Modifiable factors for benign salivary gland neoplasms: A Mendelian randomization study

Observational studies have found associations between smoking, alcohol, radiation, body mass index (BMI), periodontitis, and the hazard of benign salivary gland neoplasms (BSGNs). Nevertheless, the etiology of BSGNs remains unclear. This study aims to assess the causal association between these modifiable factors and the BSGNs.

Genetic instruments associated with exposures at the genome-wide significance level were selected from corresponding genome-wide association studies. The summary statistics for BSGNs were obtained from the FinnGen consortium (2445 cases and 340,054 controls). The inverse variance-weighted method was used as the primary analysis, and several sensitivity analyses were performed to test the reliability.

Genetically predicted higher lifetime smoking index (odds ratio [OR] = 2.10, p = 0.012) and BMI (OR = 1.58, p = 2.29 × 10^-5) were associated with elevated risk of BSGNs, whereas other exposures do not. Sensitivity analyses showed consistency. The causal effect of the lifetime smoking index became more significant after adjusting for BMI (OR = 2.89, p = 0.005) and alcohol consumption (OR = 2.49, p = 0.002). A slight negative association emerged for alcohol consumption with adjustment for cigarettes per day (OR = 0.53, p = 0.034) but disappeared when adjusting for cigarettes per day and BMI.

This study supports the independent causal role of lifetime smoking index and BMI in BSGNs risk.