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Associations of red and processed meat intake with major molecular pathological features of colorectal cancer

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Abstract

Red and processed meat is an established risk factor for colorectal cancer (CRC). However, exact mechanisms to explain the associations remain unclear. Few studies have investigated the association with CRC by molecular tumor features, which could provide relevant information on associated molecular pathways. In this population-based case–control study from Germany (DACHS), 2449 cases and 2479 controls provided information on risk factors of CRC and completed a food frequency questionnaire. Multivariable logistic regression was used to estimate odds ratios (ORs) and 95% confidence intervals (CI) for the associations between meat intake and risk of CRC by molecular pathologic features and specific subtypes. Red and processed meat intake was associated with increased risk of colorectal (>1 time/day vs ≤1 time/week OR 1.66, 95% CI 1.34–2.07), colon and rectal cancer. Among the single molecular tumor features investigated, the results were similar for associations of red and processed meat with CRC risk by microsatellite instability, CpG island methylator phenotype, BRAF, oestrogen receptor-β and p53 status. Red and processed meat intake was associated less strongly with risk of KRAS-mutated CRC (OR >1 time/day vs ≤1 time/week: 1.49, 95% CI 1.09–2.03) than with risk of KRAS-wildtype CRC (OR 1.82, 95% CI 1.42–2.34; p heterogeneity 0.04). These results support an association between red and processed meat and CRC risk similar for subsites of CRC and most of the investigated major molecular pathological features. Potential differences were observed in more specific subtype analyses. Further large studies are needed to confirm these results and to help further elucidate potential underlying mechanisms.

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References

  1. Ogino S, Chan AT, Fuchs CS, Giovannucci E. Molecular pathological epidemiology of colorectal neoplasia: an emerging transdisciplinary and interdisciplinary field. Gut. 2011;60(3):397–411.

    Article  PubMed  Google Scholar 

  2. Ogino S, Nishihara R, VanderWeele TJ, et al. Review article: the role of molecular pathological epidemiology in the study of neoplastic and non-neoplastic diseases in the era of precision medicine. Epidemiology. 2016;27(4):602–11.

    Article  PubMed  PubMed Central  Google Scholar 

  3. Chan DS, Lau R, Aune D, et al. Red and processed meat and colorectal cancer incidence: meta-analysis of prospective studies. PLoS ONE. 2011;6(6):e20456.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  4. World Cancer Research Fund/American Institute for Cancer Research. Food, Nutrition, Physical Activity, and the Prevention of Cancer: a Global Perspective. In. Washington DC; 2007.

  5. World Cancer Research Fund/American Institute for Cancer Research. Continuous Update Project Report. Food, Nutrition, Physical Activity, and the Prevention of Colorectal Cancer. In; 2011

  6. Bouvard V, Loomis D, Guyton KZ, et al. Carcinogenicity of consumption of red and processed meat. Lancet Oncol. 2015;16(16):1599–600.

    Article  PubMed  Google Scholar 

  7. Hammerling U, Bergman Laurila J, Grafstrom R, Ilback NG. Consumption of Red/processed meat and colorectal carcinoma: possible mechanisms underlying the significant association. Crit Rev Food Sci Nutr. 2016;56(4):614–34.

    Article  CAS  PubMed  Google Scholar 

  8. Brink M, Weijenberg MP, de Goeij AF, et al. Meat consumption and K-ras mutations in sporadic colon and rectal cancer in The Netherlands Cohort Study. Br J Cancer. 2005;92(7):1310–20.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  9. Slattery ML, Curtin K, Anderson K, et al. Associations between dietary intake and Ki-ras mutations in colon tumors: a population-based study. Cancer Res. 2000;60(24):6935–41.

    CAS  PubMed  Google Scholar 

  10. Slattery ML, Curtin K, Ma K, et al. Diet activity, and lifestyle associations with p53 mutations in colon tumors. Cancer Epidemiol Biomarkers Prev. 2002;11(6):541–8.

