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Chemicals in Meat Cooked at High Temperatures and Cancer Risk

Key Points

  • Heterocyclic amines (HCAs) and polycyclic aromatic hydrocarbons (PAHs) are chemicals formed when muscle meat, including beef, pork, fish, and poultry, is cooked using high-temperature methods, such as pan frying or grilling directly over an open flame.
  • The formation of HCAs and PAHs is influenced by the type of meat, the cooking time, the cooking temperature, and the cooking method.
  • Exposure to high levels of HCAs and PAHs can cause cancer in animals; however, whether such exposure causes cancer in humans is unclear.
  • Currently, no Federal guidelines address consumption levels of HCAs and PAHs formed in meat.
  • HCA and PAH formation can be reduced by avoiding direct exposure of meat to an open flame or a hot metal surface, reducing the cooking time, and using a microwave oven to partially cook meat before exposing it to high temperatures.
  • Ongoing studies are investigating the associations between meat intake, meat cooking methods, and cancer risk.
  1. What are heterocyclic amines and polycyclic aromatic hydrocarbons, and how are they formed in cooked meats?

    Heterocyclic amines (HCAs) and polycyclic aromatic hydrocarbons (PAHs) are chemicals formed when muscle meat, including beef, pork, fish, or poultry, is cooked using high-temperature methods, such as pan frying or grilling directly over an open flame (1). In laboratory experiments, HCAs and PAHs have been found to be mutagenic—that is, they cause changes in DNA that may increase the risk of cancer.

    HCAs are formed when amino acids (the building blocks of proteins), sugars, and creatine (a substance found in muscle) react at high temperatures. PAHs are formed when fat and juices from meat grilled directly over an open fire drip onto the fire, causing flames. These flames contain PAHs that then adhere to the surface of the meat. PAHs can also be formed during other food preparation processes, such as smoking of meats (1).

    HCAs are not found in significant amounts in foods other than meat cooked at high temperatures. PAHs can be found in other charred foods, as well as in cigarette smoke and car exhaust fumes.

  2. What factors influence the formation of HCA and PAH in cooked meats?

    The formation of HCAs and PAHs varies by meat type, cooking method, and “doneness” level (rare, medium, or well done). Whatever the type of meat, however, meats cooked at high temperatures, especially above 300ºF (as in grilling or pan frying), or that are cooked for a long time tend to form more HCAs. For example, well done, grilled, or barbecued chicken and steak all have high concentrations of HCAs. Cooking methods that expose meat to smoke or charring contribute to PAH formation (2).

    HCAs and PAHs become capable of damaging DNA only after they are metabolized by specific enzymes in the body, a process called “bioactivation.” Studies have found that the activity of these enzymes, which can differ among people, may be relevant to cancer risks associated with exposure to these compounds (35).

  3. What evidence is there that HCAs and PAHs in cooked meats may increase cancer risk?

    Studies have shown that exposure to HCAs and PAHs can cause cancer in animal models (6). In many experiments, rodents fed a diet supplemented with HCAs developed tumors of the breast, colon, liver, skin, lung, prostate, and other organs (712). Rodents fed PAHs also developed cancers, including leukemia and tumors of the gastrointestinal tract and lungs (13). However, the doses of HCAs and PAHs used in these studies were very high—equivalent to thousands of times the doses that a person would consume in a normal diet.

    Population studies have not established a definitive link between HCA and PAH exposure from cooked meats and cancer in humans. One difficulty with conducting such studies is that it can be difficult to determine the exact level of HCA and/or PAH exposure a person gets from cooked meats. Although dietary questionnaires can provide good estimates, they may not capture all the detail about cooking techniques that is necessary to determine HCA and PAH exposure levels. In addition, individual variation in the activity of enzymes that metabolize HCAs and PAHs may result in exposure differences, even among people who ingest (take in) the same amount of these compounds. Also, people may have been exposed to PAHs from other environmental sources, such as pollution and tobacco smoke.

    Nevertheless, numerous epidemiologic studies have used detailed questionnaires to examine participants’ meat consumption and meat cooking methods to estimate HCA and PAH exposures. Researchers found that high consumption of well-done, fried, or barbecued meats was associated with increased risks of colorectal (14), pancreatic (15, 16), and prostate (17, 18) cancer.

