SNPs in transporter and metabolizing genes as predictive markers for oxaliplatin treatment in colorectal cancer patients

International Journal of Cancer. Journal International Du Cancer
Elisabeth J KapJenny Chang-Claude

Abstract

Oxaliplatin is frequently used as part of a chemotherapeutic regimen with 5-fluorouracil in the treatment of colorectal cancer (CRC). The cellular availability of oxaliplatin is dependent on metabolic and transporter enzymes. Variants in genes encoding these enzymes may cause variation in response to oxaliplatin and could be potential predictive markers. Therefore, we used a two-step procedure to comprehensively investigate 1,444 single nucleotide polymorphisms (SNPs) from these pathways for their potential as predictive markers for oxaliplatin treatment, using 623 stage II-IV CRC patients (of whom 201 patients received oxaliplatin) from a German prospective patient cohort treated with adjuvant or palliative chemotherapy. First, all genes were screened using the global test that evaluated SNP*oxaliplatin interaction terms per gene. Second, one model was created by backward elimination on all SNP*oxaliplatin interactions of the selected genes. The statistical procedure was evaluated using bootstrap analyses. Nine genes differentially associated with overall survival according to oxaliplatin treatment (unadjusted p values < 0.05) were selected. Model selection resulted in the inclusion of 14 SNPs from eight genes (six transporter...Continue Reading

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Mar 10, 2018·Anatomical Science International·Masanori TachikawaTetsuya Terasaki
Dec 6, 2017·Environmental and Molecular Mutagenesis·Bridgett KnoxSusan A Kadlubar
Mar 25, 2020·Human Genetics·Qingyang XiaoVolker M Lauschke
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Aug 14, 2021·Journal of Evidence-based Medicine·Jing-Quan WangZhe-Sheng Chen

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