Association of Meat and Fat Intake With Liver Disease and HCC
Association of Meat and Fat Intake With Liver Disease and HCC
Background Several plausible mechanisms, including fat, iron, heterocyclic amines, and N-nitroso compounds, link meat intake with chronic liver disease (CLD) and hepatocellular carcinoma (HCC). Few studies have investigated these associations.
Methods We prospectively examined the relationship between meat and associated exposures with CLD mortality (n = 551; not including HCC) and HCC incidence (n = 338) in 495 006 men and women of the National Institutes of Health–AARP Diet and Health Study. Hazard ratios (HRs) and 95% confidence intervals (CIs) for the fifth (Q5) vs the first (Q1) quintile were estimated from multivariable adjusted Cox proportional hazards regression models. All tests of statistical significance were two-sided.
Results We found inverse associations between white meat and risk of CLD (HR = 0.52, 95% CI = 0.39 to 0.70, 7.5 vs 18.2 cases per 100 000 person-years) and HCC (HR = 0.52, 95% CI = 0.36 to 0.77, 5.8 vs 14.3 cases per 100 000 person-years). Red meat was associated with higher risk of CLD (HR = 2.59, 95% CI = 1.86 to 3.61, 22.3 vs 6.2 cases per 100 000 person-years) and HCC (HR = 1.74, 95% CI = 1.16 to 2.61, 14.9 vs 5.7 cases per 100 000 person-years). Among fat types, results were strongest for saturated fat (for CLD, HR = 3.50, 95% CI = 2.48 to 4.96, 23.0 vs 6.5 cases per 100 000 person-years; for HCC, HR = 1.87, 95% CI = 1.23 to 2.85, 14.5 vs 6.3 cases per 100 000 person-years). After mutual adjustment, risk estimates persisted for saturated fat, red meat, and white meat. Heme iron, processed meat, nitrate, and nitrite were positively associated with CLD but not with HCC. Individual heterocyclic amines, 2-amino-3,4,8-trimethylimidazo[4,5,-f]quinoxaline (DiMeIQx), 2-amino-3,8-dimethylimidazo[4,5-f] quinoxaline (MeIQx), and 2-amino-1-methyl-6-phenyl-imidazo[4,5-b]pyridine (PhIP), were not associated with either outcome.
Conclusion Our results suggest that red meat and saturated fat may be associated with increased CLD and HCC risk, whereas white meat may be associated with reduced risk.
Hepatocellular carcinoma (HCC) is the sixth most common incident cancer and third most common cause of cancer-related mortality worldwide. Strong risk factors for HCC have been identified, including exposure to aflatoxins, excess alcohol consumption, and chronic infection with hepatitis B virus (HBV) or hepatitis C virus (HCV). Exposure to these risk factors can injure the liver and lead to chronic liver disease (CLD). Individuals with CLD are at substantial risk of dying from its complications and also are at high risk of developing HCC. A substantial proportion of HCC occurs in patients without exposure to aflatoxins, alcohol, HBV, or HCV, particularly in the United States and other Western countries, suggesting the importance of additional risk factors.
In contrast with many other cancers, relatively few studies have investigated the association of diet and HCC risk. Most existing studies have had a case–control design that assessed diet after HCC diagnosis, at which stage the health of individuals can be compromised, perhaps affecting the accuracy of dietary recall. Few studies have investigated the association of white meat intake with HCC risk and little or no information is available regarding the role of either red or white meat in CLD.
Recently, a positive association between red meat intake and liver cancer was found in the prospective National Institutes of Health (NIH)–AARP (formerly known as the American Association of Retired Persons) Diet and Health Study, as part of an analysis of all cancers. In this report, we investigate several mechanisms that may underlie this association, along with the possible role of white meat. Red meat is an important dietary source of saturated and monounsaturated fatty acids. Fatty acid deposition in the liver can lead to nonalcoholic fatty liver disease that may increase the risk of CLD and HCC. Alternatively, red meat contains high amounts of bioavailable heme iron. Individuals with hemochromatosis, an iron overload disease, have substantially increased liver cancer risk, excess dietary iron contributes to risk of CLD and HCC in several parts of Africa, and phlebotomy and low iron diets are a treatment for chronic HCV and thus might lower liver cancer risk. Whether moderate dietary iron intake plays a role in the development of CLD and HCC is unclear. Heterocyclic amines (HCA) and polycyclic aromatic hydrocarbons, carcinogens produced during high-temperature cooking, and N-nitroso compounds formed from nitrate and nitrate in processed meats could also play a role. In primates and in other animals, high doses of HCAs or N-nitroso compounds cause liver tumors. We examined associations of meat and meat-related exposures with both CLD mortality and HCC incidence because consistent associations for both endpoints would suggest that these exposures affect liver disease progression.
