In October, 2015, 22 scientists from ten countries met at
the International Agency for Research on Cancer (IARC) in Lyon, France,
to evaluate the carcinogenicity of the consumption of red meat and
processed meat. These assessments will be published in volume 114 of the
IARC Monographs.1
Red
meat refers to unprocessed mammalian muscle meat—for example, beef,
veal, pork, lamb, mutton, horse, or goat meat—including minced or frozen
meat; it is usually consumed cooked. Processed meat refers to meat that
has been transformed through salting, curing, fermentation, smoking, or
other processes to enhance flavour or improve preservation. Most
processed meats contain pork or beef, but might also contain other red
meats, poultry, offal (eg, liver), or meat byproducts such as blood.
Red
meat contains high biological-value proteins and important
micronutrients such as B vitamins, iron (both free iron and haem iron),
and zinc. The fat content of red meat varies depending on animal
species, age, sex, breed, and feed, and the cut of the meat. Meat
processing, such as curing and smoking, can result in formation of
carcinogenic chemicals, including N-nitroso-compounds (NOC) and
polycyclic aromatic hydrocarbons (PAH). Cooking improves the
digestibility and palatability of meat, but can also produce known or
suspected carcinogens, including heterocyclic aromatic amines (HAA) and
PAH. High-temperature cooking by pan-frying, grilling, or barbecuing
generally produces the highest amounts of these chemicals.2, 3
Depending
on the country, the proportion of the population that consumes red meat
varies worldwide from less than 5% to up to 100%, and from less than 2%
to 65% for processed meat. The mean intake of red meat by those who
consume it is about 50–100 g per person per day, with high consumption
equalling more than 200 g per person per day.4 Less information is available on the consumption of processed meat.
The
Working Group assessed more than 800 epidemiological studies that
investigated the association of cancer with consumption of red meat or
processed meat in many countries, from several continents, with diverse
ethnicities and diets. For the evaluation, the greatest weight was given
to prospective cohort studies done in the general population. High
quality population-based case-control studies provided additional
evidence. For both designs, the studies judged to be most informative
were those that considered red meat and processed meat separately, had
quantitative dietary data obtained from validated questionnaires, a
large sample size, and controlled for the major potential confounders
for the cancer sites concerned.
The largest body of
epidemiological data concerned colorectal cancer. Data on the
association of red meat consumption with colorectal cancer were
available from 14 cohort studies. Positive associations were seen with
high versus low consumption of red meat in half of those studies,
including a cohort from ten European countries spanning a wide range of
meat consumption and other large cohorts in Sweden and Australia.5, 6, 7
Of the 15 informative case-control studies considered, seven reported
positive associations of colorectal cancer with high versus low
consumption of red meat. Positive associations of colorectal cancer with
consumption of processed meat were reported in 12 of the 18 cohort
studies that provided relevant data, including studies in Europe, Japan,
and the USA.5, 8, 9, 10, 11
Supporting evidence came from six of nine informative case-control
studies. A meta-analysis of colorectal cancer in ten cohort studies
reported a statistically significant dose–response relationship, with a
17% increased risk (95% CI 1·05–1·31) per 100 g per day of red meat and
an 18% increase (95% CI 1·10–1·28) per 50 g per day of processed meat.12
Data
were also available for more than 15 other types of cancer. Positive
associations were seen in cohort studies and population-based
case-control studies between consumption of red meat and cancers of the
pancreas and the prostate (mainly advanced prostate cancer), and between
consumption of processed meat and cancer of the stomach.
On
the basis of the large amount of data and the consistent associations
of colorectal cancer with consumption of processed meat across studies
in different populations, which make chance, bias, and confounding
unlikely as explanations, a majority of the Working Group concluded that
there is sufficient evidence in human beings for the carcinogenicity of
the consumption of processed meat. Chance, bias, and confounding could
not be ruled out with the same degree of confidence for the data on red
meat consumption, since no clear association was seen in several of the
high quality studies and residual confounding from other diet and
lifestyle risk is difficult to exclude. The Working Group concluded that
there is limited evidence in human beings for the carcinogenicity of
the consumption of red meat.
