New research from the United Kingdom has linked pulmonary function impairment with an increase in susceptibility for lung cancer.1
“Despite a substantial body of observational literature demonstrating an increased risk of lung cancer in individuals with pulmonary dysfunction, confounding by shared environmental risk factors and high co-occurrence of lung cancer and airflow obstruction created uncertainty regarding the causal nature of this relationship,” researchers wrote.
To investigate the relationship between pulmonary function and risk for cancer, the researchers conducted genome-wide association analyses for 29,266 lung cancer cases from the UK Biobank cohort and 56,450 controls for the International Lung Cancer Consortium.
They found that lung cancer was genetically correlated with reduced forced expiratory volume in one second (FEV1) and the ratio of FEV1 to forced vital capacity (FVC). More specifically, reduction FEV1 was associated with increased squamous cell carcinoma risk (odds ratio [OR], 1.51; 95% CI, 1.21-1.88). Additionally, reduced FEV1/FVC increased the risk for adenocarcinoma (OR, 1.17; 95% CI, 1.01-1.35) and for lung cancer among those who had never smoked (OR, 1.56; 95% CI, 1.05-2.30).
Further analyses showed that several “pulmonary function instruments,” including 73 novel variants, influenced lung tissue gene expression. For example, the researchers identified 7 genes that were significantly associated with lung cancer risk that displayed consistent directions of effect for pulmonary function and lung cancer risk, “whereby alleles associated with increased expression were associated with impaired FEV1 or FEV1/FVC and increased cancer risk.”
“As our understanding of the shared genetic and molecular pathways between lung cancer and pulmonary disease continues to evolve, identification of new susceptibility loci for pulmonary function and lung cancer risk may have important implications for future precision prevention and screening endeavors,” the researchers wrote. “Multiple genetic determinants of lung function are in pathways that contain druggable targets … which may open new avenues for chemoprevention or targeted therapies for lung cancers with an obstructive pulmonary etiology.”
Kachuri L, Johansson M, Rashkin SR, et al. Immune-mediated genetic pathways resulting in pulmonary function impairment increase lung cancer susceptibility. Nat Commun. 2020;11(1):27.