Processed meats and cancer Mariana C. Stern, PhD Associate Professor of Preventive Medicine & Urology USC Norris Comprehensive Cancer Center July 29, 2016 International Conference on Nutrition in Medicine
October 2015
Frequent questions Is it really that bad? Scientist say this today and tomorrow they will say it is good for us! We should ignore it We all have to die of something.
Systematic Reviews Meta-analyses Cohort studies Case-control studies Cross-sectional studies Ecological studies
Systematic Reviews Among people diagnosed with cancer, is the Meta-analyses average meat intake higher than among people cancerfree? Cohort studies Case-control studies Cross-sectional studies Ecological studies
Systematic Reviews How likely are people who eat a lot of meat to get cancer compared to those who eat little or no meat? Meta-analyses Cohort studies Case-control studies Cross-sectional studies Ecological studies
Do findings agree? What is the average estimate of effect across studies? Systematic Reviews Meta-analyses Cohort studies Case-control studies Cross-sectional studies Ecological studies
Are there mechanisms that explain this? Are some individuals more susceptible? Which are the gaps of knowledge? Systematic Reviews Meta-analyses Are there geographical patterns? Cohort studies Case-control studies Cross-sectional studies Ecological studies
Systematic review by the World Cancer Research Fund WCRF/AICR In 2011 WCRF reported red meat and processed meat are conclusive risk factors for colorectal cancer The role of RM and PM in other cancers was inconclusive but suggestive for many cancers
WORLD HEALTH ORGANIZATION INTERNATIONAL AGENCY FOR RESEARCH ON CANCER IARC Monographs on the Evaluation of Carcinogenic Risks to Humans GOAL: IARC Monograph Identify Evaluations environmental agents that can increase the risk of human cancer. AGENTS: Chemicals, complex mixtures, occupational exposures, physical agents, biological agents, and lifestyle factors. UTILITY: National health agencies can use this information as scientific support for their actions to prevent exposure to potential LYON, FRANCE carcinogens.
IARC monographs Since 1971, more than 900 agents have been studied ~400 have been found to be carcinogenic Tobacco smoke, asbestos, outdoor air pollution, salted fish, being a painter, alcoholic drinks Most comprehensive assessment of carcinogenic exposures Human epidemiological studies Animal studies Mechanistic studies No paper left behind approach..
Talk Roadmap Process & findings Interpretation Recommendations
Agent definition Red meat: mammalian muscle meat, including, beef, veal, pork, lamb, mutton, horse, goat Processed meat: meat that has been transformed through salting, curing, fermentation, smoking, or other processes to enhance flavor or improve preservation. They may contain red meats, poultry, offal, or meat by products such as blood.
Literature included ALL existing papers were reviewed Inclusion criteria applied for subset that contributed to evaluation Clear definition of red meat and processed meat Sample size > 100 cases Estimates of association reported
Most influential studies Cohort studies were given priority Case-control studies used for support Population-based studies vs. hospital-based studies Large sample size Used a validated food frequency questionnaire Adequate adjustment of confounders
Colorectal cancer Main cancer associated with red meat and processed meats ~20 cohort studies (multiple papers) 144 total papers from case-control studies
