1 Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, MN, United States. Electronic address: Allen.firstname.lastname@example.org.
2 Department of Internal Medicine, Mayo Clinic, Rochester MN, United States.
3 Division of Biomedical Statistics and Informatics, Mayo Clinic, Rochester, MN, United States.
&Aims: Cancer is a major cause of death in nonalcoholic 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.
We identified all incident cases of NAFLD in a US population between 1997-2016. Subjects 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 tested by medical record review. The association between NAFLD versus obesity and cancer risk was examined using Poisson regression.
A total of 4,722 NAFLD subjects (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: 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 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).
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 obesity-cancer association.
We studied the incidence of malignancies in a community cohort of adults with nonalcoholic 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 nearly a 2-fold risk of developing cancers, predominantly of liver, gastrointestinal tract and uterus. The association with increased cancer risk was stronger in NAFLD than obesity.