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Interleukin polymorphisms associated with overall survival, disease-free survival, and recurrence in non-small cell lung cancer patients.

ABSTRACT: Biomarkers based on germline DNA variations could have translational implications by identifying prognostic factors and sub-classifying patients to tailored, patient-specific treatment. To investigate the association between germline variations in interleukin (IL) genes and lung cancer outcomes, we genotyped 251 single nucleotide polymorphisms (SNPs) from 33 different IL genes in 651 non-small cell lung cancer (NSCLC) patients. Analyses were performed to investigate overall survival, disease-free survival, and recurrence. Our analyses revealed 24 different IL SNPs significantly associated with one or more of the lung cancer outcomes of interest. The GG genotype of IL16:rs7170924 was significantly associated with disease-free survival (HR?=?0.65; 95% CI 0.50-0.83) and was the only SNP that produced a false discovery rate (FDR) of modest confidence that the association is unlikely to represent a false-positive result (FDR?=?0.142). Classification and regression tree (CART) analyses were used to identify potential higher-order interactions. We restricted the CART analyses to the five SNPs that were significantly associated with multiple endpoints (IL1A:rs1800587, IL1B:rs1143634, IL8:s12506479, IL12A:rs662959, and IL13:rs1881457) and IL16:rs7170924 which had the lowest FDR. CART analyses did not yield a tree structure for overall survival; separate CART tree structures were identified for recurrence, based on three SNPs (IL13:rs1881457, IL1B:rs1143634, and IL12A:rs662959), and for disease-free survival, based on two SNPs (IL12A:rs662959 and IL16:rs7170924), which may suggest that these candidate IL SNPs have a specific impact on lung cancer progression and recurrence. These data suggest that germline variations in IL genes are associated with clinical outcomes in NSCLC patients.

SUBMITTER: Woods NT

PROVIDER: S-EPMC4475444 | biostudies-literature | 2015 Jun

REPOSITORIES: biostudies-literature

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Interleukin polymorphisms associated with overall survival, disease-free survival, and recurrence in non-small cell lung cancer patients.

Woods Nicholas T NT Monteiro Alvaro N AN Thompson Zachary J ZJ Amankwah Ernest K EK Naas Nina N Haura Eric B EB Beg Amer A AA Schabath Matthew B MB

Molecular carcinogenesis 20150118

Biomarkers based on germline DNA variations could have translational implications by identifying prognostic factors and sub-classifying patients to tailored, patient-specific treatment. To investigate the association between germline variations in interleukin (IL) genes and lung cancer outcomes, we genotyped 251 single nucleotide polymorphisms (SNPs) from 33 different IL genes in 651 non-small cell lung cancer (NSCLC) patients. Analyses were performed to investigate overall survival, disease-fre ...[more]

PMID: 25597281

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Project description:PurposeTo test, in a single-arm, prospective, phase 2 trial, whether adding the epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor erlotinib to concurrent chemoradiotherapy for previously untreated, locally advanced, inoperable non-small cell lung cancer would improve survival and disease control without increasing toxicity.Methods and materialsForty-eight patients with previously untreated non-small cell lung cancer received intensity modulated radiation therapy (63 Gy/35 fractions) on Monday through Friday, with chemotherapy (paclitaxel 45 mg/m², carboplatin area under the curve [AUC] = 2) on Mondays, for 7 weeks. All patients also received the EGFR tyrosine kinase inhibitor erlotinib (150 mg orally 1/d) on Tuesday-Sunday for 7 weeks, followed by consolidation paclitaxel-carboplatin. The primary endpoint was time to progression; secondary endpoints were overall survival (OS), toxicity, response, and disease control and whether any endpoint differed by EGFR mutation status.ResultsOf 46 patients evaluable for response, 40 were former or never-smokers, and 41 were evaluable for EGFR mutations (37 wild-type [WT] and 4 mutated [all adenocarcinoma]). Median time to progression was 14.0 months and did not differ by EGFR status. Toxicity was acceptable (no grade 5, 1 grade 4, 11 grade 3). Twelve patients (26%) had complete responses (10 WT, 2 mutated), 27 (59%) partial (21 WT, 2 mutated, 4 unknown), and 7 (15%) none (6 WT, 2 mutated, 1 unknown) (P=.610). At 37.0 months' follow-up (range, 3.6-76.5 months) for all patients, median OS time was 36.5 months, and 1-, 2-, and 5-year OS rates were 82.6%, 67.4%, and 35.9%, respectively; none differed by mutation status. Twelve patients had no progression, and 34 had local and/or distant failure. Eleven of 27 distant failures were in the brain (7 WT, 3 mutated, 1 unknown).ConclusionsToxicity and OS were promising, but time to progression did not meet expectations. The prevalence of distant failures underscores the need for effective systemic therapy.

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Interleukin polymorphisms associated with overall survival, disease-free survival, and recurrence in non-small cell lung cancer patients.

Publications

Interleukin polymorphisms associated with overall survival, disease-free survival, and recurrence in non-small cell lung cancer patients.

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