Red Meat And Cancer: The Biological Evidence

Two weeks ago, we discussed the link between red meat consumption and breast cancer risk. This relationship is particularly interesting, given that younger women and those taking birth control pills were at the highest risk for breast cancer, indicating some kind of interaction between sex hormones and eating red meat. What wasn’t so well covered is the actual biological explanation for how red meat may contribute to causing cancer.

Current evidence is from large-scale population studies, which actually cannot tell us much about biological mechanisms. The first way these studies are done is through recruiting people who already have cancer, and matching them to similar people without cancer for comparison. Both groups – the cancer ‘cases’ and the healthy ‘controls’ – are asked about their historical consumption of red meat along other dietary and lifestyle factors that may also affect cancer risk. This is called a ‘case-control’ study. The second strategy involves recruiting a large group of healthy people, assessing their red meat consumption and other risk factors in real time, and following them forward in time to see who gets cancer and who doesn’t. This is called a ‘prospective cohort’ study, and provides more scientific validity than a case-control study because it happens in real time.

Both of these epidemiological strategies tell us a lot about population trends. Several, high-quality case-control and prospective cohort studies have consistently found relationships between red and processed meat intake and risks of breast cancer, colorectal cancer, death from cancer and cardiovascular disease, and overall risk of death. These relationships were independent of major dietary and lifestyle risk factors, which were carefully measured and statistically adjusted for (1-5).

There are hypotheses put forward by epidemiologists and biomedical scientists to explain the link between red meat intake and cancer risk:

1. Carcinogenic by-products of cooking meat at high temperatures

img src="http://blogs.plos.org/publichealth/files/2014/11/pah.jpg" alt="pah" width="367" height="341" srcset="https://blogs.plos.org/publichealth/files/2014/11/pah.jpg 408w, https://blogs.plos.org/publichealth/files/2014/11/pah-300x279.jpg 300w" sizes="(max-width: 367px) 100vw, 367px"">pahStructural formulas of some PAHs | ATSDR

When meat is barbequed, grilled, or otherwise cooked at a high temperature, chemical by-products, which have the potential to cause cancer are formed. They are called heterocyclic amines (HCAs) and polycyclic aromatic hydrocarbons (PAHs). Both PAHs and HCAs have been found to be carcinogenic in rodents, but the biological evidence for humans is not yet well established (6).

img src="http://blogs.plos.org/publichealth/files/2014/11/HCA.jpg" alt="HCA" width="270" height="394" srcset="https://blogs.plos.org/publichealth/files/2014/11/HCA.jpg 300w, https://blogs.plos.org/publichealth/files/2014/11/HCA-205x300.jpg 205w" sizes="(max-width: 270px) 100vw, 270px"">HCAThe formation of HCAs during cooking |

Precision Nutrition

HCAs are formed when nutrients in meat – amino acids, sugars, and creatine – react together at high temperatures (6). PAHs are formed when fat and juices from meat drip onto an open flame, causing PAHs from the flame to stick to the surface of the meat (6). PAHs are also found in cigarette smoke and emissions from diesel fuelled-engines, so they are often studied in relation to air pollution (7). They have been linked to breast cancer in epidemiological studies, and this evidence is supported by biomedical research showing that PAHs are stored in the fat tissue of the breast, that they weakly mimic estrogen, and that they bind to DNA, forming damaging PAH-DNA adducts (7-9).

2. Nitrites and nitrates in processed meats

Nitrites and nitrates are found in processed meats, such as bacon, sausages, and hot dogs. In the large intestine, these compounds react with naturally occurring amines in meat to form carcinogenic N-nitroso compounds (NOCs). NOCs have been found to cause cancer in over 40 different animal species (10). Prospective studies have found a link between NOCs and gastrointestinal cancers, including oesophageal, stomach, and colorectal and rectal cancers (11-13). There is some evidence that the antioxidant vitamins C and E could help counteract the effects of NOCs (12,13), but further research is needed.

3. Hormone residues in meat

This explanation is one of the most worrying, as it would be due to growth hormones fed to cattle during farming. There is the least amount of evidence for this hypothesis, and surely there is strong political resistance from the meat industry against this possibility. In many places, use of growth hormones such recombinant bovine growth hormone (rBGH), which is actually more of a concern for dairy products, is banned or has been reduced in its usage. The Huffington Post has an interesting article on this issue.

4. Heme in red meat

The final hypothesis I will cover here is that of heme. Heme is the iron-containing chemical compound in red meat, also providing its pigment or colour. While dietary iron is crucial to good health, heme is also toxic in the digestive system. It has its own toxicity, but also acts to promote the formation of NOCs (14). Population-based cohort studies have found mixed evidence on the relationship between dietary consumption of heme from red meat and cancer incidence (15).

img src="http://blogs.plos.org/publichealth/files/2014/11/gut.jpg" alt="gut" width="300" height="300" srcset="https://blogs.plos.org/publichealth/files/2014/11/gut.jpg 300w, https://blogs.plos.org/publichealth/files/2014/11/gut-150x150.jpg 150w, https://blogs.plos.org/publichealth/files/2014/11/gut-100x100.jpg 100w, https://blogs.plos.org/publichealth/files/2014/11/gut-70x70.jpg 70w, https://blogs.plos.org/publichealth/files/2014/11/gut-60x60.jpg 60w, https://blogs.plos.org/publichealth/files/2014/11/gut-32x32.jpg 32w, https://blogs.plos.org/publichealth/files/2014/11/gut-64x64.jpg 64w, https://blogs.plos.org/publichealth/files/2014/11/gut-96x96.jpg 96w, https://blogs.plos.org/publichealth/files/2014/11/gut-128x128.jpg 128w" sizes="(max-width: 300px) 100vw, 300px"">gutThe curiosity of the human gut microbiome | CR Way

Another current question is the role of genetics in how red meats are metabolised, and whether genetic differences may make some people more susceptible than others to any potential effects of eating red meat (16,17). An even newer and dynamic avenue of research is how the gut microbiome interacts with foods to produce health conditions (18). It also may be as simple as people who eat excessive amounts of red meat are probably not eating enough of other healthy foods that might help prevent cancer.

