Sensitivity to Environmental Stress and Adversity and Lung Cancer

Abstract

Importance: Sensitivity to environmental stress and adversity may influence lung cancer risk, highlighting a critical link between psychosocial factors and cancer etiology. Objective: To evaluate whether genetically estimated sensitivity to environmental stress and adversity is associated with lung cancer risk. Design, Setting, and Participants: Data were obtained from a genome-wide association study identifying 37 independent genetic variants strongly associated with sensitivity to environmental stress and adversity and a cross-ancestry genome-wide meta-analysis from the International Lung Cancer Consortium. Data were extracted between October 2023 and January 2024 and analyzed between February 2024 and June 2024. Exposures: Genetically estimated sensitivity to environmental stress and adversity. Main Outcomes and Measures: The main outcome was lung cancer risk, and odds ratios and 95% CIs were used to assess the association between sensitivity to environmental stress and adversity with lung cancer risk. This genetic association study used a 2-sample Mendelian randomization (MR) to estimate the association between genetically estimated sensitivity to environmental stress and adversity and lung cancer risk across different histologic types. Results: Using data from 351827 individuals from the UK Biobank and a cross-ancestry genome-wide analysis of 61047 lung cancer cases and 947237 controls from the International Lung Cancer Consortium, sensitivity to environmental stress and adversity was significantly associated with an increased risk of lung cancer among individuals of European ancestry (OR, 1.49; 95% CI, 1.13-1.98; P =.005) and in the cross-ancestry analysis (OR, 1.45; 95% CI, 1.13-1.85; P =.004). There were heterogeneities in the observed associations across histologic subtypes among different population ancestries. Among individuals of European ancestry, a significant association was noted among squamous cell carcinoma (OR, 1.69; 95% CI, 1.06-2.70; P =.03). Among individuals of East Asian ancestry, an increased risk was observed for adenocarcinoma (OR, 2.04; 95% CI, 1.00-4.18; P =.05). Associations were not observed across any of the 3 histologic subtypes among individuals of African ancestry. Conclusions and Relevance: In this genetic association study, sensitivity to environmental stress and adversity was associated with lung cancer risk. These results underscore the necessity for further research into the nuanced association between psychosocial stress and cancer risk, with a particular focus on diverse populations.