Identification of polymorphisms associated with hypertriglyceridemia and prolonged survival induced by bexarotene in treating non-small cell lung cancer.

Background: Bexarotene was evaluated in treating advanced non small cell lung cancer (NSCLC) in two phase III trials. Although a significant survival benefit was not observed for the overall bexarotene-treated population (617 patients), a third of bexarotene-treated patients who developed high-grade hypertriglyceridemia exhibited significantly longer survival. Patients and Methods: In order to identify genomic polymorphisms that could serve as potential predictive biomarkers for response and improved survival in NSCLC patients, DNA samples extracted from plasma archived from 403 patients were genotyped using Affymetrix 500K whole genome SNP arrays and/or Sequenom iPLEX (TM) assays. Results: Fourteen SNPs were identified on nine loci that showed significant associations with high-grade hypertriglyceridemia induced by bexarotene. Four such single nucleotide polymorphisms (SNPs) reside on the region upstream of solute carrier family 10, member 2 (SLC10A2), and one SNP is located close to lymphocyte cytosolic protein 1 (LCP1), whose expression correlated with the activity of bexarotene in tumor cells. Conclusion: We identified novel polymorphisms exhibiting significant association with bexarotene induced hypertriglyceridemia, implicating their potential in predicting bexarotene-improved survival response.