Alcohol-Attributable Cancer Mortality Trends in the US

"Alcohol remains a leading yet modifiable risk factor for cancer. This systematic analysis presents one of the first comprehensive assessments of alcohol-attributable cancer mortality trends in the USA, revealing a twofold increase in deaths from 1990 to 2023. These findings align with prior national data demonstrating rising alcohol-related mortality, including a similar estimate of 20,216 deaths reported for 2020–2021 from another database³⁰ and 21,860 deaths attributable to alcohol-attributable liver disease in a separate analysis of GBD 2021 data.³¹ On evaluating based on sex, while overall alcohol attributable ASMR increased among males, it declined among females in all ages, in contrast to previously published analyses of GBD 2021.³¹ However, the proportion of cancer deaths attributable to alcohol increased substantially for male and female sexes. Our post hoc analysis also showed that while overall cancer mortality declined across all groups, alcohol-attributable mortality increased in males and remained stable or declined modestly in females, indicating that alcohol-attributable mortality has rather shown discordant upward trends.

"Notably, males exhibited higher alcohol-attributable mortality across nearly all cancer types, with particularly stark differences in liver cancer. Males tend to initiate alcohol use earlier and are more likely to engage in hazardous drinking.³² However, evolving patterns and biological differences, such as lower alcohol dehydrogenase activity, also place females at an increased risk.^33,34 In addition, age-specific patterns also revealed a substantial burden among older adults. While the current GBD analysis does not permit direct assessment of cumulative lifetime alcohol exposure, prior epidemiologic studies suggest that alcohol-related carcinogenesis could reflect a cumulative effect over time for older populations.³⁵ Among 55 years and older, liver cancer was the leading alcohol-related cause of death in males and third in females. Alcohol has a well-established direct association with the development of hepatocellular carcinoma.^36,37 In addition to its independent carcinogenic potential, alcohol frequently acts synergistically with other major etiologies, including chronic viral hepatitis, obesity, and metabolic dysfunction-attributable steatotic liver disease (MASLD).³⁷ As a result, alcohol contributes meaningfully to the global burden of liver cancer even when it is not the primary underlying etiology, a consideration that is relevant both to clinical practice and to GBD attribution frameworks.^4,38,39 In the updated 2023 GBD analysis, pancreatic cancer showed the second greatest increase in alcohol-attributable ASMR (after liver cancer) in adults aged 55 years and older for male and female sexes, the second highest rise in females aged 20–54, and the third highest in males aged 20–54. A large transcontinental prospective study (1980–2013) reported an alcohol–pancreatic cancer association independent of sex and smoking with associations more particularly evident for baseline alcohol intake of at least 15 g/day in women and 30 g/day in men.⁴⁰ These findings highlight alcohol's significant contribution to pancreatic cancer burden, with each additional 10 g per day of intake driving a measurable 3 percent increase in overall risk–reinforcing the critical role of alcohol reduction in pancreatic cancer prevention.⁴⁰

"In females, breast cancer accounted for the highest alcohol-attributable mortality. Like our study, a study from New Zealand found that breast cancer accounted for 61% of all female alcohol-attributable cancer deaths.⁴¹ Alcohol can elevate serum estrogen concentrations and activate estrogen receptor-dependent pathways, contributing to the development and progression of breast cancers.^9,42 Notably, alcohol consumption has been repeatedly linked to elevated breast cancer risk, even at intake levels as low as 5–15 g/day with meta-analyses demonstrating a dose–response relationship.^9,43 GLOBOCAN had estimated that 9.8/100,000 breast cancer cases in females in North America were attributable to alcohol.⁹ Similar to breast cancer, alcohol may influence prostate cancer through increased estrogen levels and reduced androgens and sex hormone–binding globulin.^44,45 In our study, prostate cancer showed an upward trend in percentage of ASMR attributable to alcohol (11% for 20–54; 29.5% for 55 years and older). Prior studies report a modest association between heavy alcohol intake and high-grade prostate cancer, likely mediated by oxidative stress–induced DNA damage and altered testosterone metabolism due to low sex hormone–binding globulin.⁴⁶ Study by GLOBOCAN also found similar findings with a direct association of alcohol with prostate cancer incidence (r 0.61) and prostate cancer mortality (r 0.30).⁴⁴"