| 1. |
- Ji, Xuemei, et al.
(författare)
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Identification of susceptibility pathways for the role of chromosome 15q25.1 in modifying lung cancer risk
- 2018
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Ingår i: Nature Communications. - : NATURE PUBLISHING GROUP. - 2041-1723. ; 9, s. 1-15
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Tidskriftsartikel (refereegranskat)abstract
- Genome-wide association studies (GWAS) identified the chromosome 15q25.1 locus as a leading susceptibility region for lung cancer. However, the pathogenic pathways, through which susceptibility SNPs within chromosome 15q25.1 affects lung cancer risk, have not been explored. We analyzed three cohorts with GWAS data consisting 42,901 individuals and lung expression quantitative trait loci (eQTL) data on 409 individuals to identify and validate the underlying pathways and to investigate the combined effect of genes from the identified susceptibility pathways. The KEGG neuroactive ligand receptor interaction pathway, two Reactome pathways, and 22 Gene Ontology terms were identified and replicated to be significantly associated with lung cancer risk, with P values less than 0.05 and FDR less than 0.1. Functional annotation of eQTL analysis results showed that the neuroactive ligand receptor interaction pathway and gated channel activity were involved in lung cancer risk. These pathways provide important insights for the etiology of lung cancer.
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| 2. |
- Li, Yafang, et al.
(författare)
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Genome-wide interaction study of smoking behavior and non-small cell lung cancer risk in Caucasian population
- 2018
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Ingår i: Carcinogenesis. - : Oxford University Press (OUP). - 0143-3334 .- 1460-2180. ; 39:3, s. 336-346
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Tidskriftsartikel (refereegranskat)abstract
- Non-small cell lung cancer is the most common type of lung cancer. Both environmental and genetic risk factors contribute to lung carcinogenesis. We conducted a genome-wide interaction analysis between single nucleotide polymorphisms (SNPs) and smoking status (never- versus ever-smokers) in a European-descent population. We adopted a two-step analysis strategy in the discovery stage: we first conducted a case-only interaction analysis to assess the relationship between SNPs and smoking behavior using 13 336 non-small cell lung cancer cases. Candidate SNPs with P-value <0.001 were further analyzed using a standard case-control interaction analysis including 13 970 controls. The significant SNPs with P-value <3.5 × 10-5 (correcting for multiple tests) from the case-control analysis in the discovery stage were further validated using an independent replication dataset comprising 5377 controls and 3054 non-small cell lung cancer cases. We further stratified the analysis by histological subtypes. Two novel SNPs, rs6441286 and rs17723637, were identified for overall lung cancer risk. The interaction odds ratio and meta-analysis P-value for these two SNPs were 1.24 with 6.96 × 10-7 and 1.37 with 3.49 × 10-7, respectively. In addition, interaction of smoking with rs4751674 was identified in squamous cell lung carcinoma with an odds ratio of 0.58 and P-value of 8.12 × 10-7. This study is by far the largest genome-wide SNP-smoking interaction analysis reported for lung cancer. The three identified novel SNPs provide potential candidate biomarkers for lung cancer risk screening and intervention. The results from our study reinforce that gene-smoking interactions play important roles in the etiology of lung cancer and account for part of the missing heritability of this disease.
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| 3. |
- Ferreiro-Iglesias, Aida, et al.
(författare)
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Fine mapping of MHC region in lung cancer highlights independent susceptibility loci by ethnicity
- 2018
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Ingår i: Nature Communications. - : Nature Publishing Group. - 2041-1723. ; 9
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Tidskriftsartikel (refereegranskat)abstract
- Lung cancer has several genetic associations identified within the major histocompatibility complex (MHC); although the basis for these associations remains elusive. Here, we analyze MHC genetic variation among 26,044 lung cancer patients and 20,836 controls densely genotyped across the MHC, using the Illumina Illumina OncoArray or Illumina 660W SNP microarray. We impute sequence variation in classical HLA genes, fine-map MHC associations for lung cancer risk with major histologies and compare results between ethnicities. Independent and novel associations within HLA genes are identified in Europeans including amino acids in the HLA-B*0801 peptide binding groove and an independent HLA-DQB1*06 loci group. In Asians, associations are driven by two independent HLA allele sets that both increase risk in HLA-DQB1*0401 and HLA-DRB1*0701; the latter better represented by the amino acid Ala-104. These results implicate several HLA-tumor peptide interactions as the major MHC factor modulating lung cancer susceptibility.
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| 4. |
- Scheitz, Jan F, et al.
(författare)
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Cohort profile: Thrombolysis in Ischemic Stroke Patients (TRISP): a multicentre research collaboration.
- 2018
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Ingår i: BMJ open. - : BMJ. - 2044-6055. ; 8:9
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Tidskriftsartikel (refereegranskat)abstract
- The ThRombolysis in Ischemic Stroke Patients (TRISP) collaboration aims to address clinically relevant questions about safety and outcomes of intravenous thrombolysis (IVT) and endovascular thrombectomy. The findings can provide observational information on treatment of patients derived from everyday clinical practice.TRISP is an open, investigator-driven collaborative research initiative of European stroke centres with expertise in treatment with revascularisation therapies and maintenance of hospital-based registries. All participating centres made a commitment to prospectively collect data on consecutive patients with stroke treated with IVT using standardised definitions of variables and outcomes, to assure accuracy and completeness of the data and to adapt their local databases to answer novel research questions.Currently, TRISP comprises 18 centres and registers >10 000 IVT-treated patients. Prior TRISP projects provided evidence on the safety and functional outcome in relevant subgroups of patients who were excluded, under-represented or not specifically addressed in randomised controlled trials (ie, pre-existing disability, cervical artery dissections, stroke mimics, prior statin use), demonstrated deficits in organisation of acute stroke care (ie, IVT during non-working hours, effects of onset-to-door time on onset-to-needle time), evaluated the association between laboratory findings on outcome after IVT and served to develop risk estimation tools for prediction of haemorrhagic complications and functional outcome after IVT.Further TRISP projects to increase knowledge of the effect and safety of revascularisation therapies in acute stroke are ongoing. TRISP welcomes participation and project proposals of further centres fulfilling the outlined requirements. In the future, TRISP will be extended to include patients undergoing endovascular thrombectomy.
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