A Large-Scale Genome-Wide Gene-Gene Interaction Study of Lung Cancer Susceptibility in Europeans With a Trans-Ethnic Validation in Asians

作者：Ruyang Zhang, Sipeng Shen, Yongyue Wei, Ying Zhu, Yi Li, Jiajin Chen, Jinxing Guan, Zoucheng Pan, Yuzhuo Wang, Meng Zhu, Junxing Xie, Xiangjun Xiao, Dakai Zhu, Yafang Li, Demetrius Albanes, Maria Teresa Landi, Neil E. Caporaso, Stephen Lam, Adonina Tardón, Chu Chen, Stig E. Bojesen, Mattias Johansson, Angela Risch, Heike Bickeböller, H‐Erich Wichmann, Gad Rennert, Susanne M. Arnold, Paul Brennan, James McKay, John K. Field, Sanjay Shete, Loı̈c Le Marchand, Geoffrey Liu, Angeline S. Andrew, Lambertus A. Kiemeney, Shan Zienolddiny-Narui, Annelie Behndig, Mikael Johansson, Angela Cox, Philip Lazarus, Matthew B. Schabath, Melinda C. Aldrich, Juncheng Dai, Hongxia Ma, Yang Zhao, Zhibin Hu, Rayjean J. Hung, Christopher I. Amos, Hongbing Shen, Feng Chen, David C. Christiani · 发表于：Journal of Thoracic Oncology · 年份：2022 · DOI：10.1016/j.jtho.2022.04.011 · 被引用次数：42 · 研究领域：Genetic Associations and Epidemiology、Lung Cancer Treatments and Mutations、BRCA gene mutations in cancer

Introduction Although genome-wide association studies have been conducted to investigate genetic variation of lung tumorigenesis, little is known about gene-gene (G × G) interactions that may influence the risk of non-small cell lung cancer (NSCLC). Methods Leveraging a total of 445,221 European-descent participants from the International Lung Cancer Consortium OncoArray project, Transdisciplinary Research in Cancer of the Lung and UK Biobank, we performed a large-scale genome-wide G × G interaction study on European NSCLC risk by a series of analyses. First, we used BiForce to evaluate and rank more than 58 billion G × G interactions from 340,958 single-nucleotide polymorphisms (SNPs). Then, the top interactions were further tested by demographically adjusted logistic regression models. Finally, we used the selected interactions to build lung cancer screening models of NSCLC, separately, for never and ever smokers. Results With the Bonferroni correction, we identified eight statistically significant pairs of SNPs, which predominantly appeared in the 6p21.32 and 5p15.33 regions (e.g., rs521828 C6orf10 and rs204999 PRRT1 , OR interaction = 1.17, p = 6.57 × 10 −13 ; rs3135369 BTNL2 and rs2858859 HLA-DQA1 , OR interaction = 1.17, p = 2.43 × 10 −13 ; rs2858859 HLA-DQA1 and rs9275572 HLA-DQA2 , OR interaction = 1.15, p = 2.84 × 10 −13 ; rs2853668 TERT and rs62329694 CLPTM1L , OR interaction = 0.73, p = 2.70 × 10 −13 ). Notably, even with much genetic heterogeneity across ethniciti...