    CAS  PubMed  Google Scholar 

  11. Voskuil DW, Kampman E, van Kraats AA, et al. p53 over-expression and p53 mutations in colon carcinomas: relation to dietary risk factors. Int J Cancer. 1999;81(5):675–81.

    Article  CAS  PubMed  Google Scholar 

  12. Freedman AN, Michalek AM, Marshall JR, et al. Familial and nutritional risk factors for p53 overexpression in colorectal cancer. Cancer Epidemiol Biomarkers Prev. 1996;5(4):285–91.

    CAS  PubMed  Google Scholar 

  13. Mrkonjic M, Chappell E, Pethe VV, et al. Association of apolipoprotein E polymorphisms and dietary factors in colorectal cancer. Br J Cancer. 2009;100(12):1966–74.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  14. Satia JA, Keku T, Galanko JA, et al. Diet, lifestyle, and genomic instability in the North Carolina Colon Cancer Study. Cancer Epidemiol Biomarkers Prev. 2005;14(2):429–36.

    Article  CAS  PubMed  Google Scholar 

  15. Diergaarde B, Braam H, van Muijen GN, Ligtenberg MJ, Kok FJ, Kampman E. Dietary factors and microsatellite instability in sporadic colon carcinomas. Cancer Epidemiol Biomarkers Prev. 2003;12(11 Pt 1):1130–6.

    CAS  PubMed  Google Scholar 

  16. Joshi AD, Kim A, Lewinger JP, et al. Meat intake, cooking methods, dietary carcinogens, and colorectal cancer risk: findings from the Colorectal Cancer Family Registry. Cancer Med. 2015;4(6):936–52.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  17. Wu AH, Shibata D, Yu MC, Lai MY, Ross RK. Dietary heterocyclic amines and microsatellite instability in colon adenocarcinomas. Carcinogenesis. 2001;22(10):1681–4.

    Article  CAS  PubMed  Google Scholar 

  18. Slattery ML, Anderson K, Curtin K, Ma KN, Schaffer D, Samowitz W. Dietary intake and microsatellite instability in colon tumors. Int J Cancer. 2001;93(4):601–7.

    Article  CAS  PubMed  Google Scholar 

  19. Kampman E, Voskuil DW, van Kraats AA, et al. Animal products and K-ras codon 12 and 13 mutations in colon carcinomas. Carcinogenesis. 2000;21(2):307–9.

    Article  CAS  PubMed  Google Scholar 

  20. Slattery ML, Curtin K, Wolff RK, Herrick JS, Caan BJ, Samowitz W. Diet, physical activity, and body size associations with rectal tumor mutations and epigenetic changes. Cancer Causes Control. 2010;21(8):1237–45.

    Article  PubMed  PubMed Central  Google Scholar 

  21. Brenner H, Chang-Claude J, Seiler CM, Rickert A, Hoffmeister M. Protection from colorectal cancer after colonoscopy: a population-based, case-control study. Ann Intern Med. 2011;154(1):22–30.

    Article  PubMed  Google Scholar 

  22. Brenner H, Chang-Claude J, Rickert A, Seiler CM, Hoffmeister M. Risk of colorectal cancer after detection and removal of adenomas at colonoscopy: population-based case-control study. J Clin Oncol. 2012;30(24):2969–76.

    Article  PubMed  Google Scholar 

  23. Findeisen P, Kloor M, Merx S, et al. T25 repeat in the 3′ untranslated region of the CASP2 gene: a sensitive and specific marker for microsatellite instability in colorectal cancer. Cancer Res. 2005;65(18):8072–8.

    Article  CAS  PubMed  Google Scholar 

  24. Hoffmeister M, Blaker H, Kloor M, et al. Body mass index and microsatellite instability in colorectal cancer: a population-based study. Cancer Epidemiol Biomarkers Prev. 2013;22(12):2303–11.

    Article  CAS  PubMed  Google Scholar 

  25. Jia M, Jansen L, Walter V, et al. No association of CpG island methylator phenotype and colorectal cancer survival: population-based study. Br J Cancer. 2016;. doi:10.1038/bjc.2016.361.

