ABCMdb

PMID: 22041137

Kiyotani K, Mushiroda T, Nakamura Y, Zembutsu H
Pharmacogenomics of tamoxifen: roles of drug metabolizing enzymes and transporters.
Drug Metab Pharmacokinet. 2012;27(1):122-31. Epub 2011 Nov 1., [PubMed]

Sentences

No. Mutations Sentence Comment

74 ABCC2 p.Val417Ile Recent SNP screening for the ABCC2 gene identified several common SNPs such as %1774delG ¤*1A¥, %24ChT ¤*1C¥ and 1249GhA ¤*2¥.80,81¥ No functional significance of 1249GhA causing Val417Ile has been shown in vitro,82,83¥ but its in vivo association was reported.84¥ %1774delG and %24ChT are associated with reduction of its promoter activity.82,85¥ In our recent study, an intronic SNP of ABCC2 ¤rs3740065¥ was found to be significantly associated with the clinical outcome of patients with tamoxifen therapy, whereas this SNP was not associated with plasma concentration of endoxifen or 4-hydroxytamoxifen, suggesting that the contribution of ABCC2 to biliary excretion of tamoxifen and its metabolites might be limited ¤Fig. 2¥.38¥ An in vitro study reporting that ABCC2 was expressed at higher levels in tamoxifen-resistant breast cancer cells suggests the possibility that active metabolites of tamoxifen are transported by ABCC2 from breast cancer cells.86¥ As described previously,87,88¥ rs3740065A/G is in strong linkage disequilibrium ¤r2 (c) 0.89¥ with %1774G/ delG, which was reported to be associated with decreased ABCC2 promoter activity. Login to comment