NAFLD Tied To Risk Of Gastrointestinal, Lung, Breast, And Gynecological Cancers

People with non-alcoholic fatty liver disease (NAFLD) are at increased risk of developing several types of extrahepatic cancers, a meta-analysis of observational cohort studies suggests.

Researchers examined data from 10 studies with a total of 182,202 participants (mean age 51 years), including 45,218 (24.8%) who had NAFLD at baseline. Over a median follow-up period of 5.8 years, people with NAFLD had a 1.2-fold to 2-fold increased risk of developing several gastrointestinal cancers as well as lung, breast, and gynecological malignancies.

"It is currently uncertain whether NAFLD is associated with an increased risk of extrahepatic cancers simply as a consequence of the shared metabolic risk factors including obesity and diabetes, or whether NAFLD itself may contribute to the development of extrahepatic cancers, independent of these shared risk factors," said senior study author Dr. Giovanni Targher of the department of medicine at the University of Verona, in Italy.

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"However, these data may help to increase clinician awareness of the need for prevention and early diagnosis of certain types of extrahepatic cancers related to NAFLD," Dr. Targher said by email.

For the meta-analysis, researchers calculated pooled random effects hazard ratios for a wide range of extrahepatic cancers to determine the association with NAFLD.

They found a significantly higher risk of esophageal cancers (hazard ratio 1.93), stomach cancer (HR 1.81), pancreatic cancer (HR 1.84), colorectal adenomas and cancer (HR 1.40 and 1.64, respectively), thyroid cancer (HR 2.63), lung cancer (HR 1.30), urinary cancers (HR 1.33), breast cancer (HR 1.39), and female gynecological cancers (HR 1.62).

NAFLD was not significantly associated with prostate cancer or hematological cancers, the study also found.

One limitation of the analysis is the potential for selection bias, differential losses to follow-up, and residual confounding in the smaller studies included, the authors note in Gut.

However, previous research has linked NAFLD to a number of extrahepatic manifestations such as cardiovascular disease, sarcopenia, and gastrointestinal cancers, said Dr. Zobair Younossi, president of Inova Medicine Services and chairman of clinical research at Inova Health System in Falls Church, Virginia. The current study confirmed that NAFLD is associated with multiple gastrointestinal cancers as well as lung and breast cancer, Dr. Younossi, who wasn't involved in the study, said by email.

"This study emphasizes the importance of considering NAFLD as a systemic disease which is potentially associated with adverse liver outcomes as well as adverse outcomes related to other organs such as cardiac and cancers," Dr. Younossi said.

Results from the current study and previous research highlight the importance of clinicians encouraging weight loss in patients with NAFLD, said Dr. Dimitrios Koutoukidis of the University of Oxford in the UK.

"The current standard practice is that clinicians advise people with NAFLD to lose weight, however, going beyond that and offering them formal support to lose weight, such as referrals to weight management services, will lead to larger weight loss for more people," Dr. Koutoukidis, who wasn't involved in the study, said by email.

"This will improve NAFLD, reduce the risk for cardiovascular disease, and may reduce the risk of obesity-related cancers," Dr. Koutoukidis said.

—Lisa Rapaport

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