In a 1979 edition of the American Journal of Epidemiology, Graham and Mettlin (1) reported that the ‘animal fat hypothesis’ was introduced by Ernst Wynder at a 1965 symposium on the aetiology of cancer in the gastrointestinal tract. During the symposium, country-specific age-adjusted mortality rates for colon cancer were shown to increase with increasing per capita animal fat consumption, based on international data (1). Subsequently, the animal fat hypothesis evolved into the hypothesis that meat intake may be associated with increasing the risk of certain types of cancer, although analytical epidemiologic evidence was lacking. In a 1975 ecologic study by Armstrong and Doll (2), published in the International Journal of Cancer, worldwide per capita animal protein consumption rates were strongly correlated with incidence and mortality rates of colon cancer and rectal cancer among men and women. However, in another early ecologic study, no correlation between beef consumption (prior to 1970) and age-adjusted colorectal cancer incidence and mortality rates were observed based on data from the US Department of Agriculture (3). The early hypothesis-generating studies gave way to more advanced and scientifically rigorous designs, such as analytical epidemiologic case–control and prospective cohort studies. To date, despite more than 50 epidemiologic studies of red meat and colorectal cancer over the past few decades, including over 30 prospective studies published in the past 20 years, the potential relationship between red meat consumption and colorectal cancer is equivocal.
Several postulated mechanisms regarding meat consumption and cancer have been examined, although findings from human studies have been relatively inconsistent. Mechanisms involving dietary mutagens (e.g. heterocyclic amines, polycyclic aromatic hydrocarbons), chemical compounds that are not naturally present in foods but may develop during cooking, have been the most heavily studied, but associations from epidemiologic analyses have been variable across several specific compounds (4–8). Other mechanisms involve the potential role of nitrate and nitrite, commonly used in processed meats for preservation agents, and N-nitroso compounds, which have been shown to be carcinogenic in some laboratory animal studies (9). However, exposure is not specific to meat intake, as greater exposure may occur through consumption of other dietary sources such as vegetables or cereal products. Finally, some researchers have suggested that iron, particularly haem iron, may play a role in cancer development (4,10). Red meat is a primary source of haem iron, which is found naturally in meat as part of haemoglobin and myoglobin, although relatively few studies have evaluated the potential role that this factor may play in cancer risk (11).
In 2007, the World Cancer Research Fund (WCRF), in collaboration with the American Institute for Cancer Research (AICR), released a summary report entitled, ‘Food, Nutrition, Physical Activity, and the Prevention of Cancer: a Global Perspective’(12). This second report (the first was issued in 1997 (13)), evaluated the scientific evidence pertaining to numerous dietary factors and their relation with 17 different types of cancer. Twenty-two panellists formalized conclusions and recommendations based on the scientific literature that was assembled, synthesized and disseminated by independent international working groups. The WCRF/AICR panel judged that consumption of red meat is a ‘convincing’ cause of colorectal cancer (12), although there were numerous limitations to the available data. Specifically, the epidemiologic associations across the consortium of studies are relatively weak in magnitude (i.e. relative risk [RR] < 1.5), most individual studies have not observed statistically significant associations, there is no clear evidence of dose–response, and patterns of associations vary by study characteristics. Moreover, red meat is defined and analysed heterogeneously across studies. Despite their judgment, WCRF/AICR does not suggest that people exclude red meat from their diet; instead, they recommend that individuals who eat red meat should consume less than 500 g (18 oz) per week, and that the population average consumption of red meat should be no more than 300 g (11 oz) per week (12). This recommendation is generally consistent with the current red meat consumption levels based on national survey data (14,15).
While acknowledging that WCRF/AICR embarked on a comprehensive, ambitious and arduous foray into the epidemiology surrounding red meat and colorectal cancer (in addition to numerous other dietary factors and cancer endpoints), the judgments and conclusions from a public health perspective have not been met with scientific consensus. In an editorial by researchers at the International Agency for Research on Cancer, the scientific and methodological grounds for WCRF/AICR's ‘convincing’ classification for red meat and colorectal cancer were questioned due to strong previous conclusions for other dietary factors (e.g. fruits and vegetables) and cancer that were not supported by more recently published prospective studies (i.e. they did not substantiate prior associations) (16). Furthermore, International Agency for Research on Cancer raised questions about their evaluation process and classification system (16). Another commentary by Truswell suggested that the evidence supporting a change in conclusion from probable to convincing was incomplete and inaccurate because of some errors and omissions (17).
The purpose of this review is to synthesize and summarize the available epidemiologic studies of red meat intake and colorectal cancer, and to provide a scientific overview of the methodological and analytical complexity of evaluating this topic.