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September 04, 2019
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NAFLD regardless of obesity marks increased risk for liver, GI cancers

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Nonalcoholic fatty liver disease correlated with an approximately 90% higher risk for liver and gastrointestinal cancers compared with patients without fatty liver disease, while the association between obesity without fatty liver disease and cancer was small.

“The prevalence of obesity has more than doubled in the last four decades and as a result, the incidence of nonalcoholic fatty liver disease (NAFLD) has increased substantially,” Alina M. Allen, MD, from the Mayo Clinic in Rochester, Minnesota, and colleagues wrote. “These unique epidemiologic observations reframe our understanding of the association between obesity and cancer risk. There is a continued need for better characterization of excess adiposity, because current measures of obesity, such as BMI, are insufficient and may overlook other potential key contributors to outcomes, based on ectopic fat distribution.”

Allen and colleagues enrolled 4,722 patients with NAFLD and 14,441 age- and sex-matched control participants in the study. Patients with NAFLD had higher proportions of obesity (66% vs. 35%), diabetes (33% vs. 9%), hypertension (46% vs. 26%) and dyslipidemia (59% vs. 33%) compared with controls.

During a median follow-up of 8 years (range, 1-21), more patients with NAFLD developed liver or gastrointestinal cancer (27% vs. 18%) for a 90% higher overall risk for malignancy (incidence rate ratio [IRR] = 1.9; 95% CI, 1.3-2.7).

Specifically, patients with NAFLD had increased risks for liver (IRR = 2.8; 95% CI 1.6-5.1), uterine (IRR = 2.3; 95% CI, 1.4-4.1), stomach (IRR = 2.3; 95% CI, 1.3-4.1), pancreas (IRR = 2; 95% CI, 1.2-3.3) and colon cancer (IRR = 1.8; 95% CI, 1.1-2.8).

While the researchers found that obesity correlated with a trend toward increased malignancy risk compared with patients with a BMI less than 30 kg/m2, patients with NAFLD had a twofold higher risk for incident cancer compared with both controls without obesity (IRR = 2; 95% CI, 0.8-1.4) and those with obesity (IRR = 2; 95% CI, 1.5-2.7).

“NAFLD may be a more important intermediary biomarker of cancer risk,” Allen and colleagues wrote. “In this cohort, the obesity-related risk was largely driven by NAFLD, while obesity in the absence of NAFLD had minimal association with malignancy risk. These findings serve as hypothesis-generators for future studies of biological mechanisms underpinning this link, to examine NAFLD as potential predictor by association or as a mediator on the causal pathway to the development of cancer.” – by Talitha Bennett

Disclosures: The authors report no relevant financial disclosures.