Association of meat and fat intake with liver disease and hepatocellular carcinoma in the NIH-AARP cohort.
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.


CONCLUSIONS
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.
Freedman
Neal D
ND
Nutritional Epidemiology Branch, Division of Cancer Epidemiology and Genetics, 6120 Executive Blvd., Rockville, MD 20852, USA. freedmanne@mail.nih.gov
Cross
Amanda J
AJ
McGlynn
Katherine A
KA
Abnet
Christian C
CC
Park
Yikyung
Y
Hollenbeck
Albert R
AR
Schatzkin
Arthur
A
Everhart
James E
JE
Sinha
Rashmi
R
D000368:Aged; D006528:Carcinoma, Hepatocellular / Q000453:epidemiology* / Q000209:etiology*; D015331:Cohort Studies; D004041:Dietary Fats / Q000008:administration & dosage*; D005247:Feeding Behavior; D005260:Female; D005500:Follow-Up Studies; D006509:Hepatitis B; D006801:Humans; D015994:Incidence; D008107:Liver Diseases / Q000453:epidemiology* / Q000209:etiology* / Q000401:mortality; D008113:Liver Neoplasms / Q000453:epidemiology / Q000209:etiology; D008297:Male; D008460:Meat / Q000009:adverse effects*; D008875:Middle Aged; D015999:Multivariate Analysis; D009749:Nutrition Surveys; D016016:Proportional Hazards Models; D011446:Prospective Studies; D012107:Research Design; D018570:Risk Assessment; D012307:Risk Factors; D014481:United States / Q000453:epidemiology
D004041:Dietary Fats