Abstract 4674: Associations between epidermal growth factor receptor polymorphism and survival in colorectal cancer patients treated with 5-FU based adjuvant chemotherapy

Abstract

Abstract Introduction: Colorectal cancer (CRC) is the second most common cancer and the third leading cause of cancer deaths in Taiwan. 5-Fluorouracil (5-FU) is one of the first line anti-cancer drugs used in the chemotherapy for CRC in older to raise survival rate. Epidermal growth factor receptor (EGFR) plays an important role to regulate gene expression causing cellular proliferation and apoptosis may induce malignant tumors. This retrospective study examined the association between EGFR polymorphism and overall survival of CRC patients treated with 5-FU-based chemotherapy. Methods: A total of 499 patients diagnosed with CRC and received 5-FU-based chemotherapy after surgery between 1995 January and 2001 December was included in the present study. We genotyped the EGFR R497K (Arg 497 Lys) polymorphism using the polymerase chain reaction combined with the restriction fragment length polymorphism analysis (PCR-RFLP). Survival analyses on EGFR polymorphism were displayed with Kaplan-Meier curves and performed with log-rank test. The association between EGFR genotypes and survival was analyzed using Cox proportional hazard models. Result: After 13 years follow-up, the median survival year was 4.56. The distribution of EGFR genotype was not significantly different by patients’ clinicopathologic characteristics. No significant EGFR genetic effects on overall survival were found in the present study, even the adjustment for age, gender, or tumor stage in the Cox proportional hazard models. However, in stage IV CRC patients, compared to the EGFR Arg/Arg genotype, the EGFR Arg/Lys and Lys/Lys genotypes were related to better overall survival with hazard ratio (HR) of 0.75 (95% CI = 0.49 – 1.15) and 0.61 (95% CI = 0.38 – 0.98), respectively. The Kaplan-Meier curves also showed that stage IV CRC patients carrying the EGFR Lys allele had a better survival (log-rank p = 0.07). Conclusion: Our findings suggest that the EGFR R497K polymorphism may modify drugs activity to serve a prognostic predictor for stage IV CRC patients who receive 5-FU-based chemotherapy. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 4674. doi:10.1158/1538-7445.AM2011-4674