Smoking Mediates Link Between Schizophrenia and Lung Cancer Risk

Although schizophrenia is associated with a significantly increased risk for lung cancer, this relationship is largely mediated by the number of cigarettes smoked per day, according to new research published in Frontiers in Psychiatry.

Previous studies have found that both major depressive disorder (MDD) and schizophrenia have been associated with an increased risk for cancer. Given the prevalence of nicotine addiction among individuals with severe depression and schizophrenia, researchers hypothesized that these disorders may be linked to lung cancer risk.

To evaluate the association between MDD and schizophrenia and lung cancer risk, the researchers conducted a 2-sample bidirectional/multivariable Mendelian randomization (MR) and mediation analysis on genome-wide association study (GWAS) data from 2 large European ancestry cohorts – the PGC and GSCAN consortiums. The primary exposures of interest were MDD and schizophrenia. The primary outcomes of interest included the risk for lung adenocarcinoma, squamous cell lung cancer, and the overall composite risk for lung cancer. The multivariable MR analyses considered 3 smoking-related behaviors: smoking initiation, pack years of smoking, and cigarettes smoked per day.

The GWAS databases comprised 500,199 individuals with MDD and 127,906 individuals with schizophrenia. Additionally, data on the risk for lung cancer were collected from a cohort of 27,209 individuals of European ancestry.

The researchers found that schizophrenia was associated with a significantly higher overall risk for lung cancer (odds ratio [OR], 1.144; 95% CI, 1.048-1.248; P =.003), but was not significantly associated with a greater risk of developing lung adenocarcinoma or squamous cell lung cancer.

After adjusting for smoking-related behaviors, the researchers no longer observed a significant relationship between lung schizophrenia and the risk for lung adenocarcinoma, squamous cell lung cancer, or overall lung cancer. In mediation analyses, the number of cigarettes smoked per day mediated the relationship between schizophrenia and overall lung cancer risk (OR, 1.185; 95% CI, 1.112-1.264; P =.021), with a mediation effect of 61%.

Additionally, no significant associations were observed between MDD and lung cancer risk.

These findings suggest that smoking largely mediates the relationship between schizophrenia and the overall risk for lung cancer. The researchers concluded, “Including smoking in the analysis reduced the explanatory power of schizophrenia for lung cancer risk, suggesting that smoking is a crucial causal factor in this relationship.”

The primary study limitation is the inclusion of data from predominantly European cohorts, which may reduce the generalizability of the findings.

This article originally appeared on Psychiatry Advisor