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A Functional Polymorphism in CSF1R Gene Is a Novel Susceptibility Marker for Lung Cancer among Never-Smoking Females

Authors
Kang, Hyo-GyoungLee, Shin YupJeon, Hyo-SungChoi, Yi YoungKim, SoyounLee, Won KeeLee, Hyun ChulChoi, Jin EunBae, Eun YoungYoo, Seung SooLee, JaeheeCha, Seung IckKim, Chang HoLee, Myung HoonKim, Young TaeKim, Jin HeeHong, Yun-ChulKim, Yeul HongPark, Jae Yong
Issue Date
11월-2014
Publisher
ELSEVIER SCIENCE INC
Keywords
Lung cancer; Polymorphism; Never-smokers
Citation
JOURNAL OF THORACIC ONCOLOGY, v.9, no.11, pp.1647 - 1655
Indexed
SCIE
SCOPUS
Journal Title
JOURNAL OF THORACIC ONCOLOGY
Volume
9
Number
11
Start Page
1647
End Page
1655
URI
https://scholar.korea.ac.kr/handle/2021.sw.korea/97022
DOI
10.1097/JTO.0000000000000310
ISSN
1556-0864
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.
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