Regulatory polymorphisms in β-tubulin IIa are associated with paclitaxel-induced peripheral neuropathy.

ABSTRACT:

Purpose

Peripheral neuropathy is the dose-limiting toxicity of paclitaxel, a chemotherapeutic drug widely used to treat several solid tumors such as breast, lung, and ovary. The cytotoxic effect of paclitaxel is mediated through β-tubulin binding in the cellular microtubules. In this study, we investigated the association between paclitaxel neurotoxicity risk and regulatory genetic variants in β-tubulin genes.

Experimental design

We measured variation in gene expression of three β-tubulin isotypes (I, IVb, and IIa) in lymphocytes from 100 healthy volunteers, sequenced the promoter region to identify polymorphisms putatively influencing gene expression and assessed the transcription rate of the identified variants using luciferase assays. To determine whether the identified r

SUBMITTER: Leandro-Garcia LJ 

PROVIDER: S-EPMC3664665 | biostudies-literature | 2012 Aug

REPOSITORIES: biostudies-literature