Cyclin D1 and epidermal growth factor polymorphisms associated with survival in patients with advanced colorectal cancer treated with Cetuximab

摘要: The study aimed to investigate whether polymorphisms in genes of the EGFR signaling pathway are associated with clinical outcome advanced colorectal cancer (CRC) patients treated single-agent Cetuximab. Polymorphisms interest include: cyclin D1 (CCND1) A870G, cyclooxygenase 2 (Cox-2) G-765C, epidermal growth factor (EGF) A61G, receptor (EGFR) codon R497 K, CA dinucleotide repeat intron 1, interleukin (IL)-8 T-251A and vascular endothelial (VEGF) C936 T gene polymorphisms. Thirty-nine metastatic CRC were enrolled IMCL-0144 trial Using polymerase chain reaction-restriction fragment length polymorphism method, CCND1, COX-2, EGF, EGFR, IL-8 VEGF assessed from genomic DNA extracted blood samples. A significant association was found between CCND1 A870G overall survival our 39 subjects. Patients AA homozygous genotype survived for a median 2.3 months [95% confidence interval (CI)=2.1-5.7], whereas those any G allele (AG, GG genotype) 8.7 (95% CI=4.4-13.5) (P=0.019, log-rank test). When we analysed EGF together, favourable genotypes (EGF allele) showed time 12 CI=4.8-15.2), two unfavourable or AA) 4.4 CI=2.1-5.7) (P=0.004, findings this pilot suggest that A61G may be useful molecular markers predicting