What is driving higher rates of young-onset digestive tract cancers, including stomach, colorectal, liver, pancreatic, biliary tract, and gallbladder cancers? Possibly increased rates of nonalcoholic fatty liver disease, researchers suggest in a study published in the Journal of Clinical Oncology earlier this year (2023; doi: 10.1200/JCO.22.01740).
For the nationwide cohort study, the researchers analyzed data that included more than 5 million young adult Koreans. The data showed that regardless of age, sex, smoking status, alcohol consumption, and obesity status, nonalcoholic fatty liver disease was associated with a higher risk of digestive tract cancers. The cumulative incidence probability of each cancer type was consistently higher in individuals with nonalcoholic fatty liver disease than in those without it.
"Our findings suggest a crucial opportunity to reduce premature morbidity and mortality associated with young-onset digestive tract cancers in the next generation," the authors noted in the paper.
Study Details
More than 5 million individuals ages 20-39 participated in national health screening with the Korean National Health Insurance Service between 2009 and 2012. They were followed through December 2018 to track the incidence of young-onset digestive tract cancers, including esophageal, stomach, colorectal, liver, pancreatic, biliary tract, and gallbladder cancers.
The fatty liver index was used as a diagnostic biomarker for nonalcoholic fatty liver disease. During the follow-up period, 14,565 patients were newly diagnosed with young-onset digestive tract cancers. Those with nonalcoholic fatty liver disease were at increased risk of being diagnosed with one of these digestive tract cancers. The adjusted hazard ratios for increased risk of the following cancer types were the following: any type of digestive tract cancer: 1.16; stomach: 1.14; colorectal: 1.14; liver: 1.13; pancreatic: 1.23; biliary tract: 1.29; gallbladder: 1.53; and esophageal: 1.67.
A Look at the Findings
"While several prior studies evaluated the associations between nonalcoholic fatty liver disease and risk of gastrointestinal (GI) cancers, this nationwide analysis significantly extended the scope of the prior ones due to its large number of participants and outcomes," said Yin Cao, ScD, MPH, Associate Professor of Surgery in the Division of Public Health Sciences in the Department of Surgery at Washington University School of Medicine.
Cao was not involved in this recent research, but is a coauthor of a study published in 2022 that looked at the same question of whether nonalcoholic fatty liver disease was linked to digestive tract cancers in a UK Biobank cohort of patients (Hepatol Commun 2022; doi: 10.1002/hep4.2073). The research included older and young adults. The team prospectively examined the associations of nonalcoholic fatty liver disease risk as estimated by the Dallas Steatosis Index with risk of GI cancers overall and according to age of onset among 319,290 participants in the UK Biobank.
"We found that predicted nonalcoholic fatty liver disease risk was associated with an increased risk of liver and most GI cancers, and stronger associations were observed for cancers diagnosed at an earlier age (before age 60) compared to those diagnosed later (at age 60 or older)," Cao explained.
Bottom Line
While the new data align with Cao's earlier work, she said the generalizability of the findings should be limited to the Korean population. "Considering the variations in other risk factors, more studies are needed from other countries," she stated. However, these data do highlight this association between nonalcoholic fatty liver disease and digestive tract cancers as an important research question, as well as an issue for clinicians to be aware of.
"There is an emerging need to increase physicians' awareness of the higher risk of gastrointestinal cancers among individuals with nonalcoholic fatty liver disease," Cao said. "As we are seeing increasing incidence of multiple gastrointestinal cancers in younger adults globally, assessing nonalcoholic fatty liver disease risk in younger adults may emerge as an effective cancer prevention strategy."
Sarah DiGiulio is a contributing writer.