A large prospective study of meat consumption and colorectal cancer risk: an investigation of potential mechanisms underlying this association
Open accessAbstract
Although the relation between red and processed meat intake and colorectal cancer has been reported in several epidemiologic studies, very few investigated the potential mechanisms. This study examined multiple potential mechanisms in a large U.S. prospective cohort with a detailed questionnaire on meat type and meat cooking methods linked to databases for estimating intake of mutagens formed in meats cooked at high temperatures (heterocyclic amines, polycyclic aromatic hydrocarbons), heme iron, nitrate, and nitrite. During 7 years of follow-up, 2,719 colorectal cancer cases were ascertained from a cohort of 300,948 men and women. The hazard ratios (HR) and 95% confidence intervals (95% CI) comparing the fifth to the first quintile for both red (HR, 1.24; 95% CI, 1.09-1.42; P(trend) < 0.001) and processed meat (HR, 1.16; 95% CI, 1.01-1.32; P(trend) = 0.017) intakes indicated an elevated risk for colorectal cancer. The potential mechanisms for this relation include heme iron (HR, 1.13; 95% CI, 0.99-1.29; P(trend) = 0.022), nitrate from processed meats (HR, 1.16; 95% CI, 1.02-1.32; P(trend) = 0.001), and heterocyclic amine intake [HR, 1.19; 95% CI, 1.05-1.34; P(trend) < 0.001 for 2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline (MeIQx) and HR, 1.17; 95% CI, 1.05-1.29; P(trend) <0.001 for 2-amino-3,4,8-trimethylimidazo[4,5-f]quinoxaline (DiMeIQx)]. In general, the elevated risks were higher for rectal cancer than for colon cancer, with the exception of MeIQx and DiMeIQx, which were only associated with colon cancer. In conclusion, we found a positive association for red and processed meat intake and colorectal cancer; heme iron, nitrate/nitrite, and heterocyclic amines from meat may explain these associations.
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Nitrites in combination with dietary amines or amides, such as in red and cured meats, have been linked to stomach and several other cancers.
“Indeed, nitrites in combination with dietary amines or amides, such as in red and cured meats, have been linked to stomach and several other cancers[155,157,160,163–166].”
From Enterosalivary nitrate metabolism and the microbiome: Intersection of microbial metabolism, nitric oxide and diet in cardiac and pulmonary vascular health (2017) · cites this paper as [163]
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Cites
Food, nutrition, physical activity, and the prevention of cancer: a global perspective
Marmot, M. G., Atinmo, T., Byers, T., Chen, J., Hirohata, T., Jackson, A., James, W., Kolonel, L. N., Kumanyika, S., Leitzmann, C., et al. (2008) · Choice Reviews Online · doi:10.5860/choice.45-5024 · Cited by 5,365 · see citing works
Self-citationWillett, W. C. (1998) · doi:10.1093/acprof:oso/9780195122978.001.0001 · Cited by 4,541 · see citing works
Estimates of the worldwide incidence of 25 major cancers in 1990
Parkin, D. M., Pisani, P., & Ferlay, J. (1999) · International Journal of Cancer · doi:10.1002/(sici)1097-0215(19990315)80:6 · Cited by 2,013 · see citing works
Subar, A. F., Thompson, F. E., Kipnis, V., Midthune, D., Hurwitz, P. E., McNutt, S., McIntosh, A., & Rosenfeld, S. (2001) · American Journal of Epidemiology · doi:10.1093/aje/154.12.1089 · Cited by 1,401 · see citing works
Structure of Dietary Measurement Error: Results of the OPEN Biomarker Study
Kipnis, V. (2003) · American Journal of Epidemiology · doi:10.1093/aje/kwg091 · Cited by 868 · see citing works
Are there two sides to colorectal cancer?
