Background Inter-individual differences in drug efficacy and toxicity are linked, in many cases, to single nucleotide polymorphisms (SNPs) in genes coding for drug metabolising enzymes and transporters. Taxanes are active for several tumour types, including breast cancer. But this is limited by adverse events such as neurotoxicity and haematological toxicity.
Purpose To evaluate the associations between a panel of 92 SNPs in 33 genes and adverse events developed by breast cancer patients treated with taxanes.
Materials and Methods Between June 2011 and May 2012 breast cancer patients treated with taxanes who gave informed consent were genotyped for 92 SNPs in 33 genes. Genomic DNA was analysed by a genetic analysis platform (MassArray, Sequenom). Hardy-Weinberg equilibrium was assessed. Clinical data were recorded. The association between genotypes and adverse reactions was assessed with Fisher’s exact test and X2-test.
Results Sixty-seven Caucasian women (mean age: 53 years old; 95%CI = 49–56) were genotyped. All genotype frequencies were in Hardy-Weinberg equilibrium. 53.7% (n = 36) of the patients were treated with docetaxel and 46.3% (n = 31) with paclitaxel. Histotypes: 88.1% (n = 59) ductal, 7.5% (n = 5) lobular and 4.5% (n = 3) other. Significant associations were found between: A) Overall grade III–IV toxicity: TP53 rs1045522 [10.8% (n = 4) GG vs. 43.3% (n = 13) GC/CC, p = 0.004]; DNA repair gene XPC rs2228001 [8.7% (n = 2) AA vs. 34.1% (n = 15) AC/CC, p = 0.037]. B) Anaemia grade II–IV: ERCC2 rs1799793 [7.1% (n = 2) GG vs. 33.3% (n = 13) GA/AA, p = 0.016]; XPC rs2228001 [4.3% (n = 1) AA vs. 31.8% (n = 14) AC/CC, p = 0.012]. C) Neutropenia grade II–IV: CYP2C8 rs1341164 [6.5% (n = 2) TT vs. 27.8% (n = 10) TC/CC, p = 0.028]; TP53 rs1045522 [8.1% (n = 3) GG vs. 30.0% (n = 9) GC/CC, p = 0.027]; XPC rs2228001 [0.0% AA vs. 27.3% (n = 12) AC/CC, p = 0.006]. D) Diarrhoea grade II–IV: ABCB1 rs1128503 [21.4% (n = 6) TT vs. 2.6% (n = 1) TC/CC, p = 0.018]; CYP1B1 rs72549389 [20.0% (n = 7) TT vs. 0% TG/GG, p = 0.014]. No associations with neurotoxicity were found.
Conclusions Studying genetic variations can help to identify patients at higher risk of suffering adverse events and provides useful information to individualise therapy.
No conflict of interest.
Statistics from Altmetric.com
If you wish to reuse any or all of this article please use the link below which will take you to the Copyright Clearance Center’s RightsLink service. You will be able to get a quick price and instant permission to reuse the content in many different ways.