Cancer Causes & Control

, Volume 22, Issue 1, pp 109–114 | Cite as

Intake of heterocyclic aromatic amines and the risk of prostate cancer in the EPIC-Heidelberg cohort

  • Anja Sander
  • Jakob Linseisen
  • Sabine RohrmannEmail author
Original paper



Heterocyclic amines (HCA) are positively associated with prostate cancer risk in animal models. Because of mostly inconsistent results of epidemiological studies, we examined the association between intake of HCA and prostate cancer risk.


In the EPIC-Heidelberg cohort, detailed information on diet, anthropometry, and lifestyle was assessed between 1994 and 1998. Dietary HCA intake was estimated using information on meat consumption, cooking methods, and preferred degree of browning. During 104,195 person-years of follow-up, 337 incident cases of prostate cancer (123 advanced cases) were identified among 9,578 men with valid dietary information. Multivariate Cox proportional hazards regression was used to examine the association between intake of 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP), 2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline (MeIQx), and 2-amino-3,4,8-dimethylimidazo[4,5-f]quinoxaline (DiMeIQx) and prostate cancer.


Men in the highest quartiles of PhIP, MeIQx, and DiMeIQx intake, respectively, had no increased risk of prostate cancer compared with men in the lowest quartiles (HR = 0.89, 95% CI 0.66–1.22 [PhIP]; 1.06, 0.77–1.45 [MeIQx]; 0.98, 0.72–1.34 [DiMeIQx]). There were no associations between HCA intake and advanced prostate cancer or between high consumption of strongly browned meat and prostate cancer.


Our data do not support the hypothesis that HCA intake as consumed in a regular diet is a risk factor for prostate cancer.


Heterocyclic aromatic amines Prostate cancer Cohort study 



This study was partly supported by Kurt-Eberhard-Bode-Foundation and ECNIS (Environmental Cancer Risk, Nutrition and Individual Susceptibility), a Network of Excellence of the European Commission (Contract No 513943).


