TY - JOUR
T1 - The risk of incident extrahepatic cancers is higher in non-alcoholic fatty liver disease than obesity – A longitudinal cohort study
AU - Allen, Alina M.
AU - Hicks, Stephen B.
AU - Mara, Kristin C.
AU - Larson, Joseph J.
AU - Therneau, Terry M.
N1 - Funding Information:
Alina M. Allen: National Institute of Diabetes and Digestive and Kidney Diseases ( K23DK115594 ); American College of Gastroenterology Junior Faculty Development Grant . This study was made possible using the resources of the Rochester Epidemiology Project, which is supported by the National Institute on Aging of the National Institutes of Health under Award Number R01AG034676 . The funding sources did not have any role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, or approval of the manuscript; and decision to submit the manuscript for publication.
Funding Information:
Alina M. Allen: National Institute of Diabetes and Digestive and Kidney Diseases (K23DK115594); American College of Gastroenterology Junior Faculty Development Grant. This study was made possible using the resources of the Rochester Epidemiology Project, which is supported by the National Institute on Aging of the National Institutes of Health under Award Number R01AG034676. The funding sources did not have any role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, or approval of the manuscript; and decision to submit the manuscript for publication.
Publisher Copyright:
© 2019 European Association for the Study of the Liver
PY - 2019/12
Y1 - 2019/12
N2 - Background & Aims: Cancer is a major cause of death in patients with non-alcoholic fatty liver disease (NAFLD). Obesity is a risk factor for cancers; however, the role of NAFLD in this association is unknown. We investigated the effect of NAFLD versus obesity on incident cancers. Methods: We identified all incident cases of NAFLD in a US population between 1997-2016. Individuals with NAFLD were matched by age and sex to referent individuals from the same population (1:3) on the index diagnosis date. We ascertained the incidence of cancer after index date until death, loss to follow-up or study end. NAFLD and cancer were defined using a code-based algorithm with high validity and tested by medical record review. The association between NAFLD or obesity and cancer risk was examined using Poisson regression. Results: A total of 4,722 individuals with NAFLD (median age 54, 46% male) and 14,441 age- and sex-matched referent individuals were followed for a median of 8 (range 1–21) years, during which 2,224 incident cancers occurred. NAFLD was associated with 90% higher risk of malignancy: incidence rate ratio (IRR) = 1.9 (95% CI 1.3–2.7). The highest risk increase was noted in liver cancer, IRR = 2.8 (95% CI 1.6–5.1), followed by uterine IRR = 2.3 (95% CI 1.4–4.1), stomach IRR = 2.3 (95% CI 1.3–4.1), pancreas IRR = 2.0 (95% CI 1.2–3.3) and colon cancer IRR = 1.8 (95% CI 1.1–2.8). In reference to non-obese controls, NAFLD was associated with a higher risk of incident cancers (IRR = 2.0, 95% CI 1.5–2.9), while obesity alone was not (IRR = 1.0, 95% CI 0.8–1.4). Conclusions: NAFLD was associated with increased cancer risk, particularity of gastrointestinal types. In the absence of NAFLD, the association between obesity and cancer risk is small, suggesting that NAFLD may be a mediator of the obesity-cancer association. Lay summary: We studied the incidence of malignancies in a community cohort of adults with non-alcoholic fatty liver disease (NAFLD) in reference to age- and sex-matched adults without NAFLD. After 21 years of longitudinal follow-up, NAFLD was associated with a nearly 2-fold increase in the risk of developing cancers, predominantly of the liver, gastrointestinal tract and uterus. The association with increased cancer risk was stronger in NAFLD than obesity.
AB - Background & Aims: Cancer is a major cause of death in patients with non-alcoholic fatty liver disease (NAFLD). Obesity is a risk factor for cancers; however, the role of NAFLD in this association is unknown. We investigated the effect of NAFLD versus obesity on incident cancers. Methods: We identified all incident cases of NAFLD in a US population between 1997-2016. Individuals with NAFLD were matched by age and sex to referent individuals from the same population (1:3) on the index diagnosis date. We ascertained the incidence of cancer after index date until death, loss to follow-up or study end. NAFLD and cancer were defined using a code-based algorithm with high validity and tested by medical record review. The association between NAFLD or obesity and cancer risk was examined using Poisson regression. Results: A total of 4,722 individuals with NAFLD (median age 54, 46% male) and 14,441 age- and sex-matched referent individuals were followed for a median of 8 (range 1–21) years, during which 2,224 incident cancers occurred. NAFLD was associated with 90% higher risk of malignancy: incidence rate ratio (IRR) = 1.9 (95% CI 1.3–2.7). The highest risk increase was noted in liver cancer, IRR = 2.8 (95% CI 1.6–5.1), followed by uterine IRR = 2.3 (95% CI 1.4–4.1), stomach IRR = 2.3 (95% CI 1.3–4.1), pancreas IRR = 2.0 (95% CI 1.2–3.3) and colon cancer IRR = 1.8 (95% CI 1.1–2.8). In reference to non-obese controls, NAFLD was associated with a higher risk of incident cancers (IRR = 2.0, 95% CI 1.5–2.9), while obesity alone was not (IRR = 1.0, 95% CI 0.8–1.4). Conclusions: NAFLD was associated with increased cancer risk, particularity of gastrointestinal types. In the absence of NAFLD, the association between obesity and cancer risk is small, suggesting that NAFLD may be a mediator of the obesity-cancer association. Lay summary: We studied the incidence of malignancies in a community cohort of adults with non-alcoholic fatty liver disease (NAFLD) in reference to age- and sex-matched adults without NAFLD. After 21 years of longitudinal follow-up, NAFLD was associated with a nearly 2-fold increase in the risk of developing cancers, predominantly of the liver, gastrointestinal tract and uterus. The association with increased cancer risk was stronger in NAFLD than obesity.
KW - Epidemiology
KW - NAFLD
KW - NASH
KW - Natural history
KW - Outcomes
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U2 - 10.1016/j.jhep.2019.08.018
DO - 10.1016/j.jhep.2019.08.018
M3 - Article
C2 - 31470068
AN - SCOPUS:85073710856
VL - 71
SP - 1229
EP - 1236
JO - Journal of Hepatology
JF - Journal of Hepatology
SN - 0168-8278
IS - 6
ER -