Inherited variation at chromosome 12p13.33 including RAD52 influences squamous cell lung carcinoma risk
Menée sur 5 355 cas de cancer du poumon associé au tabagisme et 4 344 témoins fumeurs en population européenne, cette étude d'association sur le génome entier identifie un locus de susceptibilité au carcinome épidermoïde pulmonaire sur le chromosome 12p13.33
While lung cancer is largely caused by tobacco smoking, inherited genetic factors play a role in its etiology. Genome-wide association studies (GWAS) in Europeans have robustly demonstrated only three polymorphic variations influencing lung cancer risk. Tumor heterogeneity may have hampered the detection of association signal when all lung cancer subtypes were analyzed together. In a GWAS of 5,355 European smoking lung cancer cases and 4,344 smoking controls, we conducted a pathway-based analysis in lung cancer histologic subtypes with 19,082 SNPs mapping to 917 genes in the HuGE-defined "inflammation" pathway. We identified a susceptibility locus for squamous cell lung carcinoma (SQ) at 12p13.33 (RAD52, rs6489769), and replicated the association in three independent samples totaling 3,359 SQ cases and 9,100 controls (odds ratio=1.20, Pcombined=2.3×10-8). Significance: The combination of pathway-based approaches and information on disease specific subtypes can improve the identification of cancer susceptibility loci in heterogeneous diseases.