Does red meat cause cancer?

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On a population wide basis, red meat is definitely associated with cancer. The association has been shown numerous times, but is fairly weak in relevance. The most well-controlled study noted an 0.2-fold increase.

Please note association; this has not yet been shown through interventions nor is the cause known. If we are to answer 'does red meat cause cancer', the answer is 'we do not know'

Epidemiology

Recently, a study published controlled for other dietary confounders as well as activity and the basics (smoking, alcohol, social class) and found a Hazard Ratio of 1.16 (+16% risk) for red meat and cancer.[1] Past studies of the same manner find Hazard ratios around 1.2 as well,[2] although this latter study was criticized for its controls.[3] It should be noted that the 20% increased risk was derived from comparing the top quintile (20%) against the bottom quintile of meat consumption, and means a 0.2-fold increase.

A select few studies look at risk of cancer in general, whereas others look at specific forms of cancer. This is due to red meat intake being weakly but confidently associated with various forms of cancer.[4]

A netherlands cohort found an association with a hazard ratio of 2.66 for unprocessed red meat and 3.47 in regards to esophageal squamous cell carcinoma risk in men.[5] No association was found with gastric cancers or esophageal adenocarcinoma, nor esophageal squamous cell carcinoma risk in women.

Colorectal cancer risk is associated with inactivity and low plant consumption[6]

Some studies that measure fiber intake do not find a strong association with distal colorectal cancer risk and red meat.[7]

Interestingly, chicken skin and eggs have been found to confer more risk than lean meats (in a population of Hawaiins), although the strongest correlation was found with total caloric intake.[8] The Relative Risk ratios tended to not exceed 2.0 overall however.

Difference between processed and unprocessed?

Many studies define 'processed' red meats as those that have had added nitrates, due to the correlation between nitrates in meats and nitrosamine formation in the body.

These meats tend to refer to sausages and hot dogs, bacon and other pink meat such as ham, cold cuts, and croquettes.

Compounding and Contributing factors

Risk of colorectal cancer from red meat rises to an 8.8-fold risk when the subject also smokes, and may be due to carcinogens found in the meats as measured by a preference for well-done meat (higher source of the carcinogens Heterocyclic Amines and Polyaromatic Hydrocarbons).[9]

In persons with overactive NAT1/NAT2 enzymes, there is an increased risk of colorectal cancer from meats.[10][11] This may be due to rapid bioactivation of Heterocyclic Amines, which are known colonic carcinogens. One study noted that this phenotype did not associated with an increased cancer risk (OR=1.43) until HCA intake was measured (OR=6.50); those without the phenotype had a lesser increase in risk (OR=2.32).[12] Other P450 enzymes may also contribute to a lesser extent.[13]

In studies that measure HCAs, they correlate similarly if not better with cancer than red meat does itself.[14][15][16]

As NAT1/NAT2 enzymes metabolize caffeine only after CYP1A, a caffeine tolerance test can be used to assess personal susceptibility to HCA-induced carcinogenesis risk via CYP1A.[17] This has been used in some studies[9] and, informally, might be a good indicator of risk if taken with some skepticism (with more caffeine tolerance correlating with more risk).

Compounding factors tend to be unhealthy habits like smoking and alcohol; things that are either pro-oxidant in nature or interact with liver enzymes

Standard correlations

Many studies note that people who consume more red meat also tend to consume more energy overall and have a higher BMI, eat less fruits and vegetables, and have higher rates of smoking and alcohol consumption with a slightly lower education level.[5][1] Socioeconomic class has also been related to red meat and mortality (lower socioeconomic classes eat more red meat) but this does not seem to fully explain the link either.[18] Exercise is also a factor to be considered, specifically cardiorespiratory fitness, as an indicator of diet.[19]

If not otherwise controlled for, these common confounders can influence the results of survey research.

Causation or Causes?

As there have been no interventions, it cannot be concluded that red meat causes cancer or mortality. It is associated, but causation has not yet been established.

If it were to cause cancer or increased mortality, suspect areas could be as follows.

Meat mutagens

Various compounds produced in meats during cooking and processing have possible pro-carcinogenic effects when consumed by humans. T

The content of HCAs and PAHs are more indicative of preparation method than of meat selected, and tend to be associated with preparation methods of red meats rather than chicken or fish (barbecuing, flame grilling). Nitrosamines tend to be associated with pink meats such as ham or bacon, although their levels are even higher in fermented fish products.

Prevention Techniques?

In all studies that controlled for vegetable intake, a greater risk was seen in people not consuming vegetables. On a whole, vegetable intake seems to confer a protective effect.[1][5] In addition, one research group noted that although red meat causes increases in a variety of cancers[4] that fruits and veggies seemed to confer protective effects against just as wide a variety, and were more protective in cohorts that were more at risk.[20] Fruits appeared to be more protective than vegetables in this study.

