Higher consumption of sugar-sweetened beverages could be associated with an increased risk of hepatocellular carcinoma and intrahepatic cholangiocarcinoma, according to the results of a pooled analysis, whereas artificially-sweetened beverages may not be associated with hepatic cancer risk following adjustment for demographic, lifestyle, and metabolic factors.
Using pooled individual-level data from 11 prospective cohort studies conducted in the United States and Europe, investigators analyzed more than 1.5 million patients without a history of cancer at baseline. The participants were enrolled between 1980 and 2009 and followed through end-of-study dates ranging from 2000 to 2019. Beverage intake was assessed using validated food frequency questionnaires, and incident hepatic cancers were identified through cancer registries or medical record review. During follow-up, the investigators documented 2,811 hepatic cancer cases, including 1,699 hepatocellular carcinoma (HCC) cases and 444 intrahepatic cholangiocarcinoma (ICC) cases.
The study outcomes included incident hepatic cancer overall and HCC and ICC analyzed separately. The investigators evaluated artificially-sweetened beverage and sugar-sweetened beverage consumption per additional beverage consumed daily and adjusted for age, sex, race and ethnicity, established hepatic cancer risk factors, including body mass index, diabetes status, smoking status, alcohol intake, physical activity, coffee consumption, and total energy intake.
The investigators reported that each additional daily sugar-sweetened beverage was associated with a 10% higher likelihood of HCC and a 15% higher likelihood of ICC. Sugar-sweetened beverage intake was not associated with overall hepatic cancer risk in the primary multivariable analysis, although the investigators observed heterogeneity across the cohorts.
By contrast, artificially-sweetened beverage intake was not associated with hepatic cancer overall, HCC, or ICC following adjustment for confounding factors. Positive associations observed in minimally adjusted analyses were attenuated and no longer present following multivariable adjustment.
Subgroup analyses yielded similar findings among the participants with and without diabetes. The investigators found no evidence that diabetes status modified the associations between beverage intake and hepatic cancer risk. They also reported that subtype-specific findings for HCC and ICC were more consistent than findings for hepatic cancer overall and showed less heterogeneity across the studies.
Several limitations may warrant consideration. Beverage consumption was self-reported and measured at a single time point in most cohorts, limiting assessment of changes in intake over time. The investigators were unable to adjust for underlying liver disease, including metabolic dysfunction–associated steatotic liver disease and cirrhosis, across all cohorts. Information on hepatitis B and C virus infection status was incomplete, and most of the participants were from predominantly White populations in the United States and Europe, potentially limiting generalizability to regions where viral hepatitis is a major driver of hepatic cancer.
"Based on this study and prior research associating SSB with adverse outcomes, individuals may benefit from reducing their intake of SSB," wrote lead study author Cody Z. Watling, DPhil, of the Division of Cancer Epidemiology and Genetics at the National Cancer Institute, and colleagues.
Co–study author Staci L. Sudenga, PhD, MPH, reported personal fees from Merck outside the submitted work and co–study author Lorelei A. Mucci, ScD, MPH, reported equity options from Convergent Therapeutics outside the submitted work. The study authors reported no other conflicts of interest.
Source: JAMA Network Open
