期刊
JOURNAL OF CANCER
卷 11, 期 5, 页码 1075-1081出版社
IVYSPRING INT PUBL
DOI: 10.7150/jca.35127
关键词
lung cancer; single-nucleotide polymorphisms (SNPs); chromatin interactions; Genome-wide association studies (GWAS); expression quantitative trait loci
类别
资金
- National Key RD Program [2017YFC0907905]
- National Natural Science of China [81922061, 81973123, 81521004, 81820108028, 81703295]
- Innovation of Graduate Student Training Project in Jiangsu Province [KYCX17_1260]
- Priority Academic Program for the Development of Jiangsu Higher Education Institutions [Public Health and Preventive Medicine]
- Top-notch Academic Programs Project of Jiangsu Higher Education Institutions [PPZY2015A067]
Genome-wide association studies (GWAS) have reported 45 single-nucleotide polymorphisms (SNPs) that may contribute to the susceptibility of lung cancer, with the majority in non-coding regions. However, no study has ever systematically evaluated the association between SNPs in physical chromatin interaction regions and lung cancer risk. In this study, we integrated the chromatin interaction information (Hi-C data) of lung cancer cell line and conducted a meta-analysis with two Asian GWASs (7,127 cases and 6,818 controls) to evaluate the association of potentially functional SNPs in chromatin interaction regions with lung cancer risk. We identified four novel lung cancer susceptibility loci located at 1q21.1 (rs17160062, P=4.00x10(-6), 2p23.3 (rs670343, P=4.87x10(-7)), 2p15 (rs9309336, P=3.24x10(-6)) and 17q21.2 (rs9252, P= 1.51 x10(-5)) that were significantly associated with lung cancer risk after correction for multiple tests. Functional annotation result indicated that these SNPs may contribute to the development of lung cancer by affecting the availability of transcription factor binding sites. The HaploReg analysis suggested that rs9309336 may affect binding motif of transcription factor Foxpl. Expression quantitative trait loci analysis revealed that rs9309336 and rs17160062 could regulate the expressions of cancer-related genes (PUS10 and CHD1L). Our results revealed that variants in chromatin interaction regions could contribute to the development of lung cancer by regulating the expression of target genes, which providing novel implications for the understanding of functional variants in the development of lung cancer.
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