Heavy alcohol consumption is associated with an increased risk for young-onset pancreatic cancer, according to a large nationwide cohort study conducted in South Korea.

These findings highlight the need to raise public awareness of heavy drinking as a modifiable risk factor for young-onset pancreatic cancer, reported lead author Joo-Hyun Park, MD, PhD, of Korea University College of Medicine, Ansan, Republic of Korea, and colleagues.

“Given the rapidly increasing incidence of young-onset pancreatic cancer worldwide, we aimed to evaluate the dose-response association between alcohol consumption and the risk of this disease,” the investigators wrote in the Journal of Clinical Oncology.

Alcohol and Pancreatic Cancer Link Seen in Older Patients

Previous research has suggested a link between alcohol consumption and pancreatic cancer, Park and colleagues wrote.

For example, Medscape Medical News recently covered a global pooled analysis of more than 2 million individuals. The study reported an association between daily alcohol consumption and a modest increase in the risk for pancreatic cancer, including a threshold effect: risk became statistically significant at approximately 2-3 standard drinks per day for men and 1-2 drinks per day for women.

That study population, however, had a median age of 57, reflecting the focus on older adults seen in prior research on this topic. In their new publication, Park and colleagues noted that the majority of cases in prior studies were diagnosed after 70 years.

“Consequently, evidence on the dose-response relationship between alcohol consumption and young-onset pancreatic cancer is sparse, leaving a critical gap in understanding alcohol’s role in the disease at younger ages,” they wrote.

Heavy Drinking Tied to Elevated Risk

To address this knowledge gap, Park and colleagues analyzed data from 6,263,770 individuals aged 20-39 years who underwent a health screening between 2009 and 2012 through the Korean National Health Insurance Service, which includes about 97% of the South Korean population.

Participants were followed through 2020 using linked claims and registry data, with alcohol intake assessed at baseline using self-reported questionnaires, then converted to grams of ethanol per day. Participants were categorized as nondrinkers, light-to-moderate drinkers (less than 30 g/d for men and less than 16 g/d for women), or heavy drinkers (at least 30 g/d for men and at least 16 g/d for women).

(In Korea, one standard alcohol drink has 8 g of ethanol, meaning heavy male drinkers were consuming 3.75 drinks per day, while heavy female drinkers were consuming two drinks per day. In contrast, one standard alcoholic drink in the US contains 14 g of ethanol.)

Participants were also characterized by drinking frequency as follows: 0 days per week, 1-2 days per week, 3-4 days per week, and at least 5 days per week.

During follow-up (median, 9.6 years among those without cancer), 1515 cases of young-onset pancreatic cancer were diagnosed, defined as diagnosis before age 50.

After multivariable adjustment for potential confounders (smoking status, BMI, physical activity, income level, diabetes, hypertension, dyslipidemia, chronic kidney disease, and pancreatitis), heavy alcohol consumption was associated with a 19% increased risk for young-onset pancreatic cancer compared with being a nondrinker (adjusted hazard ratio [aHR], 1.19; 95% CI, 1.004-1.42).

Light-to-moderate alcohol consumption was not significantly associated with increased risk (aHR, 1.04; 95% CI, 0.92-1.17). However, alcohol consumption at least three times per week was associated with a 23% increased risk (aHR, 1.23; 95% CI, 1.01-1.51), whereas less frequent drinking was not.

Findings Support Appropriate Public Health Education

Leah Biller, MD, an assistant professor of medicine at Harvard Medical School and medical oncologist at the Dana-Farber Cancer Institute, Boston, agreed that the data support appropriate public health education.

“These findings reinforce the importance of counseling young adults to avoid or, at a minimum, significantly limit alcohol consumption given its association with cancer risk,” Biller told Medscape Medical News.

For individuals who choose to drink, Biller advised that intake should remain below 30 g/d for men (about two drinks) and below 16 g/d for women (about one drink).

Li Jiao, MD, MS, PhD, associate professor of gastroenterology and member of the Dan L. Duncan Comprehensive Cancer Center at Baylor College of Medicine, Houston, noted that the present findings are consistent with previous US data.

Specifically, she cited a smaller pooled case-control study from 2016, published in Pancreas, that evaluated a variety of risk factors for young-onset pancreatic cancer. It reported increased risk for young-onset pancreatic cancer once daily consumption reached 52 g of alcohol (approximately four drinks), while no increased risk was detected in those who drank less.

“In addition to young-onset pancreatic cancer, heavy alcohol consumption has also previously been associated with a higher risk of early-onset colorectal cancer,” Jiao told Medscape Medical News. “Limiting alcohol consumption may therefore help reduce not only cancer risk later in life but also the risk of cancers occurring earlier in adulthood.”

Jiao also pointed out that these new data fill a demographic gap beyond age.

“Asian populations have been underrepresented in prior research examining the association between alcohol consumption and pancreatic cancer risk, let alone young-onset pancreatic cancer,” Jiao said. “This nationwide cohort study conducted in Korea is characterized by the largest sample size of young-onset pancreatic cancer reported to date in the world, to my knowledge.”

Generalizing Findings and Other Limitations

Although the demographic composition addresses one data gap, it could also constrain generalizability, according to an accompanying editorial by Rachael Stolzenberg-Solomon, PhD, MPH, RD, of the National Cancer Institute.

Stolzenberg-Solomon noted that approximately 40% of the Korean population possesses an ALDH2 gene polymorphism that can cause alcohol flushing. The study lacked data to control for this genetic modifier, which could influence both alcohol intake and the accumulation of acetaldehyde, a known carcinogen.

Biller also acknowledged this limitation, noting that the specific thresholds seen in Korean alcohol drinkers might not translate directly to the US, where a higher proportion of individuals can more effectively clear acetaldehyde.

Even so, Biller argued that “the biologic mechanisms thought to link alcohol to carcinogenesis…as well as pancreatic injury…are likely conserved across populations,” meaning the findings are “still likely broadly generalizable” and support “ongoing discussion with young patients about alcohol consumption and cancer risk.”

Jiao expressed slightly more caution.

“Genetic composition, drinking patterns, obesity prevalence, dietary habits, and other factors can differ between the two populations and may influence the magnitude of the underlying association,” Jiao said. “Prospective cohorts of younger individuals in the US are needed to better understand the associations between lifestyle factors and the risk of various young-onset cancers in general Americans.”

Describing another potential limitation, Stolzenberg-Solomon noted that the study evaluated total pancreatic cancer without distinguishing pancreatic ductal adenocarcinoma from neuroendocrine tumors. Because neuroendocrine tumors occur more frequently in younger populations, it is unclear how tumor heterogeneity may have influenced the findings.

Furthermore, she pointed out that residual confounding from smoking cannot be fully excluded, because studies often find correlations between smoking and pancreatic cancer. In the new research, significant risk associations were observed only among current smokers, although the magnitude of the association was similar among never-smokers, Stolzenberg-Solomon wrote. Additionally, the Pancreas study referred to smoking as an “established risk factor” for pancreatic cancer.

Despite these caveats, Stolzenberg-Solomon concluded: “This research adds to the evidence that alcohol is associated with pancreatic cancer risk and supports implementation of public health recommendations that limit alcohol consumption for cancer prevention.”

The study was supported by Korea University and the national research funding agencies in Korea. The investigators disclosed having relationships with AstraZeneca, Bristol Myers Squibb, Roche, and others. Stolzenberg-Solomon, Biller, and Jiao reported having no conflicts of interest.