  4. Do guidelines exist for the consumption of food containing HCAs and PAHs?

    Currently, no Federal guidelines address the consumption of foods containing HCAs and PAHs. The World Cancer Research Fund/American Institute for Cancer Research issued a report in 2007 with dietary guidelines that recommended limiting the consumption of red and processed (including smoked) meats; however, no recommendations were provided for HCA and PAH levels in meat (19).

  5. Are there ways to reduce HCA and PAH formation in cooked meats?

    Even though no specific guidelines for HCA/PAH consumption exist, concerned individuals can reduce their exposure by using several cooking methods:

    • Avoiding direct exposure of meat to an open flame or a hot metal surface and avoiding prolonged cooking times (especially at high temperatures) can help reduce HCA and PAH formation (20).
    • Using a microwave oven to cook meat prior to exposure to high temperatures can also substantially reduce HCA formation by reducing the time that meat must be in contact with high heat to finish cooking (20).
    • Continuously turning meat over on a high heat source can substantially reduce HCA formation compared with just leaving the meat on the heat source without flipping it often (20).
    • Removing charred portions of meat and refraining from using gravy made from meat drippings can also reduce HCA and PAH exposure (20).

  6. What research is being conducted on the relationship between the consumption of HCAs and PAHs and cancer risk in humans?

    Researchers in the United States are currently investigating the association between meat intake, meat cooking methods, and cancer risk. Ongoing studies include the NIH-AARP Diet and Health Study (14, 21), the American Cancer Society’s Cancer Prevention Study II (22), the Multiethnic Cohort (23), and studies from Harvard University (24). Similar research in a European population is being conducted in the European Prospective Investigation into Cancer and Nutrition (EPIC) study (25).

Selected References
  1. Cross AJ, Sinha R. Meat-related mutagens/carcinogens in the etiology of colorectal cancer. Environmental and Molecular Mutagenesis 2004; 44(1):44–55. [PubMed Abstract]
  2. Jägerstad M, Skog K. Genotoxicity of heat-processed foods. Mutation Research 2005; 574(1–2):156–172. [PubMed Abstract]
  3. Sinha R, Rothman N, Mark SD, et al. Lower levels of urinary 2-amino-3,8-dimethylimidazo[4,5-f]-quinoxaline (MeIQx) in humans with higher CYP1A2 activity. Carcinogenesis 1995; 16(11):2859–2861. [PubMed Abstract]
  4. Moonen H, Engels L, Kleinjans J, Kok T. The CYP1A2-164A-->C polymorphism (CYP1A2*1F) is associated with the risk for colorectal adenomas in humans. Cancer Letters 2005; 229(1):25–31. [PubMed Abstract]
  5. Butler LM, Duguay Y, Millikan RC, et al. Joint effects between UDP-glucuronosyltransferase 1A7 genotype and dietary carcinogen exposure on risk of colon cancer. Cancer Epidemiology, Biomarkers and Prevention 2005; 14(7):1626–1632. [PubMed Abstract]
  6. Sugimura T, Wakabayashi K, Nakagama H, Nagao M. Heterocyclic amines: Mutagens/carcinogens produced during cooking of meat and fish. Cancer Science 2004; 95(4):290–299. [PubMed Abstract]
  7. Ito N, Hasegawa R, Sano M, et al. A new colon and mammary carcinogen in cooked food, 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP). Carcinogenesis 1991; 12(8):1503–1506. [PubMed Abstract]
  8. Kato T, Ohgaki H, Hasegawa H, et al. Carcinogenicity in rats of a mutagenic compound, 2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline. Carcinogenesis 1988; 9(1):71–73. [PubMed Abstract]
  9. Kato T, Migita H, Ohgaki H, et al. Induction of tumors in the Zymbal gland, oral cavity, colon, skin and mammary gland of F344 rats by a mutagenic compound, 2-amino-3,4-dimethylimidazo[4,5-f]quinoline. Carcinogenesis 1989; 10(3):601–603. [PubMed Abstract]
  10. Ohgaki H, Kusama K, Matsukura N, et al. Carcinogenicity in mice of a mutagenic compound, 2-amino-3-methylimidazo[4,5-f]quinoline, from broiled sardine, cooked beef and beef extract. Carcinogenesis 1984; 5(7):921–924. [PubMed Abstract]
  11. Ohgaki H, Hasegawa H, Suenaga M, et al. Induction of hepatocellular carcinoma and highly metastatic squamous cell carcinomas in the forestomach of mice by feeding 2-amino-3,4-dimethylimidazo[4,5-f]quinoline. Carcinogenesis 1986; 7(11):1889–1893. [PubMed Abstract]
  12. Shirai T, Sano M, Tamano S, et al. The prostate: A target for carcinogenicity of 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) derived from cooked foods. Cancer Research 1997; 57(2):195–198. [PubMed Abstract]
  13. Committee on Diet, Nutrition, and Cancer, Assembly of Life Sciences, National Research Council. Diet, Nutrition and Cancer. National Academy Press, Washington D.C. 1982. Retrieved September 27, 2010, from: http://www.nap.edu/openbook.php?record_id=371&page=1.

