Association of neutrophil count with lung cancer risk and prognosis: A Mendelian randomization and NHANES analysis

Neutrophil count is closely related to the development of various tumors. This study aimed to assess the impact of neutrophil count on lung cancer incidence and survival. Genetic variants associated with neutrophil count were selected as instrumental variables from genome-wide association study data, and the causal relationship between the neutrophil count and lung cancer risk was assessed using Mendelian randomization (MR) analysis. Separately, survival analysis was used to assess the effect of neutrophil count on survival in adults with lung cancer using data from the National Health and Nutrition Examination Survey database. Eleven single-nucleotide polymorphisms were used as instrumental variables to assess the effect of neutrophil count. MR analysis showed that elevated neutrophil counts were associated with a significantly reduced risk of lung cancer (odds ratio: 0.77, 95% confidence interval [CI]: 0.62-0.95, P = .017) and lung adenocarcinoma (odds ratio: 0.63, 95% CI: 0.45-0.87, P = .005). Conversely, Kaplan-Meier survival analysis showed that a low neutrophil count was associated with significantly longer overall survival in individuals with lung cancer than a high neutrophil count (hazard ratio [HR]: 0.53, 95% CI: 0.31-0.90, P = .017). Cox regression revealed a significant interaction between a high neutrophil count and age (P = .003); the effect of a high neutrophil count on prognosis was significant in adults aged under 65 years (HR: 0.21, 95% CI: 0.10-0.47, P < .001) but a high neutrophil count was not associated with prognosis in adults aged 65 years and older (HR: 1.17, 95% CI: 0.57-2.39, P = .671). MR analysis revealed that neutrophil count plays a causal role in protecting against lung cancer, whereas survival analysis revealed that, in individuals with lung cancer, a higher neutrophil count is associated with a worse prognosis. The specific pathogenic mechanisms by which neutrophils affect lung cancer development and prognosis warrant further study.