TITLE:
The Predictive Value of Germline Polymorphisms in Patients with NSCLC
AUTHORS:
Anneli Nygaard, Karen-Lise Spindler, Christa Nyhus, Rikke Andersen, Anders Jakobsen
KEYWORDS:
NSCLC, EGF, VEGF, DNA excision repair, SNPs
JOURNAL NAME:
Journal of Cancer Therapy,
Vol.1 No.4,
December
31,
2010
ABSTRACT: Lung cancer is one of the most common cancers in the western world, and closely related to smoking. The majority of the patients can not be offered treatment with curative intent. Palliative chemotherapy has limited effect but a considerable level of toxicity. Predictive markers are therefore urgently needed. Single Nucleotide Polymorphisms (SNPs) are stable markers of potential clinical value and the study aimed at evaluating their use in lung cancer patients given standard chemotherapy. Genomic DNA was extracted from a pre-treatment blood sample drawn from patients with advanced Non-Small Celled Lung Cancer (NSCLC), referred to palliative chemotherapy (Carboplatin and Vinorelbine) at the Department of Oncology, Vejle Hospital, between 2007 and 2010. Eighty-seven patients were included in a test cohort, and 161 patients in an independent validation cohort. A panel of 107 SNPs in the EGF, VEGF and DNA-excision repair systems was investigated. The primary endpoint was response rates (RR). Secondary endpoints were progression free survival (PFS) and overall survival (OS). SNPs with significant association to outcome in the test cohort were further tested in the validation cohort. Haplotypes were estimated and analyzed when relevant. There were no significant associations between SNPs in the EGF system or the DNA-repair system and RR, PFS or OS. In contrast, the VEGF+405, VEGF-460 and VEGF-2579, heterozygous patients had a higher response rate and longer PFS than homozygous patients. Haplotype analysis of the VEGF+405 and VEGF-460 supported our findings. These results were, however, not confirmed in the validation cohort. Although significant results regarding VEGF related SNPs, in the primary analysis, no predictive value of a broad panel of SNPs in NSCLC was found in the validation cohort, underlining the importance of independent validation of biomarker analysis.