A lesson learned here is that science moves forward incrementally. Although the epidemiological evidence shows strong trends, not all of it is in perfect agreement. There is always some degree of human error present in the practice of research (19), which might obscure the truth. And, as we learn more, we also learn how much we don’t know. There are probably variations in metabolic genes and the gut microbiome within human populations that we don’t even know about yet, not to mention the biological and chemical factors in meat itself. Years from now, we may look back on today’s research as clunky and unrefined, unable to pick up more subtle aspects of the diet-cancer relationship.

In any case, the editors of the journal JAMA Internal Medicine have advocated that “Reducing meat consumption has multiple benefits for the world’s health” (20), a bold statement that future research will tell us more about.

 

References

1)Farvid MS, Cho E, Chen WY, Eliassen AH, Willett WC. Dietary protein sources in early adulthood and breast cancer incidence: prospective cohort study. BMJ 2014;348:g3437

2)Farvid MS, Cho E, Chen WY, Eliassen AH, Willett WC. Adolescent meat intake and breast cancer risk. Int J Cancer 2014; Published Online First 15 September 2014: doi: 10.1002/ijc.29218

3)Norat T, Bingham S, Ferrari P, Slimani N, Jenab M, Mazuir M, et al. Meat, fish, and colorectal cancer risk: the European Prospective Investigation into Cancer and Nutrition. J Natl Cancer Inst 2005;97(12):906-16.

4)Pan A, Sun Q, Bernstein AM, Schulze MB, Manson JE, Stampfer MJ, et al. Red meat consumption and mortality: results from 2 prospective cohort studies. JAMA Intern Med 2012;172(7):555-63.

5)Sinha R, Cross AJ, Graubard BI, Leitzmann MF, Schatzkin A. Meat intake and mortality: a prospective study of over half a million people. JAMA Intern Med 2009;169(6):562-71.

6)National Cancer Institute. Chemicals in meat cooked and high temperatures and cancer risk. http://www.cancer.gov/cancertopics/factsheet/Risk/cooked-meats (accessed 16 November 2014).

7)Breast Cancer Fund. Polycyclic aromatic hydrocarbons (PAHs).  http://www.breastcancerfund.org/clear-science/radiation-chemicals-and-breast-cancer/polycyclic-aromatic-hydrocarbons.html (accessed 17 November 2014).

8)Rundle A, Tang D, Hibshoosh H, Estabrook A, Schnabel F, Cao W, et al. The relationship between genetic damage from polycyclic aromatic hydrocarbons in breast tissue and breast cancer. Carcinogenesis 2000;21(7):1281-9.

9)Gammon MD, Santella RM, Neuget AI, Eng SM, Teitelbaum SL, Paykin A, et al. Environmental toxins and breast cancer on Long Island. I. Polycyclic aromatic hydrocarbon DNA adducts. Cancer Epidemiol Biomarkers Prev  2002;11:677-85.

10)Bogovski P, Bogovski S. Animal species in which N-nitroso compounds induce cancer. Int J Cancer 1981;27:471-4.

11)Jakszyn P, Gonzalez CA, Nitrosamine and related food intake and gastric and oesophageal cancer risk: a systematic review of the epidemiological evidence. World J Gastroenterol 2006;12(27):4296-303.

12)Zhu Y, Wang PP, Zhao J, Green R, Sun Z, Roebothan B, et al. Dietary N-nitroso compounds and risk of colorectal cancer: a case-control study in Newfoundland and Laborador and Ontario, Canada. Br J Nutr 2014;111(6):1109-17.

13)Loh YH, Jakszyn P, Luben RN, Mulligan AA, Mitrou PN, Khaw KT. N-nitroso compounds and cancer incidence: the European Prospective Investigation into Cancer and Nutrition (EPIC)-Norfolk study. Am J Clin Nutr 2011;93(5):1053-61.

14)Bastide NM, Pierre FH, Corpet DE. Heme iron from red meat and risk of colorectal cancer: a meta-analysis and a review of the mechanisms involved. Cancer Prev Res 2011;4(2):177-84.

15)Kim E, Coelho D, Blachier F. Review of the association between meat consumption and risk of colorectal cancer. Nutr Res 2013;33:983-94.

16)Ananthakrishnan AN, Du M, Berndt SI, Brenner H, Caan BJ, Casey G, et al. Red meat intake, NAT2, and risk of colorectal cancer: a pooled analysis of 11 studies. Cancer Epidemiol Biomarkers Prev 2014 (in press).

17)Ho V, Peacock S, Massey TE, Ashbury JE, Vanner SJ, King WD. Meat-derived carcinogens, genetic susceptibility, and colorectal adenoma risk. Genes Nutr 2014;9(6):430.

18)Feltman R. The gut’s microbiome changes rapidly with diet. Scientific American. 14 December 213. http://www.scientificamerican.com/article/the-guts-microbiome-changes-diet/ (accessed 17 November 2014).

19)Ioannidis JPA. Why most published research findings are false. PLOS Med 2005;2(8):e124.

20)Popkin BM. Reducing meat consumption has multiple benefits for the world’s health. JAMA Intern Med 2009;169(6):543-5.

Image source: Gizmodo

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Source : https://blogs.plos.org/publichealth/2014/11/17/red-meat-biological-evidence/

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