References
1.^Pan A, Sun Q, Bernstein AM, Schulze MB, Manson JE, Stampfer MJ, Willett WC, Hu FBRed Meat Consumption and Mortality: Results From 2 Prospective Cohort StudiesArch Intern Med.(2012 Mar 12)
2.^Sinha R, Cross AJ, Graubard BI, Leitzmann MF, Schatzkin AMeat intake and mortality: a prospective study of over half a million peopleArch Intern Med.(2009 Mar 23)
4.^Aune D, De Stefani E, Ronco A, Boffetta P, Deneo-Pellegrini H, Acosta G, Mendilaharsu MMeat consumption and cancer risk: a case-control study in UruguayAsian Pac J Cancer Prev.(2009 Jul-Sep)
6.^Arafa MA, Waly MI, Jriesat S, Al Khafajei A, Sallam SDietary and lifestyle characteristics of colorectal cancer in Jordan: a case-control studyAsian Pac J Cancer Prev.(2011)
7.^Williams CD, Satia JA, Adair LS, Stevens J, Galanko J, Keku TO, Sandler RSAssociations of red meat, fat, and protein intake with distal colorectal cancer riskNutr Cancer.(2010)
9.^Le Marchand L, Hankin JH, Pierce LM, Sinha R, Nerurkar PV, Franke AA, Wilkens LR, Kolonel LN, Donlon T, Seifried A, Custer LJ, Lum-Jones A, Chang WWell-done red meat, metabolic phenotypes and colorectal cancer in HawaiiMutat Res.(2002 Sep 30)
10.^Roberts-Thomson IC, Butler WJ, Ryan PMeat, metabolic genotypes and risk for colorectal cancerEur J Cancer Prev.(1999 Jul)
11.^Yeh CC, Sung FC, Tang R, Chang-Chieh CR, Hsieh LLPolymorphisms of cytochrome P450 1A2 and N-acetyltransferase genes, meat consumption, and risk of colorectal cancerDis Colon Rectum.(2009 Jan)
12.^Ishibe N, Sinha R, Hein DW, Kulldorff M, Strickland P, Fretland AJ, Chow WH, Kadlubar FF, Lang NP, Rothman NGenetic polymorphisms in heterocyclic amine metabolism and risk of colorectal adenomasPharmacogenetics.(2002 Mar)
13.^Yoshida K, Osawa K, Kasahara M, Miyaishi A, Nakanishi K, Hayamizu S, Osawa Y, Tsutou A, Tabuchi Y, Shimada E, Tanaka K, Yamamoto M, Takahashi JAssociation of CYP1A1, CYP1A2, GSTM1 and NAT2 gene polymorphisms with colorectal cancer and smokingAsian Pac J Cancer Prev.(2007 Jul-Sep)
14.^Lin J, Forman MR, Wang J, Grossman HB, Chen M, Dinney CP, Hawk ET, Wu XIntake of red meat and heterocyclic amines, metabolic pathway genes and bladder cancer riskInt J Cancer.(2012 Jan 19)
15.^Lam TK, Cross AJ, Consonni D, Randi G, Bagnardi V, Bertazzi PA, Caporaso NE, Sinha R, Subar AF, Landi MTIntakes of red meat, processed meat, and meat mutagens increase lung cancer riskCancer Res.(2009 Feb 1)
16.^De Stefani E, Boffetta P, Deneo-Pellegrini H, Ronco AL, Aune D, Acosta G, Brennan P, Mendilaharsu M, Ferro GMeat intake, meat mutagens and risk of lung cancer in Uruguayan menCancer Causes Control.(2009 Nov)
17.^Lang NP, Butler MA, Massengill J, Lawson M, Stotts RC, Hauer-Jensen M, Kadlubar FFRapid metabolic phenotypes for acetyltransferase and cytochrome P4501A2 and putative exposure to food-borne heterocyclic amines increase the risk for colorectal cancer or polypsCancer Epidemiol Biomarkers Prev.(1994 Dec)
18.^Major JM, Cross AJ, Doubeni CA, Park Y, Lian M, Hollenbeck AR, Schatzkin A, Graubard BI, Sinha RSocioeconomic deprivation impact on meat intake and mortality: NIH-AARP Diet and Health StudyCancer Causes Control.(2011 Dec)
19.^Héroux M, Janssen I, Lam M, Lee DC, Hebert JR, Sui X, Blair SNDietary patterns and the risk of mortality: impact of cardiorespiratory fitnessInt J Epidemiol.(2010 Feb)
20.^Aune D, De Stefani E, Ronco A, Boffetta P, Deneo-Pellegrini H, Acosta G, Mendilaharsu MFruits, vegetables and the risk of cancer: a multisite case-control study in UruguayAsian Pac J Cancer Prev.(2009 Jul-Sep)