Hankinson O. The aryl hydrocarbon receptor complex. Annu Rev Pharmacol Toxicol. 1995;35:307–40.CrossRefPubMedGoogle Scholar
  39. 39.
    Hayashi S, Watanabe J, Kawajiri K. Genetic polymorphisms in the 5’-flanking region change transcriptional regulation of the human cytochrome P450IIE1 gene. J Biochem. 1991;110:559–65.PubMedGoogle Scholar
  40. 40.
    International Agency for Research on Cancer (IARC). Working Group on the Evaluation of Carcinogenic Risks to Humans. Tobacco smoke and involuntary smoking. In: Lyon: IARC Scientific Publications; 2004; 83: 1–1438.Google Scholar
  41. 41.
    Bartsch H, Caporaso N, Coda M, Kadlubar F, Malaveille C, Skipper P, Talaska G, Tannenbaum SR, Vineis P. Carcinogen hemoglobin adducts, urinary mutagenicity, and metabolic phenotype in active and passive cigarette smokers. J Natl Cancer Inst. 1990;82:1826–31.CrossRefPubMedGoogle Scholar
  42. 42.
    Vineis P, Talaska G, Malaveille C, Bartsch H, Martone T, Sithisarankul P, Strickland P. DNA adducts in urothelial cells: relationship with biomarkers of exposure to arylamines and polycyclic aromatic hydrocarbons from tobacco smoke. Int J Cancer. 1996;65:314–6.CrossRefPubMedGoogle Scholar
  43. 43.
    Hecht SS. Cigarette smoking: cancer risks, carcinogens, and mechanisms. Langenbecks Arch Surg. 2006;391:603–13.CrossRefPubMedGoogle Scholar
  44. 44.
    Talaska G, Al-Juburi AZSS, Kadlubar FF. Smoking related carcinogen–DNA adducts in biopsy samples of human urinary bladder: identification of N-(deoxyguanosin-8-yl)-4-aminobiphenyl as a major adduct. Proc Natl Acad Sci USA. 1991;88:5350–4.CrossRefPubMedGoogle Scholar
  45. 45.
    Curigliano G, Zhang YJ, Wang LY, Flamini G, Alcini A, Ratto C, Giustacchini M, Alcini E, Cittadini A, Santella RM. Immunohistochemical quantitation of 4-aminobiphenyl–DNA adducts and p53 nuclear overexpression in T1 bladder cancer of smokers and nonsmokers. Carcinogenesis. 1996;17:911–6.CrossRefPubMedGoogle Scholar
  46. 46.
    Feng Z, Hu W, Rom WN, Beland FA, Tang MS. 4-aminobiphenyl is a major etiological agent of human bladder cancer: evidence from its DNA binding spectrum in human p53 gene. Carcinogenesis. 2002;23:1721–7.CrossRefPubMedGoogle Scholar
  47. 47.
    Saletta F, Matullo G, Manuguerra M, Arena S, Bardelli A, Vineis P. Exposure to the tobacco smoke constituent 4-Aminobiphenyl induces chromosomal instability in human cancer cells. Cancer Res. 2007;67:7088–94.CrossRefPubMedGoogle Scholar
  48. 48.
    Butler MA, Guengerich FP, Kadlubar FF. Metabolic oxidation of the carcinogens 4-aminobiphenyl and 4, 4′-methylenebis(2-chloroaniline) by human hepatic microsomes and by purified rat hepatic cytochrome P-450 monooxygenases. Cancer Res. 1989;49:25–31.PubMedGoogle Scholar
  49. 49.
    Kadlubar FF, Miller JA, Miller EC. Hepatic microsomal N-glucuronidation and nucleic acid binding of N-hydroxy arylamines in relation to urinary bladder carcinogenesis. Cancer Res. 1977;37:805–14.PubMedGoogle Scholar
  50. 50.
    Kadlubar FF. Carcinogenic aromatic amine metabolism and DNA adduct detection in human. In: Emster L, editor. Xenobiotics and cancer. London: Taylor & Francis, Ltd.; 1991. p. 329–38.Google Scholar
  51. 51.
    Bartsch H, Malaveille C, Friesen M, Kadlubar FF, Vineis P. Black (air-cured) and blond (flue-cured) tobacco cancer risk. IV. Molecular dosimetrystudies implicates aromatic amines as bladder carcinogens. Eur J Cancer. 1993;29:1199–207.CrossRefGoogle Scholar
