Association of Meat and Fat Intake With Liver Disease and Hepatocellular Carcinoma in the NIH-AARP Cohort

[Guest guest]

http://jnci.oxfordjournals.org/cgi/content/abstract/djq301

Journal of the National Cancer Institute Advance Access originally published

online on August 20, 2010

JNCI Journal of the National Cancer Institute 2010 102(17):1354-1365;

doi:10.1093/jnci/djq301

Published by Oxford University Press 2010.

--------------------------------------------------------------------------------

ARTICLES

Association of Meat and Fat Intake With Liver Disease and Hepatocellular

Carcinoma in the NIH-AARP Cohort

Neal D. Freedman, J. Cross, A. McGlynn, Christian C. Abnet,

Yikyung Park, Albert R. Hollenbeck, Arthur Schatzkin, E. Everhart, Rashmi

Sinha

Affiliations of authors: Division of Cancer Epidemiology and Genetics, National

Cancer Institute, National Institutes of Health, Department of Health and Human

Services, Rockville, MD (NDF, AJC, KAM, CCA, YP, AS, RS); AARP, Washington, DC

(ARH); Division of Digestive Diseases and Nutrition, National Institute of

Diabetes and Digestive and Kidney Diseases, National Institutes of Health,

Department of Health and Human Services, Bethesda, MD (JEE)

Correspondence to: Neal D. Freedman, PhD, MPH, Nutritional Epidemiology Branch,

Division of Cancer Epidemiology and Genetics, 6120 Executive Blvd, Rm 320, MSC

7361, Rockville, MD 20852 (e-mail: freedmanne@...).

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

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.

--------------------------------------------------------------------------------

CONTEXT AND CAVEATS

Prior knowledge

Few studies have examined whether meat and fat intake are associated with

chronic liver disease (CLD) and/or hepatocellular carcinoma.

Study design

Information concerning diet, CLD, and hepatocellular cancer incidence was

collected for 495 006 men and women, aged 50–71 years, from the National

Institutes of Health–AARP Diet and Health Study. All participants completed

food-frequency questionnaires in 1995–1996, and some completed an additional

food cooking questionnaire in 1996–1997. Incidence of hepatocellular carcinoma

was collected from state cancer registries until the end of 2003, and incidence

of CLD was determined from National Death Index records through the end of 2005.

Participants were divided into quintiles on the basis of meat, fat, or other

nutrient intakes, and hazard ratios for risk of CLD and hepatocellular carcinoma

were estimated using proportional hazards models.

Contribution

Red meat and saturated fat intakes were associated with increased risk of CLD

and hepatocellular carcinoma, whereas white meat intake was associated with less

than average risks of both diseases. Meat processing and its heme iron, nitrate,

and nitrite contents were associated with CLD but not with cancer.

Implication

Intake of red meat and saturated fats may increase hepatocellular cancer risk.

Limitations

The results are based on self-reported food intakes. They were stratified by

alcohol intake and other possible confounders; however, data concerning

hepatitis virus infections were unavailable.

From the Editors

Manuscript received July 28, 2009; revised June 22, 2010; accepted July 14,

2010.

[Guest guest]

http://jnci.oxfordjournals.org/cgi/content/abstract/djq301

Journal of the National Cancer Institute Advance Access originally published

online on August 20, 2010

JNCI Journal of the National Cancer Institute 2010 102(17):1354-1365;

doi:10.1093/jnci/djq301

Published by Oxford University Press 2010.

--------------------------------------------------------------------------------

ARTICLES

Association of Meat and Fat Intake With Liver Disease and Hepatocellular

Carcinoma in the NIH-AARP Cohort

Neal D. Freedman, J. Cross, A. McGlynn, Christian C. Abnet,

Yikyung Park, Albert R. Hollenbeck, Arthur Schatzkin, E. Everhart, Rashmi

Sinha

Affiliations of authors: Division of Cancer Epidemiology and Genetics, National

Cancer Institute, National Institutes of Health, Department of Health and Human

Services, Rockville, MD (NDF, AJC, KAM, CCA, YP, AS, RS); AARP, Washington, DC

(ARH); Division of Digestive Diseases and Nutrition, National Institute of

Diabetes and Digestive and Kidney Diseases, National Institutes of Health,

Department of Health and Human Services, Bethesda, MD (JEE)

Correspondence to: Neal D. Freedman, PhD, MPH, Nutritional Epidemiology Branch,

Division of Cancer Epidemiology and Genetics, 6120 Executive Blvd, Rm 320, MSC

7361, Rockville, MD 20852 (e-mail: freedmanne@...).

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

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.

--------------------------------------------------------------------------------

CONTEXT AND CAVEATS

Prior knowledge

Few studies have examined whether meat and fat intake are associated with

chronic liver disease (CLD) and/or hepatocellular carcinoma.

Study design

Information concerning diet, CLD, and hepatocellular cancer incidence was

collected for 495 006 men and women, aged 50–71 years, from the National

Institutes of Health–AARP Diet and Health Study. All participants completed

food-frequency questionnaires in 1995–1996, and some completed an additional

food cooking questionnaire in 1996–1997. Incidence of hepatocellular carcinoma

was collected from state cancer registries until the end of 2003, and incidence

of CLD was determined from National Death Index records through the end of 2005.

Participants were divided into quintiles on the basis of meat, fat, or other

nutrient intakes, and hazard ratios for risk of CLD and hepatocellular carcinoma

were estimated using proportional hazards models.

Contribution

Red meat and saturated fat intakes were associated with increased risk of CLD

and hepatocellular carcinoma, whereas white meat intake was associated with less

than average risks of both diseases. Meat processing and its heme iron, nitrate,

and nitrite contents were associated with CLD but not with cancer.

Implication

Intake of red meat and saturated fats may increase hepatocellular cancer risk.

Limitations

The results are based on self-reported food intakes. They were stratified by

alcohol intake and other possible confounders; however, data concerning

hepatitis virus infections were unavailable.

From the Editors

Manuscript received July 28, 2009; revised June 22, 2010; accepted July 14,

2010.