Red and Processed Meat and Colorectal Cancer Unprocessed Red Meat & Colorectal Cancer Cohort Studies Chan, 2011. Plos One
Unprocessed Red Read Meat & Meat Colorectal CRC Cancer Case-Control Case-control Studies Study ID RR (95% CI) % Weight CRC Boutron-Ruault (Beef) 1999 Le Marchand 2001 Navarro (red meat) 2003 Barrett 2003 Juarranz Sanz 2004 Kimura 2007 Rosato 2013 Miller 2013 Joshi 2015 Steinmetz (M) 1993 Steinmetz (F) 1993 Le Marchand (F) 1997 Le Marchand (M) 1997 Subtotal (I-squared = 76.8%, p = 0.000). rectum Murthaugh (M) 2004 Gerhardsson - boiled 1991 Miller 2013 Joshi 2015 Subtotal (I-squared = 22.9%, p = 0.274). colon Chiu (F) 2003 Chiu (M) 2003 Kimura -Distal 2007 Kimura - Proximal 2007 Gerhardsson- fried 1991 Miller - Proximal 2013 Joshi 2015 Kampman (M) 1999 Kampman (F) 1999 Subtotal (I-squared = 0.0%, p = 0.501). NOTE: Weights are from random effects analysis 1.40 (0.81, 2.42) 1.00 (0.71, 1.41) 0.63 (0.51, 0.78) 1.97 (1.30, 2.98) 1.03 (1.02, 1.05) 1.13 (0.80, 1.60) 1.07 (0.78, 1.46) 1.02 (0.75, 1.39) 1.20 (1.01, 1.42) 1.59 (0.81, 3.13) 1.48 (0.73, 3.01) 1.30 (0.85, 1.99) 2.10 (1.41, 3.12) 1.16 (1.00, 1.35) 1.10 (0.79, 1.54) 1.90 (1.20, 3.00) 1.20 (0.75, 1.92) 1.20 (0.93, 1.55) 1.27 (1.03, 1.55) 1.50 (1.01, 2.22) 1.50 (1.04, 2.17) 1.23 (0.75, 2.01) 1.44 (0.76, 2.72) 1.10 (0.69, 1.76) 1.09 (0.72, 1.65) 1.20 (0.96, 1.50) 0.90 (0.66, 1.23) 1.00 (0.68, 1.46) 1.17 (1.04, 1.32) 4.79 7.82 10.69 6.62 13.44 7.76 8.53 8.49 11.50 3.60 3.36 6.48 6.91 100.00 27.29 16.71 16.09 39.91 100.00 9.40 10.62 6.07 3.62 6.55 8.50 29.93 15.25 10.06 100.00.1.2.5 1 2 5 10 Relative Risk Estimate IARC monographs vol 114 Working Group
Red and Processed Meat and Colorectal Cancer Processed Meat & Colorectal Cancer Cohort Studies Figure 5. Dose-response meta-analyses of processed meat consumpt ion and the risk of colorectal, colon and rectal cancers. Chan, 2011. Plos One
Processed Meat Read & Colorectal Meat CRC Cancer Case-Control Case-control Studies Study ID RR (95% CI) % Weight CRC Boutron-Ruault - Deli 1999 Navarro 2003 Juarranz Sanz 2004 Kimura 2007 Rosato 2013 Miller 2013 Joshi 2015 Steinmetz (M) 1993 Steinmetz (F) 1993 Le Marchand (M) 1997 Le Marchand (F) 1997 Subtotal (I-squared = 64.5%, p = 0.002). rectum Boutron-Ruault - Deli 1999 Murthaugh (F) 2004 Murthaugh (M) 2004 Kimura 2007 Gerhardsson (fried) 1991 Williams (White) 2010 Williams (AA) 2010 Hu J 2011 Joshi 2015 Subtotal (I-squared = 4.3%, p = 0.399). colon Hu J 2011 Miller 2013 Joshi 2015 Subtotal (I-squared = 23.9%, p = 0.269). NOTE: Weights are from random effects analysis 2.40 (1.29, 4.47) 4.35 1.47 (1.01, 2.13) 8.68 1.07 (1.04, 1.11) 19.58 1.15 (0.83, 1.60) 9.94 1.56 (1.11, 2.20) 9.53 1.18 (0.86, 1.61) 10.48 1.10 (0.93, 1.30) 15.70 1.03 (0.55, 1.94) 4.23 0.77 (0.35, 1.69) 2.97 2.30 (1.53, 3.46) 7.79 1.20 (0.76, 1.90) 6.75 1.28 (1.10, 1.48) 100.00 2.20 (1.00, 4.82) 2.57 1.23 (0.84, 1.81) 10.41 1.18 (0.87, 1.61) 15.82 1.14 (0.73, 1.78) 7.90 1.50 (0.98, 2.29) 8.61 1.16 (0.80, 1.68) 11.11 0.86 (0.38, 1.95) 2.36 1.50 (1.16, 1.94) 22.33 1.00 (0.76, 1.32) 18.89 1.24 (1.09, 1.41) 100.00 1.50 (1.22, 1.84) 40.99 1.21 (0.86, 1.70) 18.02 1.20 (0.98, 1.47) 40.99 1.32 (1.13, 1.54) 100.00.1.2.5 1 2 5 10 Relative Risk Estimate IARC monographs vol 114 Working Group
Evaluation of evidence Sufficient evidence of carcinogenicity Limited evidence of carcinogenicity Inadequate evidence of carcinogenicity Evidence suggesting lack of carcinogenicity
