Association between asthma and melanoma: Results from the NHANES 2009-2016 and Mendelian randomization study

Abstract Objective: To investigate the phenotypic and genetic associations between asthma and melanoma. Methods: Initially, we conducted a cross-sectional study utilizing data sourced from the National Health and Nutrition Examination Survey (NHANES) spanning the years 2009 to 2016. In the survey, individuals answering "Yes" to "Ever been told you have asthma?" were categorized as asthma patients, while those answering "yes" to "Ever told you had cancer or malignancy?" and specifying "melanoma" were defined as melanoma patients. We employed a multivariate logistic regression model to evaluate the observed association between asthma and melanoma risk. Subsequently, the Mendelian randomization (MR) approach, a novel method minimizing bias and establishing causal relationships, was utilized asthma dataincluding childhood-onset (347,481 controls and 46,802 cases), adult-onset (347,481 controls and 9,676 cases), and overall onset (347,481 controls and 22,296 cases) were retrieved from GWAS databases, alongside melanoma data (32697 samples) obtained from the FinnGen. Two-sample MR analysis was conducted to evaluate the causal relationship between asthma and melanoma, with the Inverse Variance Weighting (IVW) method as the primary data analysis approach. Results: The observational study encompassed a total of 23,218 participants, including 129 melanoma patients. In the unadjusted multivariate logistic regression model, asthma was associated with a reduced risk of melanoma (odds ratio [OR] = 0.404, 95% confidence interval [CI] = 0.188-0.869, P=0.023). Similar results were observed after adjusting for gender, age, race, and education level (OR = 0.439, 95% CI = 0.209-0.922, P=0.034). However, further adjustments for variables such as BMI, poverty to income ratio, diabetes, alcohol use, smoking, hypertension, hyperlipidemia, and skin reaction to sun after non-exposure, outdoor time did not yield statistically significant results (OR = 0.675, 95% CI = 0.205-2.223, P=0.522). Mendelian analysis also failed to demonstrate a causal relationship between asthma and melanoma risk. Conclusion: While there may be an association between asthma and a reduced risk of melanoma, no causal relationship exists between the two. Further prospective studies with larger sample sizes are warranted to corroborate our findings.