Although lung cancer is largely caused by tobacco smoking, inherited genetic factors play a role in its etiology. Genome-wide association studies in Europeans have only robustly demonstrated 3 polymorphic variations that influence the risk of lung cancer. Tumor heterogeneity may have hampered the detection of association signal when all lung cancer subtypes were analyzed together. In a genome-wide association study of 5,355 European ever-smoker lung cancer patients and 4,344 smoking control subjects, we conducted a pathway-based analysis in lung cancer histologic subtypes with 19,082 single-nucleotide polymorphisms mapping to 917 genes in the HuGE-defined "inflammation" pathway. We identified a susceptibility locus for squamous cell lung carcinoma at 12p13.33 (RAD52, rs6489769) and replicated the association in 3 independent studies totaling 3,359 squamous cell lung carcinoma cases and 9,100 controls (OR = 1.20, P(combined) = 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
Inherited variation at chromosome 12p13.33, including RAD52, influences the risk of squamous cell lung carcinoma risk / J. Shi, N. Chatterjee, M. Rotunno, Y. Wang, A.C. Pesatori, D. Consonni, P. Li, W. Wheeler, P. Broderick, M. Henrion, T. Eisen, Z. Wang, W. Chen, Q. Dong, D. Albanes, M. Thun, M.R. Spitz, P.A. Bertazzi, N.E. Caporaso, S.J. Chanock, C.I. Amos, R.S. Houlston, M.T. Landi. - In: CANCER DISCOVERY. - ISSN 2159-8274. - 2:2(2012 Feb), pp. 131-139. [10.1158/2159-8290.CD-11-0246]
Inherited variation at chromosome 12p13.33, including RAD52, influences the risk of squamous cell lung carcinoma risk
A.C. Pesatori;P.A. Bertazzi;
2012
Abstract
Although lung cancer is largely caused by tobacco smoking, inherited genetic factors play a role in its etiology. Genome-wide association studies in Europeans have only robustly demonstrated 3 polymorphic variations that influence the risk of lung cancer. Tumor heterogeneity may have hampered the detection of association signal when all lung cancer subtypes were analyzed together. In a genome-wide association study of 5,355 European ever-smoker lung cancer patients and 4,344 smoking control subjects, we conducted a pathway-based analysis in lung cancer histologic subtypes with 19,082 single-nucleotide polymorphisms mapping to 917 genes in the HuGE-defined "inflammation" pathway. We identified a susceptibility locus for squamous cell lung carcinoma at 12p13.33 (RAD52, rs6489769) and replicated the association in 3 independent studies totaling 3,359 squamous cell lung carcinoma cases and 9,100 controls (OR = 1.20, P(combined) = 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 diseasesFile | Dimensione | Formato | |
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