Iacopetta, B. J. (2002) · International Journal of Cancer · doi:10.1002/ijc.10635 · Cited by 781 · see citing works
Design and Serendipity in Establishing a Large Cohort with Wide Dietary Intake Distributions
Schatzkin, A. G., Subar, A. F., Thompson, F. E., Harlan, L. C., Tangrea, J. A., Hollenbeck, A. R., Hurwitz, P. E., Coyle, L. M., Schussler, N., Michaud, D. S., et al. (2001) · American Journal of Epidemiology · doi:10.1093/aje/154.12.1119 · Cited by 611 · see citing works
Self-citationAnalysis of 200 food items for benzo[a]pyrene and estimation of its intake in an epidemiologic study
Kazerouni, N., Sinha, R. R., Hsu, C.-H., Greenberg, A., & Rothman, N. (2001) · Food and Chemical Toxicology · doi:10.1016/s0278-6915(00)00158-7 · Cited by 532 · see citing works
Self-citationLang, N. P., Butler, M. A., Massengill, J., Lawson, M., Stotts, R. C., Hauer‐Jensen, M., & Kadlubar, F. F. (1994) · PubMed · Cited by 391 · see citing works
(2003) · PubMed · Cited by 381 · see citing works
Carcinogenicities of heterocyclic amines in cooked food
Ohgaki, H., Takayama, S., & Sügimura, T. (1991) · Mutation Research/Genetic Toxicology · doi:10.1016/0165-1218(91)90130-e · Cited by 320 · see citing works
Subar, A. F. (2000) · American Journal of Epidemiology · doi:10.1093/aje/152.3.279 · Cited by 304 · see citing works
Sinha, R. R., Rothman, N., Salmon, C. P., Knize, M. G., Brown, E. D., Swanson, C. A., Rhodes, D., Rossi, S. C., Felton, J. S., & Levander, O. A. (1998) · Food and Chemical Toxicology · doi:10.1016/s0278-6915(97)00162-2 · Cited by 284 · see citing works
Self-citationA comparison of the tumors induced by coal tar and benzo[a]pyrene in a 2-year bioassay
Culp, S. (1998) · Carcinogenesis · doi:10.1093/carcin/19.1.117 · Cited by 284 · see citing works
Red meat and colon cancer: the cytotoxic and hyperproliferative effects of dietary heme.
Sesink, A. L. A., Termont, D. S., KLEIBEUKER, J. H., & van der Meer, R. (1999) · PubMed · Cited by 274 · see citing works
Sinha, R. R., Rothman, N., Brown, E. D., Salmon, C. P., Knize, M. G., Swanson, C. A., Rossi, S. C., Mark, S. D., Levander, O. A., & Felton, J. S. (1995) · PubMed · Cited by 269 · see citing works
Self-citationMeat, Meat Cooking Methods and Preservation, and Risk for Colorectal Adenoma
Sinha, R. R., Peters, U., Cross, A. J., Kulldorff, M., Weissfeld, J. L., Pinsky, P. F., Rothman, N., Hayes, R. B., & Prostate, L. (2005) · Cancer Research · doi:10.1158/0008-5472.can-04-3429 · Cited by 228 · see citing works
Self-citationSinha, R. R., Knize, M. G., Salmon, C. P., Brown, E. D., Rhodes, D., Felton, J. S., Levander, O. A., & Rothman, N. (1998) · Food and Chemical Toxicology · doi:10.1016/s0278-6915(97)00159-2 · Cited by 226 · see citing works
Self-citationNitrate in Public Water Supplies and the Risk of Colon and Rectum Cancers
Roos, A. J. D., Ward, M. H., Lynch, C. F., & Cantor, K. P. (2003) · Epidemiology · doi:10.1097/01.ede.0000091605.01334.d3 · Cited by 207 · see citing works
Self-citationHeme and Chlorophyll Intake and Risk of Colorectal Cancer in the Netherlands Cohort Study
Balder, H. F., Vogel, J., Jansen, M. C. J. F., Weijenberg, M. P., van den Brandt, P. A., Westenbrink, S., van der Meer, R., & Goldbohm, R. A. (2006) · Cancer Epidemiology Biomarkers & Prevention · doi:10.1158/1055-9965.epi-05-0772 · Cited by 205 · see citing works
