LMTK3 polymorphism in patients with metastatic colon cancer.

Abstract

471 Background: LMTKs are a family of serine-threonine-tyrosine kinases. LMTK3 isoform is a potent regulator of estrogen receptor activity LMTK3 gene polymorphisms affect DFS and OS of breast cancer patients. Cumulative evidence implies that estrogen receptor signalling plays a role in colon carcinoma development and progression. We investigated whether the LMTK3 rs9989661 SNP is a prognostic factor in patients with advanced colon cancer. Methods: 318 patients with metastatic colon cancer treated at the USC/Norris Comprehensive Cancer Center or the LA County/USC Medical Center were included in this study. Genomic DNA was extracted from white blood cells of peripheral blood samples using the QiaAmp kit (Qiagen, Valencia, CA). The LMTK3 polymorphism was genotyped by PCR-RFLP. The association between the LMTK3 polymorphism and overall survival was examined using the log-rank test and multivariate Cox-model. Results: There were 141 females and 177 males, with a median age of 58 years (range 25-86). The cohort comprised 234 whites, 43 Asians, 15 Blacks, 24 Hispanics, and 2 Native Americans. The median survival was 13.7 months with a median follow-up of 2.3 years. The median overall survival was 16.6 vs. 12.8 months for patients with C/- vs. patients with T/T (HR=0.78; 95% CI: 0.56-1.08; p=0.055). At a multivariate analysis restricted to subjects with left-sided disease (n=126) the median OS for patients with C/- genotype was 23.8 months compared to 14.9 months of T/T patients (HR=0.51; 95%CI: 0.28-0.91; p=0.014). Conclusions: This study suggests that LMTK3 may be an independent prognostic factor for patients with metastatic colon cancer and raise the issue of possible disparities according to primary tumor location. Our group produced similar results also in the adjuvant setting. Functional correlative preclinical analyses and external clinical validation studies are currently ongoing.