Sweetened beverage consumption and risk of liver cancer by diabetes status: A pooled analysis

1Introduction

Worldwide, liver cancer is the sixth most frequently occurring cancer and the third largest contributor to cancer mortality [1] . In the U.S., where 42,230 cases of liver cancer are predicted to occur in 2021 [2] , a number of factors are known to increase risk. These factors include excessive alcohol consumption, hepatitis C virus (HCV), hepatitis B virus (HBV), cigarette smoking, non-alcoholic fatty liver disease, obesity, and type 2 diabetes [34] . The combined population attributable fraction of these factors, however, is estimated at 59.5%, so 40.5% of risk remains poorly explained [5] . It is possible that dietary factors such as sweetened beverages are linked to liver cancer, as sweetened beverage consumption has been linked to non-alcoholic fatty liver disease, obesity, and type 2 diabetes 678910 .

Beverages can be sweetened by either sugar or by artificial sweeteners such as aspartame, sucralose, and saccharin. It is unclear, however, if either sugar sweetened beverages (SSB) or artificially sweetened beverages (ASB) contribute to liver cancer risk. A recent meta-analysis of one ASB, artificially sweetened (AS) soda, and gastrointestinal cancers reported that consumption associated with a 28% increase in liver cancer risk [11] . The literature on SSB consumption and liver cancer risk is also limited [1213] . In the U.S., where there is very high sweetened beverage consumption [1415] , only one prospective study of sweetened beverage consumption and liver cancer has been reported [16] .

Many persons with diabetes are advised to limit SSB consumption, therefore consumption can vary widely between persons with and without diabetes [17] . A U.S. national survey found that 34.7% of person without diabetes reported drinking sweetened beverages at least once per day, while only 22.0% of persons with diabetes reported drinking sweetened beverages at least once a day [17] . Based on the likelihood of different sweetened beverage consumption exposure, the current study examined the relationship between sweetened beverage consumption and liver cancer risk by diabetes status.