Genetic polymorphisms associated with outcome in multiple myeloma patients receiving high-dose melphalan.
High-dose melphalan (HDM) is an essential component in the treatment of patients with multiple myeloma (MM). Few data are available regarding genetic polymorphisms associated with patient outcome or toxicity in this setting. To identify such polymorphisms, we performed a retrospective analysis, genotyping single nucleotide polymorphisms (SNPs) with the arrayed primer extension (APEX) technology in 169 patients having received HDM for MM. We analyzed 209 SNPs in 95 genes involved in drug metabolism, DNA repair, cell cycle and apoptosis. SNPs in ABCB1, CYP3A4 and TP53BP2 were associated with response to VAD induction therapy (P<0.01). SNPs in ALDH2, GSTT2 and BRCA1 were associated with response to HDM (P<0.01). Polymorphisms in CYP1A1, RAD51 and PARP were associated with disease progression whereas polymorphisms in ALDH2 and CYP1A1 were correlated with OS. Polymorphisms in BRCA1, CDKN1A and XRCC1 were associated with the occurrence of severe mucositis after HDM. These results suggest that SNPs of genes involved in drug metabolism or DNA repair could be used to distinguish MM patient subgroups with different toxicity/efficacy profiles.
Dumontet
C
C
LCMT, Hospices Civils de Lyon, Lyon, France. charles.dumontet@chu-lyon.fr
Landi
S
S
Reiman
T
T
Perry
T
T
Plesa
A
A
Bellini
I
I
Barale
R
R
Pilarski
L M
LM
Troncy
J
J
Tavtigian
S
S
Gemignani
F
F
D000328:Adult; D000368:Aged; D004260:DNA Repair / Q000235:genetics; D005260:Female; D005838:Genotype; D006801:Humans; D008297:Male; D008558:Melphalan / Q000008:administration & dosage*; D008875:Middle Aged; D009101:Multiple Myeloma / Q000188:drug therapy* / Q000235:genetics*; D004364:Pharmaceutical Preparations / Q000378:metabolism; D010597:Pharmacogenetics / Q000379:methods; D011110:Polymorphism, Genetic; D020641:Polymorphism, Single Nucleotide; D012189:Retrospective Studies; D016896:Treatment Outcome
D004364:Pharmaceutical Preparations; D008558:Melphalan