Discovering novel SNPs that are correlated with patient outcome in a Singaporean cancer patient cohort treated with gemcitabine-based chemotherapy

BMC Cancer
Vachiranee LimviphuvadhWei Peng Yong

Abstract

Single Nucleotide Polymorphisms (SNPs) can influence patient outcome such as drug response and toxicity after drug intervention. The purpose of this study is to develop a systematic pathway approach to accurately and efficiently predict novel non-synonymous SNPs (nsSNPs) that could be causative to gemcitabine-based chemotherapy treatment outcome in Singaporean non-small cell lung cancer (NSCLC) patients. Using a pathway approach that incorporates comprehensive protein-protein interaction data to systematically extend the gemcitabine pharmacologic pathway, we identified 77 related nsSNPs, common in the Singaporean population. After that, we used five computational criteria to prioritize the SNPs based on their importance for protein function. We specifically selected and screened six candidate SNPs in a patient cohort with NSCLC treated with gemcitabine-based chemotherapy. We performed survival analysis followed by hematologic toxicity analyses and found that three of six candidate SNPs are significantly correlated with the patient outcome (P < 0.05) i.e. ABCG2 Q141K (rs2231142), SLC29A3 S158F (rs780668) and POLR2A N764K (rs2228130). Our computational SNP candidate enrichment workflow approach was able to identify several high c...Continue Reading

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Citations

May 18, 2019·Expert Opinion on Drug Metabolism & Toxicology·Btissame El HassouniElisa Giovannetti
Feb 23, 2021·Molecular Biology Reports·Pérez-De Marcos Juan-CarlosTorres-Espíndola Luz-María
Sep 30, 2021·Cellular and Molecular Life Sciences : CMLS·Samiksha KukalRitushree Kukreti
Nov 17, 2021·Pharmacogenomics·Parul SharmaSiddharth Sharma

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Methods Mentioned

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