Hyo-Gyoung Kang1, Shin Yup Lee, Hyo-Sung Jeon, Yi Young Choi, Soyoun Kim, Won Kee Lee, Hyun Chul Lee, Jin Eun Choi, Eun Young Bae, Seung Soo Yoo, Jaehee Lee, Seung Ick Cha, Chang Ho Kim, Myung Hoon Lee, Young Tae Kim, Jin Hee Kim, Yun-Chul Hong, Yeul Hong Kim, Jae Yong Park. 1. *Department of Biochemistry and Cell Biology and †Department of Internal Medicine, School of Medicine, Kyungpook National University, Daegu, Korea; ‡Lung Cancer Center, Kyungpook National University Medical Center, Daegu, Korea; §Biostatistics Center, School of Medicine, Kyungpook National University, Daegu, Korea; ‖D&P Biotech, Inc., Daegu, Korea; ¶Department of Thoracic and Cardiovascular Surgery, Clinical Research Institute, Seoul National University Hospital, Seoul, Korea; #Genomic Medicine Institute, Cancer Research Institute, Seoul National University, Seoul, Korea; **Department of Environmental Health, Graduate School of Public Health, Seoul National University, Seoul, Korea; ††Department of Preventive Medicine, Seoul National University School of Medicine, Seoul, Korea; ‡‡Division of Oncology/Hematology, Department of Internal Medicine, College of Medicine, Korea University, Seoul, Korea; and §§Cancer Research Institute, Korea University, Seoul, Korea.
Abstract
INTRODUCTION: It has been estimated that the proportion of never-smokers among females with lung cancer is 53% worldwide and 75% in Korea. We conducted a two-stage study to identify genetic factors responsible for lung cancer susceptibility in female never-smokers. MATERIALS AND METHODS: In a discovery set, 1969 potentially functional single nucleotide polymorphisms (SNPs) of 1151 genes, which were related to cancer development and progression, were evaluated using the Affymetrix custom-made GeneChip in 181 female never-smokers with lung cancer and 179 controls. A replication study was performed on an independent cohort of 596 cases and 1194 healthy controls. RESULTS: Sixteen SNPs with p < 0.05 for genotype distribution in the discovery set were enrolled in the replication study. Among 16 SNPs, three SNPs (colony-stimulating factor 1 receptor [CSF1R] rs10079250A>G, tumor protein p63 [TP63] rs7631358G>A, and corepressor interacting with RBPJ 1 [CIR1] rs13009079T>C) were found to be significantly associated with lung cancer in the same direction as the discovery set. Homology-based model for CSF1R indicated that the rs10079250A>G leads to increased positive charge of CSF-binding region of CSF1R, thereby increasing the chance of binding between CSF and CSF1R. In addition, this SNP was found to increase the phosphorylation of a mitogen-activated protein kinase, JNK. CONCLUSIONS: Our results suggest that the three SNPs, particularly CSF1R rs10079250, may contribute to lung cancer susceptibility in never-smoking females.
INTRODUCTION: It has been estimated that the proportion of never-smokers among females with lung cancer is 53% worldwide and 75% in Korea. We conducted a two-stage study to identify genetic factors responsible for lung cancer susceptibility in female never-smokers. MATERIALS AND METHODS: In a discovery set, 1969 potentially functional single nucleotide polymorphisms (SNPs) of 1151 genes, which were related to cancer development and progression, were evaluated using the Affymetrix custom-made GeneChip in 181 female never-smokers with lung cancer and 179 controls. A replication study was performed on an independent cohort of 596 cases and 1194 healthy controls. RESULTS: Sixteen SNPs with p < 0.05 for genotype distribution in the discovery set were enrolled in the replication study. Among 16 SNPs, three SNPs (colony-stimulating factor 1 receptor [CSF1R] rs10079250A>G, tumor protein p63 [TP63] rs7631358G>A, and corepressor interacting with RBPJ 1 [CIR1] rs13009079T>C) were found to be significantly associated with lung cancer in the same direction as the discovery set. Homology-based model for CSF1R indicated that the rs10079250A>G leads to increased positive charge of CSF-binding region of CSF1R, thereby increasing the chance of binding between CSF and CSF1R. In addition, this SNP was found to increase the phosphorylation of a mitogen-activated protein kinase, JNK. CONCLUSIONS: Our results suggest that the three SNPs, particularly CSF1Rrs10079250, may contribute to lung cancer susceptibility in never-smoking females.
Authors: Tianhua Niu; Ning Liu; Xun Yu; Ming Zhao; Hyung Jin Choi; Paul J Leo; Matthew A Brown; Lei Zhang; Yu-Fang Pei; Hui Shen; Hao He; Xiaoying Fu; Shan Lu; Xiang-Ding Chen; Li-Jun Tan; Tie-Lin Yang; Yan Guo; Nam H Cho; Jie Shen; Yan-Fang Guo; Geoffrey C Nicholson; Richard L Prince; John A Eisman; Graeme Jones; Philip N Sambrook; Qing Tian; Xue-Zhen Zhu; Christopher J Papasian; Emma L Duncan; André G Uitterlinden; Chan Soo Shin; Shuanglin Xiang; Hong-Wen Deng Journal: J Bone Miner Res Date: 2015-09-11 Impact factor: 6.741