Chemistry and biology of N-nitroso compounds
(1992) · International Journal of Biochemistry · doi:10.1016/0020-711x(92)90297-e · Cited by 187 · see citing works
Tappel, A. L. (2006) · Medical Hypotheses · doi:10.1016/j.mehy.2006.08.025 · Cited by 184 · see citing works
Marchand, L. L., Hankin, J. H., Wilkens, L. R., et al. (2001) · PubMed · Cited by 171 · see citing works
Heme Iron, Zinc, Alcohol Consumption, and Colon Cancer: Iowa Women's Health Study
Lee, D.-H., Anderson, K. E., Harnack, L., FOLSOM, A. R., & Jacobs, D. R. (2004) · JNCI Journal of the National Cancer Institute · doi:10.1093/jnci/djh047 · Cited by 162 · see citing works
Nowell, S. A., Coles, B., Sinha, R. R., Macleod, S. L., Ratnasinghe, D., Stotts, C., Kadlubar, F. F., Ambrosone, C. B., & Lang, N. P. (2002) · Mutation research. Fundamental and molecular mechanisms of mutagenesis · doi:10.1016/s0027-5107(02)00164-1 · Cited by 146 · see citing works
Self-citationDietary Benzo[a]Pyrene Intake and Risk of Colorectal Adenoma
Sinha, R. R., Kulldorff, M., Gunter, M. J., et al. (2005) · Cancer Epidemiology Biomarkers & Prevention · doi:10.1158/1055-9965.epi-04-0854 · Cited by 146 · see citing works
Self-citationPierre, F., Taché, S., Corpet, D. E., Freeman, A., & van der Meer, R. (2004) · Journal of Nutrition · doi:10.1093/jn/134.10.2711 · Cited by 143 · see citing works
Chemistry and biology of N-nitroso compounds
(1993) · Comparative Biochemistry and Physiology Part A Physiology · doi:10.1016/0300-9629(93)90336-3 · Cited by 122 · see citing works
Iron-overload induces oxidative DNA damage in the human colon carcinoma cell line HT29 clone 19A
Glei, M., Latunde-Dada, G. O., Klinder, A., Becker, T. W., Hermann, U. S., Voigt, K., & Pool-Zobel, B. L. (2002) · Mutation Research/Genetic Toxicology and Environmental Mutagenesis · doi:10.1016/s1383-5718(02)00135-3 · Cited by 121 · see citing works
A cohort study of dietary iron and heme iron intake and risk of colorectal cancer in women
Kabat, G. C., Miller, A. B., Jain, M., & Rohan, T. E. (2007) · British Journal of Cancer · doi:10.1038/sj.bjc.6603837 · Cited by 117 · see citing works
Sinha, R. R., Cross, A. J., Curtin, J., Zimmerman, T. P., McNutt, S., Risch, A., & Holden, J. M. (2005) · Molecular Nutrition & Food Research · doi:10.1002/mnfr.200500018 · Cited by 115 · see citing works
Self-citationGenetic polymorphisms in heterocyclic amine metabolism and risk of colorectal adenomas
Ishibe, N., Sinha, R. R., Hein, D. W., Kulldorff, M., Strickland, P. T., Fretland, A. J., Chow, W., Kadlubar, F. F., Lang, N. P., & Rothman, N. (2002) · Pharmacogenetics · doi:10.1097/00008571-200203000-00008 · Cited by 111 · see citing works
Self-citationNitrate in Public Water Supplies and Risk of Bladder Cancer
Ward, M. H., Cantor, K. P., Riley, D. G., Merkle, S., & Lynch, C. F. (2003) · Epidemiology · doi:10.1097/01.ede.0000050664.28048.df · Cited by 100 · see citing works
Self-citationNöthlings, U., Yamamoto, J. F., Wilkens, L. R., Murphy, S. P., Park, S., Henderson, B. E., Kolonel, L. N., & Marchand, L. L. (2009) · Cancer Epidemiology Biomarkers & Prevention · doi:10.1158/1055-9965.epi-08-1218 · Cited by 99 · see citing works
Sesink, A. L. A. (2000) · Carcinogenesis · doi:10.1093/carcin/21.10.1909 · Cited by 95 · see citing works
Red meat intake, CYP2E1 genetic polymorphisms, and colorectal cancer risk.
