Abstract
e14034 Background: The Wnt/β-catenin signaling plays a central role in the development and progression of most colon cancers. Germline variants in Wnt/β-catenin pathway genes may result in altered gene function and/or activity, thereby causing inter-individual differences in relation to tumor recurrence capacity and chemoresistance. We investigated germline polymorphisms in a comprehensive panel of Wnt/β-catenin pathway genes to predict time to tumor recurrence (TTR) in patients with stage III and high-risk stage II colon cancer. Methods: A total of 234 patients treated with 5-fluorouracil-based chemotherapy at the University of Southern California were included in this study. Whole blood samples were analyzed for putative functional germline polymorphisms in SFRP3, SFRP4, DKK2, DKK3, Axin2, APC, TCF7L2, WNT5B, CXXC4 genes by PCR-RFLP or direct DNA-sequencing. We also included NOTCH2 and GLI1 variants which belong to the Notch and Hedgehog pathways respectively. Results: The minor allele of WNT5B rs2010851 T>G was significantly associated with a shorter TTR (4.9vs10.7 years; HR: 2.48; 95%CI, (0.96, 6.38); p=0.044) in high-risk stage II colon cancer patients. This result remained significant in the multivariate Cox regression analysis. Conclusions: Despite the importance of Wnt/β-catenin pathway in the development of cancer, only the WNT5B germline variant rs2010851 was significantly identified as a stage-dependent prognostic marker for colon cancer patients after 5-fluorouracil-based adjuvant therapy.
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