A Genome-Wide Association Study of Small Cell Lung Cancer

Abstract

Introduction: Small cell lung cancer (SCLC) comprises 10-15% of all lung cancer cases and is the most aggressive histological type. Survival is poor and the molecular landscape of this disease is extraordinarily complex. The objective of this paper was to perform a Genome-Wide Association Study (GWAS) of this disease using a case-control study specifically designed for small cell lung cancer (SCLC).

Methods: Incident cases were consecutively recruited from 8 hospitals from different regions of Spain. Controls were recruited from the same hospitals using a frequency sampling based on age and sex distribution of cases. Biological samples were obtained along with detailed information on cases and controls lifestyle, including tobacco and radon exposure.

Results: We included 271 SCLC cases and 557 controls. We found evidence (p-values<10^-5) of an association in the complete dataset for several loci, while MAP4 showed a significant association in the gene-based analysis. Pathway analysis suggested that ATR, ATRIP, MCM4, MCM5, ORC4, RPA3 and CDC25A genes have a role on the onset of SCLC.

Conclusion: This study provides biological evidence for pathways related to SCLC, offering novel loci for further research.

Keywords: Case–control study; Genome-Wide Association Study; Genomics; Small cell lung cancer.