RGD Reference Report - Genetic variation in the TNF/TRAF2/ASK1/p38 kinase signaling pathway as markers for postoperative pulmonary complications in lung cancer patients. - Rat Genome Database

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Genetic variation in the TNF/TRAF2/ASK1/p38 kinase signaling pathway as markers for postoperative pulmonary complications in lung cancer patients.

Authors: Hildebrandt, MA  Roth, JA  Vaporciyan, AA  Pu, X  Ye, Y  Correa, AM  Kim, JY  Swisher, SG  Wu, X 
Citation: Hildebrandt MA, etal., Sci Rep. 2015 Jul 13;5:12068. doi: 10.1038/srep12068.
RGD ID: 11521299
Pubmed: PMID:26165383   (View Abstract at PubMed)
PMCID: PMC4499815   (View Article at PubMed Central)
DOI: DOI:10.1038/srep12068   (Journal Full-text)

Post-operative pulmonary complications are the most common morbidity associated with lung resection in non-small cell lung cancer (NSCLC) patients. The TNF/TRAF2/ASK1/p38 kinase pathway is activated by stress stimuli and inflammatory signals. We hypothesized that genetic polymorphisms within this pathway may contribute to risk of complications. In this case-only study, we genotyped 173 germline genetic variants in a discovery population of 264 NSCLC patients who underwent a lobectomy followed by genotyping of the top variants in a replication population of 264 patients. Complications data was obtained from a prospective database at MD Anderson. MAP2K4:rs12452497 was significantly associated with a decreased risk in both phases, resulting in a 40% reduction in the pooled population (95% CI:0.43-0.83, P = 0.0018). In total, seven variants were significant for risk in the pooled analysis. Gene-based analysis supported the involvement of TRAF2, MAP2K4, and MAP3K5 as mediating complications risk and a highly significant trend was identified between the number of risk genotypes and complications risk (P = 1.63 x 10(-8)). An inverse relationship was observed between association with clinical outcomes and complications for two variants. These results implicate the TNF/TRAF2/ASK1/p38 kinase pathway in modulating risk of pulmonary complications following lobectomy and may be useful biomarkers to identify patients at high risk.



RGD Manual Disease Annotations    Click to see Annotation Detail View

  
Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
MAP2K4Humanlung non-small cell carcinoma amelioratesIAGP associated with Postoperative Complications and DNA:SNP:intron: (rs12452497)(human)RGD 
Map2k4Ratlung non-small cell carcinoma amelioratesISOMAP2K4 (Homo sapiens)associated with Postoperative Complications and DNA:SNP:intron: (rs12452497)(human)RGD 
Map2k4Mouselung non-small cell carcinoma amelioratesISOMAP2K4 (Homo sapiens)associated with Postoperative Complications and DNA:SNP:intron: (rs12452497)(human)RGD 

Phenotype Annotations    Click to see Annotation Detail View

Manual Human Phenotype Annotations - RGD

Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
MAP2K4HumanNon-small cell lung carcinoma amelioratesIAGP DNA:SNP:intron: (rs12452497)(human)RGD 
Objects Annotated

Genes (Rattus norvegicus)
Map2k4  (mitogen activated protein kinase kinase 4)

Genes (Mus musculus)
Map2k4  (mitogen-activated protein kinase kinase 4)

Genes (Homo sapiens)
MAP2K4  (mitogen-activated protein kinase kinase 4)


Additional Information