Haplotype and Cell Proliferation Analyses of Candidate Lung Cancer Susceptibility Genes on Chromosome 15q24-25.1
作者： Yan Liu , Pengyuan Liu , Weidong Wen , Michael A. James , Yian Wang
DOI: 10.1158/0008-5472.CAN-09-1833
关键词:
摘要: Recent genome-wide association studies have linked the chromosome 15q24-25.1 locus to nicotine addiction and lung cancer susceptibility. To refine locus, we performed a haplotype-based analysis of 194 familial cases 219 cancer-free controls from Genetic Epidemiology Lung Cancer Consortium (GELCC) collection, used proliferation apoptosis analyses determine which gene(s) in mediates effects on cell growth vitro. We identified two distinct subregions, hapL (P = 3.20 x 10(-6)) hapN 1.51 10(-6)), were significantly associated with cancer. encompasses IREB2, LOC123688, PSMA4, three nicotinic acetylcholine receptor subunit genes CHRNA5, CHRNA3, CHRNB4. Examination around revealed that PSMA4 plays role promoting proliferation. mRNA levels increased tumors compared normal tissues. Down-regulation expression decreased proteasome activity induced apoptosis. Proteasome dysfunction leads many diseases including cancer, drugs inhibit show promise as form treatment. Genes also investigated, but did not any direct effect concluded is strong candidate mediator growth, may directly affect susceptibility through its modulation
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