A study in the latest issue of the Alimentary Pharmacology & Therapeutics reviews the association between meat consumption and the risk of hepatocellular carcinoma.
Professor Zhu and colleagues conclude, "The present meta-analysis indicates that a high level of white meat or fish consumption can reduce the risk of HCC significantly, while intake of red meat, processed meat or total meat is not associated with HCC risk."
The association between meat consumption and the risk of hepatocellular carcinoma (HCC) is still inconclusive.
Professor Zhu and colleagues from China conducted a systematic review and meta-analysis to quantitatively assess the relationship between meat intake and the risk of HCC.
The team searched the PubMed, Web of Science and EMBASE databases for relevant studies published before 2013.
The summary relative risks were pooled using the fixed-effects model when no substantial heterogeneity was detected, otherwise, the random-effects model was used.
Heterogeneity and publication bias were also analyzed.
The team evaluated 7 cohort studies, and 10 case–control studies.
The researchers found that the pooled relative risks (RRs) of HCC for the highest vs. lowest consumption levels were 1.10 for red meat, 1.01 for processed meat, and 0.97 for total meat.
Moreover, white meat and fish consumption were found to be inversely associated with HCC risk, the summary relative risks were 0.69 and 0.78, respectively, and the results remained quite stable after stratification by the confounding factors.
Professor Zhu and colleagues conclude, "The present meta-analysis indicates that a high level of white meat or fish consumption can reduce the risk of HCC significantly, while intake of red meat, processed meat or total meat is not associated with HCC risk."
"Our findings suggest that dietary intervention may be a promising approach for prevention of HCC, which still need to be confirmed by further well-designed prospective studies and experimental research."
Full Text available @ Alimentary Pharmacology & TherapeuticsDiscussion Only
To the best of our knowledge, this is the first systematic review and meta-analysis to evaluate the association between meat intake and HCC risk. Our meta-analysis included a large sample size (4826 HCC cases and 1 670 093 participants), a wide variety of populations (Asians and non-Asians) and a long time span (from 1971 to 2010), and thus provided a most comprehensive quantitative evidence of the association between meat consumption and HCC risk by far. In this study, we failed to find a significant association between red meat or processed meat and HCC risk, which was different from other gastrointestinal cancers. However, our results firstly suggested that higher intake of fish and poultry were significantly associated with a lower risk of HCC, and similar results were obtained in subgroup analyses when stratified by study design, quality score, publication year and ethnicity.
Previous studies have suggested that high intake of red meat and processed meat were associated with an increased risk of several types of cancer, including colon cancer, gastric cancer, oesophagus cancer, pancreatic cancer and even lung cancer.[6-9] The link is biologically plausible, since red meat and processed meat contain high levels of cholesterol and saturated fat, and are associated with increased risk of obesity and diabetes, which are known as cancer risk factors.[37, 38] Also some known carcinogens including haeme iron, N-nitroso compounds (NOC) and heterocyclic amines are found in red meat and processed meat, and more of them may be produced in the process of cooking and digestion.[39-41] However, in the present meta-analysis, we found no significant association between HCC and red meat or processed meat consumption, our findings are consistent with the results from the recent EPIC study in Europe,[14] the JACC study in Japan,[30] and also some case–control studies.[15-18, 21] However, the pooled RRs for red meat in the meta-analysis was not very stable, publication year was found to mainly contribute to the heterogeneity. Especially, after removing the studies published before 2003, the combined RR was 1.44 (95% CI: 1.15–1.80), and a significant association (RR: 1.43; 95% CI: 1.08–1.90) was also yielded when analysed the only cohort studies. Since such phenomenon that the RRs changed over time was not observed in other studies of red meat and cancer,[8, 9, 18] there was still not enough evidence to rule out all the studies before 2003 in our meta-analysis. Nonetheless, this phenomenon might be partially explained by socioeconomic status (SES), which is closely related with meat consumption,[42] and also serves as an independent and synergistic predictor of HCC.[43] An obvious example is the case–control study published in 1991 from Thailand, which found meat consumption was inversely associated with HCC risk.[19] In addition, selection bias and random errors might also result in the heterogeneity. Collectively, no association was found between red meat and HCC risk based on the current meta-analysis, however, the possibility that red meat or processed meat might increase the risk of HCC significantly should be explored in the future studies.
