# High Circulating Platelet Count as a Risk Factor for Lung Squamous Cell Carcinoma: A Retrospective Study and Mendelian Randomization Analysis

## TL;DR

High platelet counts are linked to a higher risk of lung squamous cell carcinoma, suggesting a potential new risk factor for this cancer type.

## Contribution

This study is the first to report a causal effect of high platelet count on lung squamous cell carcinoma.

## Key findings

- Elevated platelet count is associated with increased odds of lung squamous cell carcinoma (OR = 1.63).
- Mendelian randomization analysis supports a causal relationship between high platelet count and LUSC.
- Age and five other hematological parameters are independent risk factors for lung cancer or LUSC.

## Abstract

The association between platelet count (PLTC) and the risk of lung squamous cell carcinoma (LUSC) remains unclear.

We analyzed 19 223 samples from public and internal cohorts to investigate the relationship between high PLTC and the risk of developing LUSC using the retrospective analysis and Mendelian randomization analysis (MRA).

Elevated PLTC were detected in the population with lung cancer compared to healthy individuals (odds ratio [OR] = 1.41 [per 1‐SD], 95% CI 1.13–1.75, p < 0.05). Furthermore, there is a significant association between elevated PLTC and an increased risk of LUSC based on an in‐house cohort (OR = 1.63 [per 1‐SD], 95% CI 1.08–2.45, p < 0.05). Individuals with high PLTC had an increased risk of developing LUSC using the inverse‐variance weighting method (OR = 1.62 [per 1‐SD], 95% CI 1.14–2.31, p < 0.05), an outcome that was directionally consistent across the weighted median, MR Egger, simple mode, and weighted modes methods (OR > 1.00). No pleiotropy (the MRA pleiotropy residual sum and outlier test p = 0.553) or heterogeneity (Cochran's Q statistic p = 0.777) was found in the MRAs. Besides PLTC, age and five other hematological parameters (e.g., red blood cell count) were identified as independent factors associated with the incidence of lung cancer or its subtype LUSC (p < 0.05).

High circulating PLTC may serve as a risk factor for lung squamous cell carcinoma.

A significant association was observed between genetically elevated platelet count and an increased risk of lung cancer and lung squamous cell carcinoma, based on the large sample sizes from the NHANES and in‐house cohorts.Furthermore, our results indicate a causal effect of high platelet count on the occurrence of lung squamous cell carcinoma, which, to the best of our knowledge, has not been previously reported.

A significant association was observed between genetically elevated platelet count and an increased risk of lung cancer and lung squamous cell carcinoma, based on the large sample sizes from the NHANES and in‐house cohorts.

Furthermore, our results indicate a causal effect of high platelet count on the occurrence of lung squamous cell carcinoma, which, to the best of our knowledge, has not been previously reported.