RESUMO
Although genome-wide association studies have identified more than eighty genetic variants associated with non-small cell lung cancer (NSCLC) risk, biological mechanisms of these variants remain largely unknown. By integrating a large-scale genotype data of 15 581 lung adenocarcinoma (AD) cases, 8350 squamous cell carcinoma (SqCC) cases, and 27 355 controls, as well as multiple transcriptome and epigenomic databases, we conducted histology-specific meta-analyses and functional annotations of both reported and novel susceptibility variants. We identified 3064 credible risk variants for NSCLC, which were overrepresented in enhancer-like and promoter-like histone modification peaks as well as DNase I hypersensitive sites. Transcription factor enrichment analysis revealed that USF1 was AD-specific while CREB1 was SqCC-specific. Functional annotation and gene-based analysis implicated 894 target genes, including 274 specifics for AD and 123 for SqCC, which were overrepresented in somatic driver genes (ER = 1.95, P = 0.005). Pathway enrichment analysis and Gene-Set Enrichment Analysis revealed that AD genes were primarily involved in immune-related pathways, while SqCC genes were homologous recombination deficiency related. Our results illustrate the molecular basis of both well-studied and new susceptibility loci of NSCLC, providing not only novel insights into the genetic heterogeneity between AD and SqCC but also a set of plausible gene targets for post-GWAS functional experiments.
Assuntos
Humanos , Adenocarcinoma de Pulmão/genética , Carcinoma Pulmonar de Células não Pequenas/genética , Carcinoma de Células Escamosas/genética , Heterogeneidade Genética , Predisposição Genética para Doença , Estudo de Associação Genômica Ampla , Neoplasias Pulmonares/genética , Polimorfismo de Nucleotídeo ÚnicoRESUMO
[Objective]To study the tendency of hip fracture by analyzing morbidity factors to provide an basis for preventing the fracture.[Method]All of the case records of hip fractures treated at west china hospital between 2000-1 and 2005-12 were checked and 583 inpatients were selected for analysis.[Result]The major injury cause was fall in the old and female was more susceptible.High energy injury was the major cause in younger 50. Osteoporosis and fall contributed best to the hip fracture in elderly.Concomitant disease and environmental factors increased the risk.[Conclusion]Osteoporosis and fall contribute most to the hip fracture in elderly,accordingly,to prevent fall and osteoporosis is vital to the old.