Abstract and Introduction
Abstract
Background Several plausible mechanisms, including fat, iron, heterocyclic amines, and N-nitroso compounds, link meat intake with chronic liver disease (CLD) and hepatocellular carcinoma (HCC). Few studies have investigated these associations.
Methods We prospectively examined the relationship between meat and associated exposures with CLD mortality (n = 551; not including HCC) and HCC incidence (n = 338) in 495 006 men and women of the National Institutes of Health–AARP Diet and Health Study. Hazard ratios (HRs) and 95% confidence intervals (CIs) for the fifth (Q5) vs the first (Q1) quintile were estimated from multivariable adjusted Cox proportional hazards regression models. All tests of statistical significance were two-sided.
Results We found inverse associations between white meat and risk of CLD (HR = 0.52, 95% CI = 0.39 to 0.70, 7.5 vs 18.2 cases per 100 000 person-years) and HCC (HR = 0.52, 95% CI = 0.36 to 0.77, 5.8 vs 14.3 cases per 100 000 person-years). Red meat was associated with higher risk of CLD (HR = 2.59, 95% CI = 1.86 to 3.61, 22.3 vs 6.2 cases per 100 000 person-years) and HCC (HR = 1.74, 95% CI = 1.16 to 2.61, 14.9 vs 5.7 cases per 100 000 person-years). Among fat types, results were strongest for saturated fat (for CLD, HR = 3.50, 95% CI = 2.48 to 4.96, 23.0 vs 6.5 cases per 100 000 person-years; for HCC, HR = 1.87, 95% CI = 1.23 to 2.85, 14.5 vs 6.3 cases per 100 000 person-years). After mutual adjustment, risk estimates persisted for saturated fat, red meat, and white meat. Heme iron, processed meat, nitrate, and nitrite were positively associated with CLD but not with HCC. Individual heterocyclic amines, 2-amino-3,4,8-trimethylimidazo[4,5,-f]quinoxaline (DiMeIQx), 2-amino-3,8-dimethylimidazo[4,5-f] quinoxaline (MeIQx), and 2-amino-1-methyl-6-phenyl-imidazo[4,5-b]pyridine (PhIP), were not associated with either outcome.
Conclusion Our results suggest that red meat and saturated fat may be associated with increased CLD and HCC risk, whereas white meat may be associated with reduced risk.
Introduction
Hepatocellular carcinoma (HCC) is the sixth most common incident cancer and third most common cause of cancer-related mortality worldwide. Strong risk factors for HCC have been identified, including exposure to aflatoxins, excess alcohol consumption, and chronic infection with hepatitis B virus (HBV) or hepatitis C virus (HCV). Exposure to these risk factors can injure the liver and lead to chronic liver disease (CLD). Individuals with CLD are at substantial risk of dying from its complications and also are at high risk of developing HCC. A substantial proportion of HCC occurs in patients without exposure to aflatoxins, alcohol, HBV, or HCV, particularly in the United States and other Western countries, suggesting the importance of additional risk factors.
In contrast with many other cancers, relatively few studies have investigated the association of diet and HCC risk. Most existing studies have had a case–control design that assessed diet after HCC diagnosis, at which stage the health of individuals can be compromised, perhaps affecting the accuracy of dietary recall. Few studies have investigated the association of white meat intake with HCC risk and little or no information is available regarding the role of either red or white meat in CLD.
Recently, a positive association between red meat intake and liver cancer was found in the prospective National Institutes of Health (NIH)–AARP (formerly known as the American Association of Retired Persons) Diet and Health Study, as part of an analysis of all cancers. In this report, we investigate several mechanisms that may underlie this association, along with the possible role of white meat. Red meat is an important dietary source of saturated and monounsaturated fatty acids. Fatty acid deposition in the liver can lead to nonalcoholic fatty liver disease that may increase the risk of CLD and HCC. Alternatively, red meat contains high amounts of bioavailable heme iron. Individuals with hemochromatosis, an iron overload disease, have substantially increased liver cancer risk, excess dietary iron contributes to risk of CLD and HCC in several parts of Africa, and phlebotomy and low iron diets are a treatment for chronic HCV and thus might lower liver cancer risk. Whether moderate dietary iron intake plays a role in the development of CLD and HCC is unclear. Heterocyclic amines (HCA) and polycyclic aromatic hydrocarbons, carcinogens produced during high-temperature cooking, and N-nitroso compounds formed from nitrate and nitrate in processed meats could also play a role. In primates and in other animals, high doses of HCAs or N-nitroso compounds cause liver tumors. We examined associations of meat and meat-related exposures with both CLD mortality and HCC incidence because consistent associations for both endpoints would suggest that these exposures affect liver disease progression.
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