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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.

ABSTRACT: 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 × 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.

SUBMITTER: Hildebrandt MA

PROVIDER: S-EPMC4499815 | biostudies-literature | 2015 Jul

REPOSITORIES: biostudies-literature

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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.

Hildebrandt Michelle A T MA Roth Jack A JA Vaporciyan Ara A AA Pu Xia X Ye Yuanqing Y Correa Arlene M AM Kim Jae Y JY Swisher Stephen G SG Wu Xifeng X

Scientific reports 20150713

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 ...[more]

PMID: 26165383

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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.

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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.

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