Inherited variation at chromosome 12p13.33, including RAD52, influences the risk of squamous cell lung carcinoma

Jianxin Shi, Nilanjan Chatterjee, Melissa Rotunno, Yufei Wang, Angela C. Pesatori, Dario Consonni, Peng Li, William Wheeler, Peter Broderick, Marc Henrion, Timothy Eisen, Zhaoming Wang, Wei Chen, Qiong Dong, Demetrius Albanes, Michael Thun, Margaret R. Spitz, Pier Alberto Bertazzi, Neil E. Caporaso, Stephen J. ChanockChristopher I. Amos, Richard S. Houlston, Maria Teresa Landi

Research output: Contribution to journalArticlepeer-review

49 Scopus citations


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.

Original languageEnglish
Pages (from-to)131-139
Number of pages9
JournalCancer Discovery
Issue number2
StatePublished - Feb 2012
Externally publishedYes


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