    PubMed Central  Google Scholar 

  26. Warth A, Kloor M, Schirmacher P, Blaker H. Genetics and epigenetics of small bowel adenocarcinoma: the interactions of CIN, MSI, and CIMP. Mod Pathol. 2011;24(4):564–70.

    Article  CAS  PubMed  Google Scholar 

  27. Rudolph A, Toth C, Hoffmeister M, et al. Colorectal cancer risk associated with hormone use varies by expression of estrogen receptor-beta. Cancer Res. 2013;73(11):3306–15.

    Article  CAS  PubMed  Google Scholar 

  28. Yuan Y. Multiple imputation using SAS software. J Stat Softw. 2011;45(6):1–25.

    Article  Google Scholar 

  29. Jass JR. Classification of colorectal cancer based on correlation of clinical, morphological and molecular features. Histopathology. 2007;50(1):113–30.

    Article  CAS  PubMed  Google Scholar 

  30. Whitehall VL, Wynter CV, Walsh MD, et al. Morphological and molecular heterogeneity within nonmicrosatellite instability-high colorectal cancer. Cancer Res. 2002;62(21):6011–4.

    CAS  PubMed  Google Scholar 

  31. Kambara T, Simms LA, Whitehall VL, et al. BRAF mutation is associated with DNA methylation in serrated polyps and cancers of the colorectum. Gut. 2004;53(8):1137–44.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  32. Norat T, Lukanova A, Ferrari P, Riboli E. Meat consumption and colorectal cancer risk: dose-response meta-analysis of epidemiological studies. Int J Cancer. 2002;98(2):241–56.

    Article  CAS  PubMed  Google Scholar 

  33. Norat T, Riboli E. Meat consumption and colorectal cancer: a review of epidemiologic evidence. Nutr Rev. 2001;59(2):37–47.

    Article  CAS  PubMed  Google Scholar 

  34. Larsson SC, Wolk A. Meat consumption and risk of colorectal cancer: a meta-analysis of prospective studies. Int J Cancer. 2006;119(11):2657–64.

    Article  CAS  PubMed  Google Scholar 

  35. Sandhu MS, White IR, McPherson K. Systematic review of the prospective cohort studies on meat consumption and colorectal cancer risk: a meta-analytical approach. Cancer Epidemiol Biomarkers Prev. 2001;10(5):439–46.

    CAS  PubMed  Google Scholar 

  36. Carr PR, Walter V, Brenner H, Hoffmeister M. Meat subtypes and their association with colorectal cancer: systematic review and meta-analysis. Int J Cancer. 2016;138(2):293–302.

    Article  CAS  PubMed  Google Scholar 

  37. Miller PE, Lazarus P, Lesko SM, et al. Meat-related compounds and colorectal cancer risk by anatomical subsite. Nutr Cancer. 2013;65(2):202–26.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  38. Bernstein AM, Song M, Zhang X, et al. Processed and unprocessed red meat and risk of colorectal cancer: analysis by tumor location and modification by time. PLoS ONE. 2015;10(8):e0135959.

    Article  PubMed  PubMed Central  Google Scholar 

  39. Ollberding NJ, Wilkens LR, Henderson BE, Kolonel LN, Le Marchand L. Meat consumption, heterocyclic amines and colorectal cancer risk: the Multiethnic Cohort Study. Int J Cancer. 2012;131(7):E1125–33.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  40. Parr CL, Hjartaker A, Lund E, Veierod MB. Meat intake, cooking methods and risk of proximal colon, distal colon and rectal cancer: the Norwegian Women and Cancer (NOWAC) cohort study. Int J Cancer. 2013;133(5):1153–63.

