PMID: 22868256

Cecchin E, D'Andrea M, Lonardi S, Zanusso C, Pella N, Errante D, De Mattia E, Polesel J, Innocenti F, Toffoli G
A prospective validation pharmacogenomic study in the adjuvant setting of colorectal cancer patients treated with the 5-fluorouracil/leucovorin/oxaliplatin (FOLFOX4) regimen.
Pharmacogenomics J. 2012 Aug 7. doi: 10.1038/tpj.2012.31., [PubMed]
Sentences
No. Mutations Sentence Comment
123 ABCC2 p.Val417Ile
X
ABCC2 p.Val417Ile 22868256:123:119
status: NEW
view ABCC2 p.Val417Ile details
 Although this association did not pass the FDR cutoff (q-value 0.1109), rs2273697 is a missense polymorphism causing a Val417Ile amino-acid substitution increasing the transporter efficiency.41 Enhanced ABCC2 expression can lead to decreased cellular glutathione content.43 Glutathione is needed for oxaliplatin detoxification via conjugation, and it was reported that low glutathione intra-cellular levels can cause increased oxaliplatin cytotoxicity.40 Moreover, ABCC2 mediates the export of the oxaliplatin-glutathione conjugated form, and ABCC2 overexpressing cells were resistant to platinum derivatives.44 Taken together with our results, ABCC2 variants might change the susceptibility of patients to oxaliplatin toxicity via a glutathione-mediated mechanism. Login to comment