Marchand, L. L., Donlon, T. A., Seifried, A., et al. (2002) · PubMed · Cited by 92 · see citing works
Butler, L. M., Duguay, Y., Millikan, R. C., Sinha, R. R., Gagné, J.-F., Sandler, R. S., & Guillemette, C. (2005) · Cancer Epidemiology Biomarkers & Prevention · doi:10.1158/1055-9965.epi-04-0682 · Cited by 69 · see citing works
Self-citationRisk of Non-Hodgkin Lymphoma and Nitrate and Nitrite From Drinking Water and Diet
Ward, M. H., Cerhan, J. R., Colt, J. S., & Hartge, P. (2006) · Epidemiology · doi:10.1097/01.ede.0000219675.79395.9f · Cited by 67 · see citing works
Self-citationProcessed meat intake, CYP2A6 activity and risk of colorectal adenoma
Ward, M. H., Cross, A. J., Divan, H. A., Kulldorff, M., Kadlubar, S. N., Kadlubar, F. F., & Sinha, R. R. (2007) · Carcinogenesis · doi:10.1093/carcin/bgm009 · Cited by 66 · see citing works
Self-citationShin, A., Shrubsole, M. J., Rice, J. M., Cai, Q., Doll, M. A., Long, J., Smalley, W. E., Shyr, Y., Sinha, R. R., Ness, R. M., et al. (2008) · Cancer Epidemiology Biomarkers & Prevention · doi:10.1158/1055-9965.epi-07-0615 · Cited by 64 · see citing works
Self-citationDietary Meat Intake in Relation to Colorectal Adenoma in Asymptomatic Women
Ferrucci, L. M., Sinha, R. R., Graubard, B. I., et al. (2009) · The American Journal of Gastroenterology · doi:10.1038/ajg.2009.102 · Cited by 64 · see citing works
Self-citation
Flagged first, then by citations
Research works printed but not linked: 1
- [21]International Classification of Diseases for Oncology: Third edition 2000 World Health Organization Geneva
Cited by
Sorted by citations
Chemical transformation of xenobiotics by the human gut microbiota
Koppel, N., Maini Rekdal, V., & Balskus, E. P. (2017) · Science · doi:10.1126/science.aag2770 · Cited by 1,080 · see citing works
Red and Processed Meat and Colorectal Cancer Incidence: Meta-Analysis of Prospective Studies
Chan, D. S. M., Lau, R., Aune, D., Vieira, R., Greenwood, D. C., Kampman, E., & Norat, T. (2011) · PLoS ONE · doi:10.1371/journal.pone.0020456 · Cited by 903 · see citing works
Nutrients, foods, and colorectal cancer prevention
Song, M., Garrett, W. S., & Chan, A. T. (2015) · Gastroenterology · doi:10.1053/j.gastro.2014.12.035 · Cited by 700 · see citing works
Trends in meat consumption in the USA
Daniel, C. R., Cross, A. J., Koebnick, C., & Sinha, R. (2011) · Public Health Nutrition · doi:10.1017/s1368980010002077 · Cited by 504 · see citing works
Self-citationTorti, S. V., Manz, D. H., Paul, B. T., Blanchette-Farra, N., & Torti, F. M. (2018) · Annual Review of Nutrition · doi:10.1146/annurev-nutr-082117-051732 · Cited by 426 · see citing works
Bastide, N. M., Pierre, F. H. F., & Corpet, D. E. (2011) · Cancer Prevention Research · doi:10.1158/1940-6207.capr-10-0113 · Cited by 397 · see citing works
Nitrates/Nitrites in Food—Risk for Nitrosative Stress and Benefits
Karwowska, M., & Kononiuk, A. (2020) · Antioxidants · doi:10.3390/antiox9030241 · Cited by 360 · see citing works
Gut Microbiota and Iron: The Crucial Actors in Health and Disease
Yilmaz, B., & Li, H. (2018) · Pharmaceuticals · doi:10.3390/ph11040098 · Cited by 317 · see citing works
Host-microbial interactions in the metabolism of therapeutic and diet-derived xenobiotics
Carmody, R. N., & Turnbaugh, P. J. (2014) · Journal of Clinical Investigation · doi:10.1172/jci72335 · Cited by 268 · see citing works