It's surprising and interesting to find that both fish and white meat can reduce the risk of HCC in our meta-analysis, the results exhibited a high homogeneity, and remained robust after stratification by the confounding factors. Nutritionally, fish and white meat are a rich source of unsaturated fatty acids (PUFA) and have less cholesterol and saturated fat compared with red meat. Substantial evidence indicates that n-3 polyunsaturated fatty acids have some anti-inflammatory potential via inhibiting the synthesis of IL-1 and TNF,[44] which might help to prevent the occurrence of HCC considering that chronic inflammation plays an important role in the development of hepatocellular carcinoma. Of note, studies in vitro also showed that omega-3 polyunsaturated fatty acids inhibited the growth of hepatocellular carcinoma through blocking β-catenin and cyclooxygenase-2, providing molecular mechanism for utilisation of ω -3 PUFAs in HCC prevention.[45] Moreover, in the Japan Public Health Center-based Prospective Study, Sawada et al. reported that consumption of fish or n-3 PUFAs appeared to protect against the development of HCC even among subjects with HBV and/or HCV infection,[20] and Freedman et al. found an inverse association between white meat intake and risk of chronic liver disease (CLD) in the National Institutes of Health–AARP Diet and Health Study.[12] It is also found that n-3 PUFA supplementation can improve hepatic steatosis in patients with non-alcoholic fatty liver disease (NAFLD) in a pilot study, which is also a risk factor for hepatocellular carcinoma.[46] All of these evidences support a possible protective effect for fish and white meat on HCC development. Meta-analysis is one of most powerful to evaluate inconsistent results and provide a quantitative assessment, making our conclusion more convincing than any other previous study alone. Although it is still early to recommend fish or white meat for HCC prevention currently, future studies are urgently needed to confirm our findings.
We also have to admit several limitations in our study. Firstly, relatively small number of studies were included regarding a given meat type, which limited further stratified analysis by each confounder, and detailed data for further dose–response analysis was also unavailable. Secondly, methodological weaknesses in the original studies should also be taken into account, such as recall and selection bias, errors in diet assessment and insufficient adjustment for potential confounders including HBV/HCV status, diabetes mellitus, alcohol drinking and energy intake. All of these factors would influence our results. Thirdly, the meat consumption categories and exposure ranges were different across studies, and we adopted relative risks for the highest category of meat consumption vs. the lowest, this might contribute to the heterogeneity among the studies. Finally, since the publication selection was based on published articles in English, and the number of yielded studies was relatively small, possible publication bias was unavoidable, although no significant publication bias was found even when P < 0.1 was regarded to be statistically significant, except for the analysis of the fish group.
The incidence of HCC remains on an increasing trend worldwide in past decades,[4] which has been supposed to be partially contributed by the prevalence of obesity and diabetes, especially in some Western countries.[3, 4] Both obesity and diabetes are closely related with lifestyles and dietary habits, therefore, dietary intervention might be an effective approach to prevent the incidence of HCC.[47] In consideration of the limitations above in the study, it is still too early to conclude that fish or white meat intake indeed significantly decreases the risk of HCC, and also it is quite possible that white meat or fish intake is actually a surrogate marker for other risk factors associated with HCC, despite adjustment for potential confounders. More detailed information about carbohydrate intake may be helpful to use if available in future studies.
In summary, the results of our meta-analysis demonstrate that the consumption of fish or white meat is inversely related with the risk of HCC, while intake of red meat, processed meat or total meat has no significant association with HCC risk. Our findings have important public health implications for the prevention of HCC by changing diet patterns. Further well-designed prospective studies with large sample sizes and long term follow-up are warranted to support our conclusions, additional experimental and molecular research are also needed to explore the possible mechanism involved.
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