  14. Cross AJ, Ferrucci LM, Risch A, et al. A large prospective study of meat consumption and colorectal cancer risk: An investigation of potential mechanisms underlying this association. Cancer Research 2010; 70(6):2406–2414. [PubMed Abstract]
  15. Anderson KE, Sinha R, Kulldorff M, et al. Meat intake and cooking techniques: Associations with pancreatic cancer. Mutation Research 2002; 506–507:225–231. [PubMed Abstract]
  16. Stolzenberg-Solomon RZ, Cross AJ, Silverman DT, et al. Meat and meat-mutagen intake and pancreatic cancer risk in the NIH-AARP cohort. Cancer Epidemiology, Biomarkers, and Prevention 2007; 16(12):2664–2675. [PubMed Abstract]
  17. Cross AJ, Peters U, Kirsh VA, et al. A prospective study of meat and meat mutagens and prostate cancer risk. Cancer Research 2005; 65(24):11779–11784. [PubMed Abstract]
  18. Sinha R, Park Y, Graubard BI, et al. Meat and meat-related compounds and risk of prostate cancer in a large prospective cohort study in the United States. American Journal of Epidemiology 2009; 170(9):1165–1177. [PubMed Abstract]
  19. WCRF/AICR Expert Report. Food, Nutrition, Physical Activity and the Prevention of Cancer: A Global Perspective 2007. Retrieved September 27, 2010, from: http://www.dietandcancerreport.org/.

  20. Knize MG, Felton JS. Formation and human risk of carcinogenic heterocyclic amines formed from natural precursors in meat. Nutrition Reviews 2005; 63(5):158–165. [PubMed Abstract]
  21. Kabat GC, Cross AJ, Park Y, et al. Meat intake and meat preparation in relation to risk of postmenopausal breast cancer in the NIH-AARP diet and health study. International Journal of Cancer 2009; 124(10):2430–2435. [PubMed Abstract]
  22. Rodriguez C, McCullough ML, Mondul AM, et al. Meat consumption among Black and White men and risk of prostate cancer in the Cancer Prevention Study II Nutrition Cohort. Cancer Epidemiology, Biomarkers and Prevention 2006; 15(2):211–216. [PubMed Abstract]

  23. Nöthlings U, Yamamoto JF, Wilkens LR, et al. Meat and heterocyclic amine intake, smoking, NAT1 and NAT2 polymorphisms, and colorectal cancer risk in the multiethnic cohort study. Cancer Epidemiology, Biomarkers and Prevention 2009; 18(7):2098–2106. [PubMed Abstract]
  24. Wu K, Sinha R, Holmes M, et al. Meat mutagens and breast cancer in postmenopausal women—A cohort analysis. Cancer Epidemiology, Biomarkers and Prevention 2010; 19(5):1301–1310. [PubMed Abstract]
  25. Rohrmann S, Zoller D, Hermann S, Linseisen J. Intake of heterocyclic aromatic amines from meat in the European Prospective Investigation into Cancer and Nutrition (EPIC)-Heidelberg cohort. British Journal of Nutrition 2007; 98(6):1112–1115. [PubMed Abstract]
  • Reviewed: October 15, 2010