TY - JOUR
T1 - Inherited variation at chromosome 12p13.33, including RAD52, influences the risk of squamous cell lung carcinoma
AU - Shi, Jianxin
AU - Chatterjee, Nilanjan
AU - Rotunno, Melissa
AU - Wang, Yufei
AU - Pesatori, Angela C.
AU - Consonni, Dario
AU - Li, Peng
AU - Wheeler, William
AU - Broderick, Peter
AU - Henrion, Marc
AU - Eisen, Timothy
AU - Wang, Zhaoming
AU - Chen, Wei
AU - Dong, Qiong
AU - Albanes, Demetrius
AU - Thun, Michael
AU - Spitz, Margaret R.
AU - Bertazzi, Pier Alberto
AU - Caporaso, Neil E.
AU - Chanock, Stephen J.
AU - Amos, Christopher I.
AU - Houlston, Richard S.
AU - Landi, Maria Teresa
PY - 2012/2
Y1 - 2012/2
N2 - 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, Pcombined = 2.3 × 10-8). SIGNIFICA NCE: The combination of pathway-based approaches and information on disease-specific subtypes can improve the identification of cancer susceptibility loci in heterogeneous diseases.
AB - 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, Pcombined = 2.3 × 10-8). SIGNIFICA NCE: The combination of pathway-based approaches and information on disease-specific subtypes can improve the identification of cancer susceptibility loci in heterogeneous diseases.
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U2 - 10.1158/2159-8290.CD-11-0246
DO - 10.1158/2159-8290.CD-11-0246
M3 - Article
C2 - 22585858
AN - SCOPUS:84864185989
SN - 2159-8274
VL - 2
SP - 131
EP - 139
JO - Cancer discovery
JF - Cancer discovery
IS - 2
ER -