Evaluation of evidence Sufficient evidence of carcinogenicity Positive association observed, other explanations or noise can be ruled out with reasonable confidence a causal relationship can be inferred Limited evidence of carcinogenicity Inadequate evidence of carcinogenicity Evidence suggesting lack of carcinogenicity
Evaluation of evidence Sufficient evidence of carcinogenicity Limited evidence of carcinogenicity Positive association observed, but other explanations or study noise cannot be ruled out with reasonable confidence Inadequate evidence of carcinogenicity Evidence suggesting lack of carcinogenicity
Evaluation of evidence Sufficient evidence of carcinogenicity Limited evidence of carcinogenicity Inadequate evidence of carcinogenicity The available studies are of insufficient quality, consistency or statistical power to draw final conclusions, or no data on cancer in humans are available. Evidence suggesting lack of carcinogenicity
Evaluation of evidence Sufficient evidence of carcinogenicity Limited evidence of carcinogenicity Inadequate evidence of carcinogenicity Evidence suggesting lack of carcinogenicity Adequate number of studies showing lack of associations consistency, and other explanations or study problems can be ruled out with reasonable confidence
IARC classification of agents
Processed meats
Red meat 2A 2B Mechanistic group EVIDENCE WAS STRONG UPGRADE 2B TO 2A
Classification Group 1 Causes Cancer Group 2A Probably Causes Cancer
Evidence by cancers Red meat Limited evidence: colorectal, pancreas, prostate Inadequate evidence: breast, stomach, liver, kidney, NHL, leukemias, lung, esophagus Processed meat Sufficient evidence: colorectal Limited evidence: stomach Inadequate evidence: breast, liver, kidney, NHL, leukemias, lung, esophagus, pancreas, prostate
Is processed meat as bad as smoking???
Processed meats and tobacco are in the same group based on the strength of the evidence However, the level of risk is different! ~49,700 cancer cases could be prevented in the US if no-one eat any processed meats
Which are the mechanisms? Nitrate salts Heme iron Heterocylic amines Polyclic aromatic hydrocarbons Advanced glycation end-products N-glycolylneuraminic acid (Neu5Gc) STRONG EVIDENCE
Proposed mechanism 1: NOCs DNA DAMAGE
Endogenous formation of NOCs Cross et al., 2003, Cancer Research
Proposed mechanism 2: Heme iron MYOGLOBIN determined the redness of meat HEME IRON in nitrite cured meat is mostly nitrosylated
How does heme iron contribute to carcinogenesis Aids in the formation of NOCs endogenously Catalyzes the oxidation of polyunsaturated fats lipid peroxidation products Heme may damage the colonic mucosa directly, causing proliferation and DNA damage
Proposed mechanism 3 High temperature cooking methods lead to the formation of HETEROCYCLIC AMINES which can lead to DNA damage and cancer formation
Big Mac 3.2 oz Recommendations: 500 grams per week (~18 oz) In-N-out 2 oz 71 grams per day (~2.5 oz) Most should be fresh 3 oz
Vegetables come first
Give plant-based sources of protein a chance
What next? More research on mechanisms Better understanding of the relevant window of exposure More research on other cancers and multi-ethnic populations
Processed meat and breast cancer among Latinas ~4,000 Latinas & ~4,000 NLW women California, Utah, Colorado, New Mexico, Arizona Diets high in processed meats were associated with ~40% increase of breast cancer risk among Latinas, not NLW! Both pre- and post-menopausal Stronger for ER+ women Timing of exposure? Kim et al. Cancer Causes and Control, 2016
Thank you! Questions? marianas@usc.edu Twitter @MarianaStern