There is inadequate evidence
in experimental animals for the carcinogenicity of consumption of red
meat and of processed meat. In rats treated with colon cancer initiators
and promoted with low calcium diets containing either red meat or
processed meat, an increase in the occurrence of colonic preneoplastic
lesions was reported in three and four studies, respectively.13, 14, 15
The
mechanistic evidence for carcinogenicity was assessed as strong for red
meat and moderate for processed meat. Mechanistic evidence is mainly
available for the digestive tract. A meta-analysis published in 2013
reported a modest but statistically significant association between
consumption of red or processed meat and adenomas (preneoplastic
lesions) of the colorectum that was consistent across studies.16
For genotoxicity and oxidative stress, evidence was moderate for the
consumption of red or processed meat. In human beings, observational
data showed slight but statistically significant associations with APC
gene mutation or promoter methylation that were identified in 75 (43%)
and 41 (23%) of 185 archival colorectal cancer samples, respectively.17
Consuming well done cooked red meat increases the bacterial
mutagenicity of human urine. In three intervention studies in human
beings, changes in oxidative stress markers (either in urine, faeces, or
blood) were associated with consumption of red meat or processed meat.18 Red and processed meat intake increased lipid oxidation products in rodent faeces.13
Substantial
supporting mechanistic evidence was available for multiple meat
components (NOC, haem iron, and HAA). Consumption of red meat and
processed meat by man induces NOC formation in the colon. High red meat
consumption (300 or 420 g/day) increased levels of DNA adducts
putatively derived from NOC in exfoliated colonocytes or rectal biopsies
in two intervention studies.19, 20
Few human data, especially from intervention studies, were available
for processed meat. Haem iron mediates formation of NOC, and of lipid
oxidation products in the digestive tract of human beings and rodents.
Haem iron effects can be experimentally suppressed by calcium,
supporting its contribution to carcinogenic mechanisms. Meat heated at a
high temperature contains HAA. HAA are genotoxic, and the extent of
conversion of HAA to genotoxic metabolites is greater in man than in
rodents. Meat smoked or cooked over a heated surface or open flame
contains PAH. These chemicals cause DNA damage, but little direct
evidence exists that this occurs following meat consumption.
Overall,
the Working Group classified consumption of processed meat as
“carcinogenic to humans” (Group 1) on the basis of sufficient evidence
for colorectal cancer. Additionally, a positive association with the
consumption of processed meat was found for stomach cancer.
The
Working Group classified consumption of red meat as “probably
carcinogenic to humans” (Group 2A). In making this evaluation, the
Working Group took into consideration all the relevant data, including
the substantial epidemiological data showing a positive association
between consumption of red meat and colorectal cancer and the strong
mechanistic evidence. Consumption of red meat was also positively
associated with pancreatic and with prostate cancer.
For more on the IARC Monographs see http://monographs.iarc.fr/
Upcoming meetings Feb 2–9, 2016, Volume 115: Some industrial chemicals; May 24–31, 2016, Volume 116: Coffee and some other hot beverages
IARC Monograph Working Group Members
B W Stewart (Australia)—meeting chair; S De Smet (Belgium); D Corpet, M
Meurillon (France); G Caderni (Italy); S Rohrmann; P Verger
(Switzerland); S Sasazuki, K Wakabayashi (Japan); M P Weijenberg
(Netherlands); A Wolk (Sweden); M Cantwell; T Norat; P Vineis (UK); F A
Beland, E Cho, D M Klurfeld, L Le Marchand, R Sinha, M Stern, R Turesky,
K Wu (USA)
Declaration of interests TN was
involved in a research project funded by the World Cancer Research Fund,
a registered charity. All other working group members declare no
competing interests.
Invited Specialists None
Representatives
A Christodoulidou, for the European Food Safety Authority (EFSA),
Italy; I Margaritis, for the French Agency for Food, Environment and
Occupational Health and Safety (ANSES), France; Y Totsuka, for the
National Cancer Center Research Institute, Japan
Declaration of interests All representatives declare no competing interests.
Observers
D D Alexander, for the EpidStat Institute, USA; B L Booren, for the
North American Meat Institute, USA; J Carretier, for the Léon Bérard
Centre, France; J J Hlywka, for the Kraft Heinz Company, USA; D A
Kovich, for the National Pork Producers Council, USA; H J Lazaneo, for
the National Meat Institute (INAC), Uruguay; M McCullough, for the
American Cancer Society, USA; S McNeill, for Beef Checkoff, USA
Declaration of interests
DDA has received consulting fees from Beef Checkoff for research on red
meat and cancer. BLB receives a salary from the North American Meat
Institute (NAMI) and the North American Meat Institute Foundation
(NAMIF). BLB publicly represents in media, government, and scientific
meetings, among others, the NAMI and NAMIF position and analysis of
scientific evidence. DAK is employed by the National Pork Producers
Council, USA. SMcN is an employee of the National Cattlemen's Beef
Association and is a contractor to the Beef Checkoff. All other
observers declare no competing interests.
IARC/WHO Secretariat
L Benbrahim-Tallaa; V Bouvard; F El Ghissassi; C Espina; E Feletto; J
Gomes; Y Grosse; N Guha; K Z Guyton; I Huybrechts; D Loomis; H Mattock; A
Mullee; I Romieu; C Santamaria-Ulloa; M Stepien; K Straif
Declaration of interests All secretariat declare no competing interests.
For the Preamble to the IARC Monographs see http://monographs.iarc.fr/ENG/Preamble/index.php
For IARC declarations of interests see http://monographs.iarc.fr/ENG/Meetings/vol.114-participants/