Koch, C. D., Gladwin, M. T., Freeman, B. A., Lundberg, J. O., Weitzberg, E., & Morris, A. (2017) · Free Radical Biology and Medicine · doi:10.1016/j.freeradbiomed.2016.12.015 · Cited by 186 · see citing works
Alisson-Silva, F., Kawanishi, K., & Varki, A. (2016) · Molecular Aspects of Medicine · doi:10.1016/j.mam.2016.07.002 · Cited by 156 · see citing works
Chazelas, E., Pierre, F., Druesne-Pecollo, N., Esseddik, Y., Szabo de Edelenyi, F., Agaesse, C., De Sa, A., Lutchia, R., Gigandet, S., Srour, B., et al. (2022) · International Journal of Epidemiology · doi:10.1093/ije/dyac046 · Cited by 135 · see citing works
Guertin, K. A., Li, X. S., Graubard, B. I., Albanes, D., Weinstein, S. J., Goedert, J. J., Wang, Z., Hazen, S. L., & Sinha, R. (2017) · Cancer Epidemiology, Biomarkers & Prevention · doi:10.1158/1055-9965.epi-16-0948 · Cited by 96 · see citing works
Self-citationNitrite and nitrate: cardiovascular risk–benefit and metabolic effect
Tang, Y., Jiang, H., & Bryan, N. S. (2011) · Current Opinion in Lipidology · doi:10.1097/mol.0b013e328341942c · Cited by 69 · see citing works
Ungvari, Z., Fekete, M., Varga, P., Lehoczki, A., Munkácsy, G., Fekete, J. T., Bianchini, G., Ocana, A., Buda, A., Ungvari, A., et al. (2025) · GeroScience · doi:10.1007/s11357-025-01646-1 · Cited by 56 · see citing works
A “green” diet-based approach to cardiovascular health? Is inorganic nitrate the answer?
Rathod, K. S., Velmurugan, S., & Ahluwalia, A. (2016) · Molecular Nutrition & Food Research · doi:10.1002/mnfr.201500313 · Cited by 42 · see citing works
- Authors
- Cross, A. J., Ferrucci, L. M., Risch, A., Graubard, B. I., Ward, M. H., Park, Y., Hollenbeck, A. R., Schatzkin, A., & Sinha, R.
- Affiliations
- National Institutes of Health (US)
- Corresponding author
- Cross, Amanda J.
- ORCID
- Venue
- Cancer Research
- Published
- 2010-03-14
- Volume
- 70
- Issue
- 6
- Pages
- 2406-2414
- ISSN
- 0008-5472 (ISSN-L)
- 1538-7445
- PMC
- PMC2840051
- OpenAlex
- W2161337548
- Cited by
- 469
- References
- 41
- Citations by year
- 2026: 15 · 2025: 23 · 2024: 17 · 2023: 31 · 2022: 32 · 2021: 29 · 2020: 34 · 2019: 36 · 2018: 19 · 2017: 29 · 2016: 47 · 2015: 29 · 2014: 28 · 2013: 40 · 2012: 23
- FWCI
- 31.04
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Cancer Research (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institutes of Health (Z99 CA999999)
- Topics
- Health Sciences › Medicine › Public Health, Environmental and Occupational Health › Nutritional Studies and Diet
- Health Sciences › Medicine › Oncology › Colorectal Cancer Screening and Detection
- Life Sciences › Agricultural and Biological Sciences › Animal Science and Zoology › Meat and Animal Product Quality
- Keywords
- red meat consumption, processed meat consumption, colorectal cancer risk, heme iron, nitrate, nitrite, heterocyclic amines, polycyclic aromatic hydrocarbons, high-temperature cooking, MeIQx, rectal cancer, colon cancer, cancer mechanisms, prospective cohort, cancer screening, cancer survivorship
- MeSH terms
- Cooking, Diet, Female, Humans, Imidazoles, Male, Meat, Middle Aged, Prospective Studies, Surveys and Questionnaires, Quinoxalines, United States, Colorectal Neoplasms, Cohort Studies
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