Premium
Genetic associations of docetaxel‐based chemotherapy‐induced myelosuppression in Chinese Han population
Author(s) -
Ren Weihua,
Zhou Chenxi,
Liu Yedong,
Su Keli,
Jia Li,
Chen Luan,
Li Mo,
Ma Jingsong,
Zhou Wei,
Zhang Suli,
Zhang Di,
Cong Zhiliang,
Niu Xuecai,
Zhang Shengui,
Shen Lu,
Huai Cong,
Sun Xiaofang,
Li Guorong,
Qin Shengying,
Guo Liang
Publication year - 2020
Publication title -
journal of clinical pharmacy and therapeutics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.622
H-Index - 73
eISSN - 1365-2710
pISSN - 0269-4727
DOI - 10.1111/jcpt.13084
Subject(s) - docetaxel , medicine , multifactor dimensionality reduction , oncology , single nucleotide polymorphism , genotyping , pharmacology , chemotherapy , genotype , gene , genetics , biology
What is known and objective Myelosuppression, an adverse drug reaction (ADR), often causes medical treatment termination in cancer patients. It has been known that genetic components, such as single‐nucleotide polymorphisms (SNPs), influence the risk of myelosuppression at the individual‐patient level. However, due to ethnic variation in frequency of genetic polymorphisms, results reported in Caucasian patients may not be generalizable to the Chinese Han population. Until now, few researches on myelosuppression included Chinese Han patients. In this study, we conducted a systematic study of potential biomarkers for docetaxel‐induced myelosuppression in Han Chinese patients. Methods We examined 61 SNPs in 36 genes that code for drug transporters, metabolism enzymes, nuclear receptors and DNA repair pathway in 110 Chinese Han patients receiving docetaxel‐based chemotherapy. Genotyping was conducted using the Sequenom MassARRAY system. Significant SNPs were identified by logistic regression, and gene‐gene interactions were investigated by generalized multifactor dimensionality reduction (GMDR) analysis. Results and discussion Our results revealed that 11 SNPs in nine genes ( SLC15A1 , SLCO1A2 , CYP2D6 , FMO3 , UGT1A1 , NAT2 , SULT2A1 , PXR and HNF4α ) were associated with docetaxel‐induced myelosuppression. GMDR analyses suggested that a 3‐locus model: SLC15A1 rs2297322— PXR rs3732359— FMO3 rs2266782 was an appropriate predictive model of docetaxel‐induced myelosuppression ( P = .017, Testing Bal.Acc = 0.653, CV Consistency = 10/10). What is new and conclusion Our findings suggest multiple novel predictive biomarkers of docetaxel‐induced myelosuppression: SLC15A1 rs2297322, PXR rs3732359 and FMO3 rs2266782. These discoveries should help in advancing future personalized therapy of docetaxel‐based chemotherapy specific to Chinese Han patients.