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Fact or fiction: Alcohol increases lung cancer risk?

Fact or fiction: Alcohol increases lung cancer risk?

MDLinx

By Naveed Saleh, MD, MS, for MDLinx

February 4, 2020

In recent years, research has emerged on the link between alcohol use and lung cancer. But, the results, by and large, have been mixed. While some researchers have demonstrated an inverse correlation between alcohol consumption and lung cancer, others have shown quite the opposite. In fact, University of Liverpool researchers recently found that alcohol consumption may be causally related to several lung cancer outcomes.

So, what gives? Why all the confusion and inconclusivity? It seems that it may all boil down to the amount of alcohol consumed.

The WHO notes that the “harmful use of alcohol is a causal factor in more than 200 diseases and injury conditions.” Excessive alcohol consumption involves interactions between complicated genetic and nongenetic risk factors. Likewise, lung cancer involves a gamut of quantifiable/unquantifiable lifestyle and environmental factors.

A causal relationship

Some researchers have identified excessive alcohol use as a causal risk factor for the development of lung cancer.

For instance, in the study conducted by the University of Liverpool researchers, they performed a genetic correlation analysis to determine genetic and non-genetic (lifestyle and demographic) factors associated with extreme alcohol use in white British individuals from the UK Biobank. After controlling for confounders, the factors most strongly correlated with excessive alcohol consumption included smoking variables (“ever” vs “never” smoked) and lung cancer outcomes (eg, squamous cell cancer and other lung cancer).

Importantly, repeat genome-wide association studies (GWAS) analysis and Mendelian randomization (MR), in which smoking status was stratified (“ever smoking” vs “never smoking”), consistently demonstrated an association with lung cancer.

The authors surmised that heavy alcohol consumption may be a modifiable risk factor in the prevention of lung cancer.

“Determining alcohol’s contribution to lung cancer often has been limited by the strong positive correlation between alcohol intake and smoking. However, the outcomes from the MR provide potential evidence of a causal relationship in our overall sample and when stratified by smoking status,” wrote the authors.

“Lung cancer is a complex and multifactorial disease involving genetic and a range of measurable and nonmeasurable environmental and lifestyle factors. Hence, heavy alcohol consumption is one potentially modifiable risk factor to reduce disease incidence,” they added.

Other studies

Further supporting the alcohol-lung cancer link are findings from the Environment and Genetics in Lung Cancer Etiology (EAGLE) study. In this population-based case-control study, Italian researchers investigated the correlation between alcohol use and lung cancer risk in over 4,000 participants. Specifically, between 2002 and 2005, they matched 2,100 patients with primary lung cancer with 2,120 randomly selected control patients. Furthermore, alcohol use in adulthood was assessed in 1,855 patients and 2,065 controls.

Overall, the researchers found an increased risk of lung cancer in both non-drinkers (OR: 1.42, 95% CI: 1.03-2.01) and excessive drinkers (≥ 60 g/day; OR:1.44, 95% CI: 1.01-2.07) but not in light drinkers (0.1-4.9 g/day). The impact of alcohol on lung cancer risk was modified by smoking behavior, with no excess risk exhibited by never smokers.

“[H]eavy alcohol consumption was a risk factor for lung cancer among smokers in this study,” the authors concluded. “Although residual confounding by tobacco smoking can never be completely ruled out, this finding may reflect a joint effect of alcohol and tobacco, emphasizing the need for improved strategies to help people reduce their alcohol consumption and quit smoking.”

Finally, in a high-powered pooled analysis incorporating results from the International Lung Cancer Consortium and SYNERGY study, researchers observed a J-shaped association between alcohol intake and lung cancer, which was most notable for beer intake and squamous cell lung cancer.

Potential mechanisms

The mechanisms delineating any relationship between alcohol consumption and lung cancer risk remain to be elucidated. Nevertheless, some experts suggest that while low levels of alcohol trigger the beating of cilia of mucociliary epithelium, excessive tippling leads to progressive desensitization of ciliary response, thus attenuating the defense mechanisms that protect the lung from pollutants, allergens, and pathogens.

Furthermore, chronic alcohol intake could interfere with the immune response against pathogens by reducing the phagocytic capabilities of macrophages, thus resulting in the release of pro-inflammatory cytokines.

Food for thought

It bears repeating that results from studies examining whether alcohol consumption is linked to lung cancer have been mixed—with some findings supporting an inverse association. Nevertheless, other experts (such as those discussed above) have suggested that alcohol intake is a modifiable risk factor for disease prevention—food for thought when seeing patients.