1. Potentially Functional SNPs (pfSNPs) as Novel Genomic Predictors of 5-FU Response in Metastatic Colorectal Cancer Patients.
- Author
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Wang, Jingbo, Wang, Xu, Zhao, Mingjue, Choo, Su Pin, Ong, Sin Jen, Ong, Simon Y. K., Chong, Samuel S., Teo, Yik Ying, and Lee, Caroline G. L.
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COLON cancer patients , *GENETICS of colon cancer , *SINGLE nucleotide polymorphisms , *BIOMARKERS , *MULTIVARIATE analysis , *PREDICTION theory - Abstract
5-Fluorouracil (5-FU) and its pro-drug Capecitabine have been widely used in treating colorectal cancer. However, not all patients will respond to the drug, hence there is a need to develop reliable early predictive biomarkers for 5-FU response. Here, we report a novel potentially functional Single Nucleotide Polymorphism (pfSNP) approach to identify SNPs that may serve as predictive biomarkers of response to 5-FU in Chinese metastatic colorectal cancer (CRC) patients. 1547 pfSNPs and one variable number tandem repeat (VNTR) in 139 genes in 5-FU drug (both PK and PD pathway) and colorectal cancer disease pathways were examined in 2 groups of CRC patients. Shrinkage of liver metastasis measured by RECIST criteria was used as the clinical end point. Four non-responder-specific pfSNPs were found to account for 37.5% of all non-responders (P<0.0003). Five additional pfSNPs were identified from a multivariate model (AUC under ROC = 0.875) that was applied for all other pfSNPs, excluding the non-responder-specific pfSNPs. These pfSNPs, which can differentiate the other non-responders from responders, mainly reside in tumor suppressor genes or genes implicated in colorectal cancer risk. Hence, a total of 9 novel SNPs with potential functional significance may be able to distinguish non-responders from responders to 5-FU. These pfSNPs may be useful biomarkers for predicting response to 5-FU. [ABSTRACT FROM AUTHOR]
- Published
- 2014
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