  1. 1.
    Felton JS, Knize MG, Wu RW, Colvin ME, Hatch FT, Malfatti MA (2007) Mutagenic potency of food-derived heterocyclic amines. Mutat Res 616:90–94PubMedGoogle Scholar
  2. 2.
    Archer CL, Morse P, Jones RF, Shirai T, Haas GP, Wang CY (2000) Carcinogenicity of the N-hydroxy derivative of 2-amino-1-methyl-6-phenylimidazo[4, 5-b]pyridine, 2-amino-3, 8-dimethyl-imidazo[4, 5-f]quinoxaline and 3, 2’-dimethyl-4-aminobiphenyl in the rat. Cancer Lett 155:55–60CrossRefPubMedGoogle Scholar
  3. 3.
    Nakai Y, Nelson WG, De Marzo AM (2007) The dietary charred meat carcinogen 2-amino-1-methyl-6-phenylimidazo[4, 5-b]pyridine acts as both a tumor initiator and promoter in the rat ventral prostate. Cancer Res 67:1378–1384CrossRefPubMedGoogle Scholar
  4. 4.
    Sinha R, Gustafson DR, Kulldorff M, Wen WQ, Cerhan JR, Zheng W (2000) 2-amino-1-methyl-6-phenylimidazo[4, 5-b]pyridine, a carcinogen in high-temperature-cooked meat, and breast cancer risk. J Natl Cancer Inst 92:1352–1354CrossRefPubMedGoogle Scholar
  5. 5.
    Zheng W, Lee S (2009) Well-done meat intake, heterocyclic amine exposure, and cancer risk. Nutr Cancer 61:437–446CrossRefPubMedGoogle Scholar
  6. 6.
    Rohrmann S, Hermann S, Linseisen J (2009) Heterocyclic aromatic amine intake increases colorectal adenoma risk: findings from a prospective European cohort study. Am J Clin Nutr 89:1418–1424CrossRefPubMedGoogle Scholar
  7. 7.
    Koutros S, Cross AJ, Sandler DP et al (2008) Meat and meat mutagens and risk of prostate cancer in the agricultural Health study. Cancer Epidemiol Biomarkers Prev 17:80–87CrossRefPubMedGoogle Scholar
  8. 8.
    Norrish AE, Ferguson LR, Knize MG, Felton JS, Sharpe SJ, Jackson RT (1999) Heterocyclic amine content of cooked meat and risk of prostate cancer. J Natl Cancer Inst 91:2038–2044CrossRefPubMedGoogle Scholar
  9. 9.
    Cross AJ, Peters U, Kirsh VA et al (2005) A prospective study of meat and meat mutagens and prostate cancer risk. Cancer Res 65:11779–11784CrossRefPubMedGoogle Scholar
  10. 10.
    Sinha R, Park Y, Graubard BI et al (2009) Meat and meat-related compounds and risk of prostate cancer in a large prospective cohort study in the United States. Am J Epidemiol 170:1165–1177CrossRefPubMedGoogle Scholar
  11. 11.
    Rohrmann S, Platz EA, Kavanaugh CJ, Thuita L, Hoffman SC, Helzlsouer KJ (2007) Meat and dairy consumption and subsequent risk of prostate cancer in a US cohort study. Cancer Causes Control 18:41–50CrossRefPubMedGoogle Scholar
  12. 12.
    Cross AJ, Leitzmann MF, Gail MH, Hollenbeck AR, Schatzkin A, Sinha R (2007) A prospective study of red and processed meat intake in relation to cancer risk. PLoS Med 4:e325CrossRefPubMedGoogle Scholar
  13. 13.
    Michaud DS, Augustsson K, Rimm EB, Stampfer MJ, Willet WC, Giovannucci E (2001) A prospective study on intake of animal products and risk of prostate cancer. Cancer Causes Control 12:557–567CrossRefPubMedGoogle Scholar
  14. 14.
    Riboli E (2001) The European prospective investigation into cancer and nutrition (EPIC): plans and progress. J Nutr 131:170–175Google Scholar
  15. 15.
    Bergmann MM, Bussas U, Boeing H (1999) Follow-up procedures in EPIC-Germany-data quality aspects. European prospective investigation into cancer and nutrition. Ann Nutr Metab 43:225–234CrossRefPubMedGoogle Scholar
  16. 16.
    Bohlscheid Thomas S, Hoting I, Boeing H, Wahrendorf J (1997) Reproducibility and relative validity of food group intake in a food frequency questionnaire developed for the German part of the EPIC project. European prospective investigation into cancer and nutrition. Int J Epidemiol 26:59–70CrossRefGoogle Scholar
  17. 17.
    Rohrmann S, Zoller D, Hermann S, Lineisen J (2007) Intake of heterocyclic aromatic amines from meat in the European prospective investigation into cancer and nutrition (EPIC)-Heidelberg cohort. Br J Nutr 98:1112–1115CrossRefPubMedGoogle Scholar
  18. 18.
    Allen NE, Key TJ, Appleby PN et al (2008) Animal foods, protein, calcium and prostate cancer risk: the European prospective investigation into cancer and nutrition. Br J Cancer 98:1574–1581CrossRefPubMedGoogle Scholar
  19. 19.
    Skog K (2002) Problems associated with the determination of heterocyclic amines in cooked foods and human exposure. Food Chem Toxicol 40:1197–1203CrossRefPubMedGoogle Scholar
  20. 20.
    Sinha R (2002) An epidemiological approach to studying heterocyclic amines. Mutat Res 506–507:197–204PubMedGoogle Scholar
  21. 21.
    Kobayashi M, Hanaoka T, Tsugane S (2007) Validity of a self-administered food frequency questionnaire in the assessment of heterocyclic amine intake using 2-amino-1-methyl-6-phenylimidazo[4, 5-b]pyridine (PhIP) levels in hair. Mutat Res 630:14–19PubMedGoogle Scholar
  22. 22.
    Shirai T, Sano M, Tamano S et al (1997) The prostate: a target for carcinogenicity of 2-amino-1-methyl-6-phenylimidazo[4, 5-b]pyridine (PhIP) derived from cooked foods. Cancer Re 57:195–198Google Scholar
  23. 23.
    Tappel A (2007) Heme of consumed red meat can act as a catalyst of oxidative damage and could initiate colon, breast and prostate cancers, heart disease and other diseases. Med Hypotheses 68:562–564CrossRefPubMedGoogle Scholar
  24. 24.
    Koutros S, Brendt SI, Sinha R et al (2009) Xenobiotic metabolizing gene variants, dietary heterocyclic amine intake, and risk of prostate cancer. Cancer Res 69:1877–1884CrossRefPubMedGoogle Scholar

Copyright information

© Springer Science+Business Media B.V. 2010

Authors and Affiliations

  • Anja Sander
    • 1
    • 2
  • Jakob Linseisen
    • 1
    • 3
  • Sabine Rohrmann
    • 1
    • 4
    Email author
  1. 1.Division of Cancer EpidemiologyGerman Cancer Research CenterHeidelbergGermany
  2. 2.Department of MathematicsUniversity of BremenBremenGermany
  3. 3.Institute of EpidemiologyHelmholtz Centre MunichMunichGermany
  4. 4.Institute of Social and Preventive MedicineUniversity of ZurichZurichSwitzerland

Personalised recommendations