    Article  CAS  PubMed  Google Scholar 

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Acknowledgements

The authors thank Ute Handte-Daub, Ansgar Brandhorst and Petra Bächer for their excellent technical assistance. The authors thank the study participants and the interviewers who collected the data. The authors also thank the following hospitals and cooperating institutions that recruited patients for this study: Chirurgische Universitätsklinik Heidelberg, Klinik am Gesundbrunnen Heilbronn, St. Vincentiuskrankenhaus Speyer, St. Josefskrankenhaus Heidelberg, Chirurgische Universitätsklinik Mannheim, Diakonissenkrankenhaus Speyer, Krankenhaus Salem Heidelberg, Kreiskrankenhaus Schwetzingen, St. Marienkrankenhaus Ludwigshafen, Klinikum Ludwigshafen, Stadtklinik Frankenthal, Diakoniekrankenhaus Mannheim, Kreiskrankenhaus Sinsheim, Klinikum am Plattenwald Bad Friedrichshall, Kreiskrankenhaus Weinheim, Kreiskrankenhaus Eberbach, Kreiskrankenhaus Buchen, Kreiskrankenhaus Mosbach, Enddarmzentrum Mannheim, Kreiskrankenhaus Brackenheim, and Cancer Registry of Rhineland-Palatinate, Mainz. We are also very grateful for the support of the pathologies in the provision of tumour samples: Institut für Pathologie, Universitätsklinik Heidelberg; Institut für Pathologie, Klinikum Heilbronn; Institut für Angewandte Pathologie, Speyer; Pathologisches Institut, Universitätsklinikum Mannheim; Institut für Pathologie, Klinikum Ludwigshafen; Institut für Pathologie, Klinikum Stuttgart; Institut für Pathologie, Klinikum Ludwigsburg. Special thanks to the tissue bank of National Center for Tumor Diseases (NCT), Heidelberg, for storage and processing of the tissue samples.

Funding

This work was supported by the German Research Council (BR 1704/6-1, BR 1704/6-3, BR 1704/6-4, CH 117/1-1, HO 5117/2-1, HE 5998/2-1, KL 2354/3-1, RO 2270/8-1 and BR 1704/17-1), the German Federal Ministry of Education and Research (01KH0404, 01ER0814, 01ER0815, 01ER1505A and 01ER1505B), and the Interdisciplinary Research Program of the National Center for Tumor Diseases (NCT), Germany.

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Authors and Affiliations

  1. Division of Clinical Epidemiology and Aging Research, German Cancer Research Center (DKFZ), Im Neuenheimer Feld 581, 69120, Heidelberg, Germany

    Prudence R. Carr, Lina Jansen, Stefanie Bienert, Hermann Brenner & Michael Hoffmeister

  2. Institute of Pathology, University Medical Center Mainz, Mainz, Germany

    Wilfried Roth

  3. Institute of Pathology, Heidelberg University Hospital, Heidelberg, Germany

    Wilfried Roth & Esther Herpel

  4. NCT Tissue Bank, National Center for Tumor Diseases (NCT), Heidelberg, Germany

    Esther Herpel

  5. Department of Applied Tumor Biology, Institute of Pathology, Heidelberg University Hospital, Heidelberg, Germany

    Matthias Kloor

  6. Institute of Pathology, Charité University Medicine, Berlin, Germany

    Hendrik Bläker

  7. Division of Cancer Epidemiology, German Cancer Research Center (DKFZ), Heidelberg, Germany

    Jenny Chang-Claude

  8. Genetic Tumour Epidemiology Group, University Medical Center Hamburg-Eppendorf, University Cancer Center Hamburg, Hamburg, Germany

    Jenny Chang-Claude

  9. Division of Preventive Oncology, German Cancer Research Center (DKFZ), Heidelberg, Germany

    Hermann Brenner

  10. German Cancer Consortium (DKTK), German Cancer Research Center (DKFZ), Heidelberg, Germany

    Hermann Brenner

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  1. Prudence R. Carr
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  5. Esther Herpel
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  9. Hermann Brenner
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  10. Michael Hoffmeister
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Correspondence to Michael Hoffmeister.

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All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.

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Informed consent was obtained from all individual participants included in the study.

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Carr, P.R., Jansen, L., Bienert, S. et al. Associations of red and processed meat intake with major molecular pathological features of colorectal cancer. Eur J Epidemiol 32, 409–418 (2017). https://doi.org/10.1007/s10654-017-0275-6

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  • DOI: https://doi.org/10.1007/s10654-017-0275-6

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