Interleukin polymorphisms associated with overall survival, disease‐free survival, and recurrence in non‐small cell lung cancer patients. Issue 1 (18th January 2015)

• Record Type: Journal Article
• Authors: Woods, Nicholas T.; Monteiro, Alvaro N.; Thompson, Zachary J.; Amankwah, Ernest K.; Naas, Nina; Haura, Eric B.; Beg, Amer A.; Schabath, Matthew B.; Schabath, Matthew B.; DiGiovanni, John
• Is Part Of: Molecular carcinogenesis. Volume 54:Issue 1(2015:Jan.)
• Page Start: E172
• Page End: E184
• Publication Date: 2015-01-18
• Subjects: Carcinogenesis -- Molecular aspects -- Periodicals; 616.994071
• DOI: 10.1002/mc.22275
• Languages: English
• ISSNs: 0899-1987

Abstract

<abstract abstract-type="main" xml:lang="en"> <title> <x xml:space="preserve">Abstract</x> </title> <sec id="mc22275-sec-0001" sec-type="section"> <p>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 <italic>interleukin</italic> (<italic>IL</italic>) genes and lung cancer outcomes, we genotyped 251 single nucleotide polymorphisms (SNPs) from 33 different <italic>IL</italic> 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 <italic>IL</italic> SNPs significantly associated with one or more of the lung cancer outcomes of interest. The GG genotype of <italic>IL16:rs7170924</italic> 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 (<italic>IL1A:rs1800587</italic>, <italic>IL1B:rs1143634</italic>, <italic>IL8:s12506479</italic>, <italic>IL12A:rs662959</italic>, and <italic>IL13:rs1881457</italic>) and <italic>IL16</italic>:<italic>rs7170924</italic> 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 (<italic>IL13:rs1881457</italic>, <italic>IL1B:rs1143634</italic>, <italic>and IL12A:rs662959</italic>), and for disease‐free survival, based on two SNPs (IL12A:rs662959 and IL16:rs7170924), which may suggest that these candidate <italic>IL</italic> SNPs have a specific impact on lung cancer progression and recurrence. These data suggest that germline variations in <italic>IL</italic> genes are associated with clinical outcomes in NSCLC patients. © 2015 Wiley Periodicals, Inc.</p> </sec> </abstract>