  52. 52.
    Frederickson SM, Messing EM, Renikoff CA, Swaminathan S. Relationship between in vivo acetylator phenotypes and cytosolic N-acetyltransferase and O-acetyltransferase activities in human uroepithelial cells. Cancer Epidemiol Biomark Prev. 1994;3:25–32.Google Scholar
  53. 53.
    Sinués B, Sáenz MA, Lanuza J, Bernal ML, Fanlo A, Juste JL, Mayayo E. Five caffeine metabolite ratios to measure tobacco-induced CYP1A2 activity and their relationships with urinary mutagenicity and urine flow. Cancer Epidemiol Biomarkers Prev. 1999;8:159–66.PubMedGoogle Scholar
  54. 54.
    Murray S, Lake BG, Gray S, Edwards AJ, Springall C, Bowey EA, Williamson G, Boobis AR, Gooderham NJ. Effect of cruciferous vegetable consumption on heterocyclic aromatic amine metabolism in man. Carcinogenesis. 2001;22:1413–20.CrossRefPubMedGoogle Scholar
  55. 55.
    Pavanello S, Simioli P, Mastrangelo G, Lupi S, Gabbani G, Gregorio P, Clonfero E. Role of metabolic polymorphisms NAT2 and CYP1A2 on urinary mutagenicity after a pan-fried hamburger meal. Food Chem Toxicol. 2002;40:1139–44.CrossRefPubMedGoogle Scholar
  56. 56.
    Landi MT, Zocchetti C, Bernucci I, Kadlubar FF, Tannenbaum S, Skipper P, Bartsch H, Malaveille C, Shields P, Caporaso NE, Vineis P. Cytochrome P4501A2: enzyme induction and genetic control in determining 4-aminobiphenyl-hemoglobin adduct levels. Cancer Epidemiol Biomarkers Prev. 1996;5:693–8.PubMedGoogle Scholar
  57. 57.
    Kadlubar FF, Dooley KL, Teitel CH, Roberts DW, Benson RW, Butler MA, Bailey JR, Young JF, Skipper PW, Tannenbaum SR. The frequency of urination and its effects on metabolism pharmacokinetics, blood hemoglobin adduct formation, and liver and urinary bladder DNA adduct levels in Beagle dogs administered the carcinogen, 4-aminobiphenyl. Cancer Res. 1991;51:4371–7.PubMedGoogle Scholar
  58. 58.
    Chen M, Kamat AM, Huang M, Grossman HB, Dinney CP, Lerner SP, Wu X, Gu J. High-order interactions among genetic polymorphisms in nucleotide excision repair pathway genes and smoking in modulating bladder cancer risk. Carcinogenesis. 2007;28:2160–5.CrossRefPubMedGoogle Scholar
  59. 59.
    Manuguerra M, Matullo G, Veglia F, Autrup H, Dunning AM, Garte S, Gormally E, Malaveille C, Guarrera S, Polidoro S, Saletta F, Peluso M, et al. Multi-factor dimensionality reduction applied to a large prospective investigation on gene-gene and gene-environment interactions. Carcinogenesis. 2007;28:414–22.CrossRefPubMedGoogle Scholar
  60. 60.
    Andrew AS, Nelson HH, Kelsey KT, Moore JH, Meng AC, Casella DP, Tosteson TD, Schned AR, Karagas MR. Concordance of multiple analytical approaches demonstrates a complex relationship between DNA repair gene SNPs, smoking and bladder cancer susceptibility. Carcinogenesis. 2006;27:1030–7.CrossRefPubMedGoogle Scholar

Copyright information

© Springer Science+Business Media B.V. 2010

Authors and Affiliations

  • Sofia Pavanello
    • 1
  • Giuseppe Mastrangelo
    • 1
  • Donatella Placidi
    • 2
  • Marcello Campagna
    • 2
  • Alessandra Pulliero
    • 1
  • Angela Carta
    • 2
  • Cecilia Arici
    • 2
  • Stefano Porru
    • 2
  1. 1.Occupational Health Section, Department of Environmental Medicine and Public HealthUniversity of PadovaPadovaItaly
  2. 2.Department of Experimental and Applied Medicine, Section of Occupational Medicine and Industrial HygieneUniversity of BresciaBresciaItaly

Personalised recommendations