This systematic literature review and meta-analysis, including 22 manuscripts from three cohort studies and 16 case-control studies evaluating several animal foods, suggested an increased endometrial cancer risk with meat consumption, particularly with red meat. Women in the highest category of meat or red meat consumption had a 39% and 48%, respectively, higher endometrial cancer risk, compared to the lowest category of consumption. Dose-response analyses indicated a 26% increase in risk per 100g/day of meat intake (95 % CI: 1.03–1.54), based on eight case-control studies and a 51% increase in risk per 100 g/day of red meat intake (95% CI: 1.19–1.93), based on seven case-control studies. These findings should be viewed with caution, given the high and significant heterogeneity among studies and because the only cohort study, the Iowa Women’s Health Study, [29
] evaluating the association with meat and red meat intake found no association. However, it should be pointed out that analyses from this cohort also failed to find an association between red meat and colorectal cancer, which has generally been supported by other cohort studies [5
]. The current epidemiologic literature does not support an association between dairy products and endometrial cancer. The evidence for poultry, fish, and eggs is limited and inconsistent. As for red meat, more studies, particularly cohort studies, are needed.
To our knowledge, this is the first comprehensive systematic literature review and meta-analysis evaluating the evidence for animal products and endometrial cancer risk. A narrative review of the literature of diet and endometrial cancer was included in the 1997 WCRF/AICR Report [4
]. Meat consumption was not mentioned in this report. The evidence for fish consumption was found to be inconsistent and insufficient, based on three studies [7
]. We excluded one of these studies [8
] because it did not show risk estimates, only a comparison of mean fish intake in cases and controls. We identified one cohort [29
] and nine case-control studies [7
] reporting on fish and found little evidence of an association. However, when we excluded the studies that did not adjust for total energy intake, there was an indication of an increased risk associated with fish consumption. Three case-control studies [7
] reporting on eggs were mentioned in the 1997 WCRF/AICR report, but again, the evidence was deemed insufficient. We identified one cohort [29
] and five case-control studies [7
] reporting on eggs, which, overall, provided inconsistent results. More studies are needed to make any conclusions regarding egg consumption and risk. Dairy products were not mentioned in the 1997 WCRF/AICR report. We found one cohort study [29
] and eight case-control studies [20
], and little support for a role of dairy food consumption on endometrial cancer risk.
There is a growing body of evidence linking red meat with certain cancers, particularly colorectal cancer [44
]. Several mechanisms have been proposed for a carcinogenic effect of red meat. It is known that the processing and preparation of meat may result in the generation of carcinogenic n-nitroso compounds and heterocylic amines [45
]. High red meat intake may result in higher pro-oxidant load from consumption of readily-absorbed heme iron, resulting in greater oxidative stress and potential for DNA damage [46
It has been postulated that higher meat consumption may also increase cancer risk because it may be associated with generally unhealthier dietary patterns, for example, lower fruit and vegetable and higher fat intakes. Its relatively high concentration of food energy may also be associated with higher total energy intake and higher body mass. Most of the studies took body mass index and total energy intake, but not all of them did. This should be kept in mind in both the interpretation of the current evidence and in the planning of future studies evaluating the role of meat intake on endometrial cancer risk.
Animal foods are also known to contain estradiol and its metabolites in various concentrations depending on several factors, including type of food, species, gender, physiological stage, and age [6
]. In addition, the administration of exogenous sex steroids for growth promotion in meat-producing animals has been a common agricultural practice in the United States for decades [48
]. However, the use of hormonal drugs in animal meat production is highly controversial, scientifically and politically. While most beef cattle in the US receive exogenous sex steroids, their use and import of meat from such animals is banned by the European Union [49
]. The European Commission’s Scientific Committee on Veterinary Measures relating to Public Health stated that estradiol 17β is a likely complete carcinogen, both initiating and promoting carcinogenesis, as partial justification of this ban [50
]. Unfortunately, the literature on red meat intake and endometrial cancer does not provide much insight into whether this is an important reason for the observed association, as we identified only one study conducted in Europe [23
] that examined this association.
Concerns have also been raised regarding cow’s milk as an important source of food estrogens [13
]; although sex hormone treatments are not used in dairy animals in the United States [48
], milk today is produced from pregnant cows [13
]. Interestingly, we did not find much evidence for a relationship between dairy product consumption and endometrial cancer. Fish may also contain environmental pollutants including endocrine disrupting chemicals with estrogenic activity, such as organochlorines residues or polychlorinated biphenyls (PCBs) [37
A limitation of the current body of literature is the lack of a clear definition of what foods should be included in the meat group. As shown in the , some studies have included composite meals, such as stews, which may contain vegetables and counteract the potential detrimental effect of meat. Fish was included in the meat group in some studies but not in others. In many studies what was included in the meat group was not specified. Clearly, future studies should aim towards more standardized definitions of meat, red meat, and other food groups.
Our meta-analyses were limited by the relatively small number of studies examining a given exposure, which precluded the evaluation of publication bias, or the conduct of more sophisticated sensitivity analyses and metaregression to ascertain possible causes of heterogeneity among studies. However, our systematic review and meta-analyses point to general trends in the data and underscore the need for additional population-based studies, and particularly prospective cohort studies, evaluating the relationship between animal product consumption and endometrial cancer risk.
In summary, the current epidemiologic literature, although limited, points to an increased endometrial cancer risk associated with meat and red meat intake. Because the current evidence is based mostly on case-control data, which may be more prone to selection and recall bias, no firm conclusions can be drawn at the present time. We encourage the evaluation of the role of red meat and other animal foods such as fish or eggs on endometrial cancer risk in cohort studies. Such analyses should control for the effects of body mass index and total energy intake, as well as other well-known risk factors for the disease. Although the most definitive nutrition-related factor to target to reduce endometrial cancer risk is obesity prevention, understanding the role of individual dietary factors may provide etiologic clues and additional strategies to prevent this disease.