A GENOME-WIDE ASSOCIATION STUDY IN A ROMANIAN LUNG CANCER COHORT IDENTIFIES MULTIPLE LOCI ASSOCIATED WITH SUSCEPTIBILITY TO RESPIRATORY TRACT INFECTIONS

Abstract

Introduction: Lung cancer ranks first in the incidence of cancer deaths worldwide. Respiratory tract infection complications appear often in patients with lung cancer and can ultimately be fatal. Objectives: We aim to identify genetic markers associated with lung cancer susceptibility using a genome-wide association study and evaluate the identified genetic markers in the context of associated lower respiratory tract infections in the Romanian population. Methods: The study cohort consisted of 1,092 unrelated histopathologically confirmed lung cancer (LC) cases and 1,073 control patients admitted for medical conditions, excluding cancer. The DNA was extracted from buccal swab samples and analyzed by deCODE Genetics (Reykjavik, Iceland). Results: We identified 49 unique variants from a systematic literature review for variants associated with LC using the NHGRI catalog database. Nine tested variants in the Romanian genome-wide association study (GWAS) reached a genome-wide significance (p-value lower than 5 × 10-8), and 34 markers reached p-values of 10-7. Six of the 49 previously reported LC-associated SNPs replicated in the study cohort at a p 0.05 (rs1051530, rs8034191 at 15q25.1, rs2602141 at 15q15.3, rs31489, rs4975616, and rs401681 at 5p15.33) but with ORs for lung cancer generally smaller than the NHGRI catalog reported data. A secondary association investigated the susceptibility to respiratory tract infections for individuals carrying genetic markers previously known to be involved in LC oncogenetic processes. Conclusions: We validated previously known lung cancer SNPs associated with lung cancer risk in the Romanian population.