Pharmacogenetic biomarkers for predisposition to toxicity to adjuvant FOLFOX/XELOX in colorectal cancer

التفاصيل البيبلوغرافية
العنوان: Pharmacogenetic biomarkers for predisposition to toxicity to adjuvant FOLFOX/XELOX in colorectal cancer
المؤلفون: María Sanjurjo-Sáez, Andrés Muñoz, Eva González-Haba, Lucia Cortejoso-Fernandez, Luis A. López-Fernández, Miguel Martín, Maria-Isabel Garcia-Garcia, Montse Blanco Codeisido, Pilar Alfonso, Daniel Lopez-Trabada Ataz
المصدر: Journal of Clinical Oncology. 31:390-390
بيانات النشر: American Society of Clinical Oncology (ASCO), 2013.
سنة النشر: 2013
مصطلحات موضوعية: Oncology, Cancer Research, medicine.medical_specialty, biology, business.industry, Colorectal cancer, medicine.disease, Oxaliplatin, Capecitabine, FOLFOX, Methylenetetrahydrofolate reductase, Internal medicine, biology.protein, Medicine, DPYD, ERCC1, business, Pharmacogenetics, medicine.drug
الوصف: 390 Background: 5-fluorouracil and capecitabine are the gold standards in colorectal cancer (CRC) treatment and are often combined with oxaliplatin (FOLFOX and XELOX chemotherapy, respectively). Our purpose was to analyze associations between severe adverse reactions to these regimes and polymorphisms in genes related to these drugs Methods: Retrospective study with 47 adult CRC patients treated with adjuvant FOLFOX/XELOX. 20 polymorphisms in 14 genes were selected: 6 genes [XRCC1 (rs25487), ERCC2 (rs131181), ERCC1 (rs11615), GSTP1 (rs1695), EGFR (rs4559542) and GSTT1 (copy number variation)] related to the pharmacokinetics and dynamics of oxaliplatin and 8 related to fluoropyrimidines [MTHFR (rs1801131 and rs1801133), DPYD (rs2297595 and rs3918290), TYMS (rs34743033 and rs34489327), ABCB1 (rs1128503, rs2032582 and rs1045642), ABCC4 (rs4148551 and rs3742106), ABCC5 (rs3805114), CYP2A6 (rs3742106 ) and CDA (rs2072671)]. Linear by linear association chi-square test (SPSS v.18.0.) was used to study associations. A multivariate analysis including sex and performance status was also conducted. p< 0.05 was considered significant. Results: Mean age was 62 (SD: 12) years and 78.7% male. Univariate analysis: statistically significant associations were obtained between rs11615 (ERCC1), neutropenia and hand-foot syndrome; rs3742106 (CYP2A6) and neutropenia; rs34743033 and rs34489327 (TYMS) and nausea/vomiting; and CNV of GSTT1 and neutropenia. Multivariate analysis: statistically significant associations were obtained between rs3742106 (CYP2A6) and neutropenia (GT vs. TT: OR, 0.042, 95% CI, 0004-0499, p = 0.012); rs2297595 (DPYD) and nausea/vomiting (GA vs AA: OR, 0.051, 95% CI, 0003-0772, p = 0.032); and rs11615 (ERCC1) and neutropenia (CC vs CT / TT: OR, 0.099, 95% CI, 0016-0615, p = 0.013) Conclusions: These results could help oncologists reduce adverse reactions associated to FOLFOX and XELOX chemotherapy by giving patients the best possible option, thus, improving their quality of life. Bigger cohorts are needed to verify the polymorphisms in ERCC1, CYP2A6, TYMS, DPYD and GSTT1 prior application in clinical practice.
تدمد: 1527-7755
0732-183X
DOI: 10.1200/jco.2013.31.4_suppl.390
URL الوصول: https://explore.openaire.eu/search/publication?articleId=doi_________::c1e7d05554d82d5e5603309907f4a584
https://doi.org/10.1200/jco.2013.31.4_suppl.390
رقم الانضمام: edsair.doi...........c1e7d05554d82d5e5603309907f4a584
قاعدة البيانات: OpenAIRE
الوصف
تدمد:15277755
0732183X
DOI:10.1200/jco.2013.31.4_suppl.390