Better to Binge Than Regularly Tipple, Suggests GI Cancer Study

The risk for gastrointestinal (GI) cancers is known increase with alcohol use. That risk appears to be increased further in association with an increase in the frequency of alcohol use ― even in smaller amounts ― compared with irregularly drinking higher amounts or binge drinking, given similar weekly levels, new research shows.

Dr Jung Eun Yook

“The novel finding of the current study is that frequent drinking may be more dangerous than binge drinking with regard to GI cancers,” report first author Jung Eun Yook, MD, of Seoul National University Hospital, Seoul, Republic of Korea, and colleagues in an article published this month in JAMA Network Open.

“This finding suggests that repeated alcohol consumption events even at lower amounts of alcohol may have a greater carcinogenic effect on GI organs than the consumption of larger amounts of alcohol at a lower frequency,” the investigators write.

A possible reason behind the difference in risk may be that the chronic “carcinogenic insult” from regular alcohol use may promote cancer development, whereas less frequent, episodic alcohol exposures may allow physiologic recovery, say the authors.

The results are from a population-based study that involved 11,737,467 participants in the Korean National Health System database who did not have cancer and who took part in a national screening program between January 2009 and December 2010.

They were followed from the year after their screening until either they had received a diagnosis of a GI cancer, death occurred, or the end of December 2017.

During a median follow-up of 6.4 years, 319,202 (2.7%) of those in the study developed a GI cancer.

The increase in the risk associated with alcohol consumption was dose dependent.

Compared with those who did not consume alcohol, the risk of developing GI cancer was higher for mild drinkers (adjusted hazard ratio [aHR], 1.04; 95% CI, 1.03 – 1.05), moderate drinkers (aHR, 1.14; 95% CI, 1.12 – 1.15), and heavy drinkers (aHR, 1.28; 95% CI, 1.26 – 1.29), after adjusting for age, sex, income, smoking status with intensity, regular exercise, body mass index, diabetes, hypertension, and dyslipidemia.

There was a linear association between the frequency of drinking and GI cancer risk, with an aHR of 1.39 for individuals who reported drinking every day (95% CI, 1.36 – 1.41). The risk for GI cancer increased with consumption of 5 to 7 units per occasion (aHR, 1.15). Notably, there were no similar increases with higher intake, including intake of 8 to 14 units per occasion (aHR, 1.11; 95% CI, 1.09 – 1.12), and even up to more than 14 units per occasion (aHR, 1.11; 95%CI, 1.08 – 1.14), in comparison with an intake of 5 to 7 units per occasion.

“Given similar weekly alcohol consumption levels, the risk of GI cancer increased with a higher frequency of drinking and decreased with a higher amount per occasion,” the authors write.

“Most previous studies just assess alcohol consumption as a total amount, [such as] drinks per occasion times occasion per week equals drinks per week [and] grams per week,” co-author Dong Wook Shin, MD, DrPH, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea, told Medscape Medical News.

“But it was not known whether frequent drinking with small amount is more harmful than binge drinking, given a similar level of total drinking,” Shin said.

The increased risk associated with frequent drinking was generally similar with respect to esophageal, gastric, colorectal, biliary, and pancreatic cancer.

An exception was liver cancer, which showed a slightly decreased risk among mild drinkers (aHR, 0.91; 95% CI, 0.89 – 0.93).

Of note, the association between alcohol intake and the incidence of GI cancer was lower among women than men in terms of weekly consumption, frequency, and amount of alcohol consumed per occasion.

The associations between drinking and cancer type in terms of esophageal and liver cancers were similar between men and women. However, the alcohol-related risk for colorectal, biliary, and pancreatic cancers was less prominent for women.

Possible Mechanisms Related to Regular Drinking

A factor that might account for the increase in GI cancer risk with frequent drinking is that regular alcohol consumption “promotes the accumulation of cell divisions in the stem cells that maintain tissues in homeostasis,” the authors explain.

Another possible explanation is that long-term alcohol exposure may promote carcinogenesis, whereas less frequent exposure might allow “physiological homeostasis,” the authors write. They note that in vivo experiments have shown that duration and dose of alcohol exposure have been linked to cancer development.

Importantly, the findings support the importance of reducing the frequency of alcohol use to prevent cancer, the authors note.

“Alcohol users who have a glass of wine or beer during dinner every day may develop more cancer than people who occasionally consume several drinks,” they caution.

Genetics, Self-Reporting Considerations

In a related commentary, John D. Potter, MBBS, PhD, of the Research Center for Hauora and Health, Massey University, Wellington, New Zealand, noted that in addition to supporting the known link between alcohol and cancers of the esophagus, colorectum, and liver, the study “strengthens evidence for a role of alcohol in stomach, biliary tract, and pancreas cancers.”

In comparison with nondrinkers, those who reported heavy drinking were much more likely to be smokers (51.6% vs 9.0%); however, the study adjusted for smoking.

“Because the researchers were able to control for tobacco, this last finding [regarding the association with cancers of the stomach, biliary tract, and pancreas] is particularly informative,” Potter notes.

An important caveat is that more than a quarter of the Korean population is known to have an inactive form of the aldehyde dehydrogenase gene (ALDH2), which could have effects on alcohol metabolism as well as the risk for cancer, Potter writes.

“This common polymorphism in ALDH2 (ALDH2 rs671 [c.1510G>A (Glu504Lys)]) has paradoxical effects,” he writes.

“[I]t increases the level of acetaldehyde in the blood of drinkers, which in turn increases the risk of cancer because acetaldehyde is a key player in the carcinogenicity of alcoholic beverages,” Potter explains.

“On the other hand, the accumulation of acetaldehyde and the resultant flushing response are sufficiently unpleasant that they tend to reduce alcohol consumption among those with the Lys allele.”

The study results may therefore not be generalizable to a population in which the distribution of the variation in the ALDH2 enzyme differs, Potter adds.

The lower prevalence of the inactive form (in North America, for instance) would mean that this lower prevalence was not a constraint on individuals’ drinking behavior as it is for some in Korea, Potter explains.

He notes another consideration: the underreporting of alcohol use is a well-known limitation of studies involving the assessment of alcohol consumption.

Shin agreed that underreporting is a limitation.

“People tend to underestimate their alcohol use,” Shin told Medscape Medical News.

However, he noted that “our study participants are health-screening participants aged 40 years and older, [and] people who participate in health screening tend to have higher awareness and better health behavior than nonparticipants.”

The authors and Potter have disclosed no relevant financial relationships.

JAMA Netw Open. Published online August 18, 2021. Full text, Commentary

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