In GI Cancer Risk, Does Alcohol Frequency or Quantity Matter More?

— Gastrointestinal cancer risk increased linearly with frequency of consumption, Korean study found

 Three mature South Korean men drink beer in a home.

Frequent drinking, rather than the amount of alcohol consumed per occasion, is a more important risk factor for incident gastrointestinal (GI) cancers, according to a large South Korean population-based study.

The risk of GI cancers -- including esophageal, stomach, colorectal, liver, biliary, and pancreatic cancers -- increased linearly with the frequency of alcohol consumption in a dose-dependent manner, with an adjusted HR (aHR) of 1.39 for daily drinking (95% CI 1.36-1.41), reported Dong Wook Shin, MD, MBA, DrPH, of Samsung Medical Center in Seoul, and colleagues.

And while there was an increased risk with consumption of up to 5 to 7 units per occasion (aHR 1.15, 95% CI 1.14-1.16), the risk did not increase further with higher consumption:

  • 8-14 units per occasion: aHR 1.11 (95% CI 1.09-1.12)
  • >14 units per occasion: aHR 1.11 (95% CI 1.08-1.14)

"These findings suggest that individuals should be counseled about regular low-dose alcohol use in addition to total amount of alcohol consumption or amount per occasion," the authors noted in JAMA Network Open.

In an accompanying commentary, John Potter, MBBS, PhD, of Massey University in Wellington, New Zealand, said that these findings not only strengthen the evidence of an association between alcohol consumption and esophageal, colorectal, and liver cancer, but also add evidence of its association with stomach, biliary, and pancreatic cancer -- a causal link that has not been well established in previous studies.

Shin and colleagues used the National Insurance System database to access data on 11,737,467 individuals (mean age 54.6 years, 52.2% women) without cancer who participated in a national health screening program from Jan. 1, 2009 to Dec. 31, 2010. They were categorized as non-drinkers, mild drinkers (0-104 g/week), moderate drinkers (105-209 g/week), and heavy drinkers (≥210 g/week), and evaluated according to drinking frequency and amount per occasion.

Drinkers made up 40.3% of the study population, comprised of mild drinkers (23.7%), moderate drinkers (9.5%), and heavy drinkers (7.1%).

Heavy drinkers were younger than non-drinkers (mean age 52.3 vs 56.4), much more likely to be smokers (51.6% vs 9.0%) and men (94.5% vs 28.9%), and engaged in more regular exercise (22.4% vs 18.2%) and had a slightly higher mean body mass index (24.4 vs 23.9). Heavy drinkers also had a higher prevalence of comorbidities compared with non-drinkers.

Participants were followed from the year after their health screening date until they received a diagnosis of GI cancer, died, or up to Dec. 31, 2017. Over a median of 6.4 years, 319,202 (2.7%) participants developed either esophageal, stomach, colorectal, biliary, pancreatic, or liver cancer.

Compared with non-drinkers, the risk of GI cancer was higher for:

  • Mild drinkers: aHR 1.04 (95% CI 1.03-1.05)
  • Moderate drinkers: aHR 1.14 (95% CI 1.12-1.15)
  • Heavy drinkers: aHR 1.28 (95% CI 1.26-1.29)

Risk patterns were similar among the different GI cancers, with the exception of liver cancer, which showed a decreased risk among mild drinkers (aHR 0.91, 95% CI 0.89-0.93), Shin and colleagues noted.

The authors acknowledged the study had limitations, including the fact that they obtained alcohol consumption data based on self-administered questionnaires, which raised the possibility of under-reporting of consumption. In addition, their use of administrative data meant that they did not have participants' clinical information, such as cancer histologic characteristics.

Shin and colleagues also noted that many Koreans have an inactive form of aldehyde dehydrogenase (ALDH2 [OMIM 100650]), which encodes a major enzyme responsible for alcohol metabolism that eliminates acetaldehyde. These individuals may be more susceptible to the carcinogenic effects of alcohol, but also may tend to avoid consumption due to several reactions after drinking.

"However, this study is based on data that were not originally designed for studying alcohol consumption; thus, we were not able to assess aldehyde dehydrogenase gene status among participants or identify major differences in the biology of Korean binge drinkers. Therefore, caution is required when applying our results to other ethnic groups," the authors wrote.

In his commentary, Potter suggested that "it is worthwhile to ask whether some of the differences in patterns of consumption seen in this cohort are associated with the ALDH2 polymorphism."

"If there are, indeed, major differences in the biology of Korean binge drinkers, it may not be possible to make easy recommendations about drinking patterns, even in Korea, until there is a better understanding of the nature of behavioral and biological influences on drinking," Potter wrote.

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