PMID- 24351404
OWN - NLM
STAT- MEDLINE
DCOM- 20150330
LR  - 20200206
IS  - 1569-8041 (Electronic)
IS  - 0923-7534 (Linking)
VI  - 25
IP  - 2
DP  - 2014 Feb
TI  - Pharmacogenetic predictors of severe peripheral neuropathy in colon cancer 
      patients treated with oxaliplatin-based adjuvant chemotherapy: a GEMCAD group 
      study.
PG  - 398-403
LID - 10.1093/annonc/mdt546 [doi]
AB  - BACKGROUND: Oxaliplatin-based chemotherapy (CT), widely used as adjuvant therapy 
      for stage III and selected high-risk stage II colon cancer (CC) patients, is 
      often associated with cumulative peripheral neuropathy. Our aim is to identify 
      single-nucleotide polymorphisms (SNPs) in genes involved in oxaliplatin 
      metabolism, DNA repair mechanisms, cell cycle control, detoxification or 
      excretion pathways to predict severe (grade 2-3) oxaliplatin-induced peripheral 
      neuropathy (OXPN) among CC patients treated with oxaliplatin and 
      fluoropyrimidine-based adjuvant CT. PATIENTS AND METHODS: Genomic DNA was 
      extracted from formalin-fixed-paraffin-embedded peritumoral samples from 206 
      high-risk stage II and stage III CC patients receiving oxaliplatin-based adjuvant 
      CT from January 2004 to December 2009. Genotyping was carried out for 34 SNPs in 
      15 genes using MassARRAY (SEQUENOM) technology. A total of 181 stage II-III CC 
      patients treated with the same CT regimens were enrolled as a validation set. 
      RESULTS: The rs2230641 cyclin H (CCNH) rs2230641 C/C [odd ratio (OR)=5.03, 95% 
      confidence interval (CI) 1.061-2.41, P=0.042] and the ATP-binding cassette 
      subfamily G, member 2 (ABCG2) rs3114018 A/A genotypes (OR=2.67; 95% CI 0.95-4.41; 
      P=0.059) were associated with a higher risk of severe OXPN. In addition, patients 
      harboring the combination of CCNH C/C and/or the ABCG2 rs3114018 A/A genotypes 
      had a higher risk of grade 2-3 OXPN than those with the CCNH any T and ABCG2 any 
      C genotypes (37.73% versus 19.42%; OR=2.46; 95% CI 1.19-5.07; P=0.014) in the 
      logistic regression analysis using age, gender, adjuvant CT regimen and 
      cumulative dose of oxaliplatin as covariates. The ability to predict severe OXPN 
      of this combined analysis was independently validated in the second cohort (58% 
      versus 33.33%; OR=2.99; 95% CI 1.45-6.13; P=0.002). CONCLUSIONS: Our results 
      suggest that SNPs in CCNH and ABCG2 can modulate the development of severe OXPN 
      among stage II-III CC patients who received oxaliplatin-based CT, thus enabling 
      the individualization of adjuvant treatment.
FAU - Custodio, A
AU  - Custodio A
AD  - Department of Medical Oncology, La Paz Universitary Hospital, IdiPaz, Madrid.
FAU - Moreno-Rubio, J
AU  - Moreno-Rubio J
FAU - Aparicio, J
AU  - Aparicio J
FAU - Gallego-Plazas, J
AU  - Gallego-Plazas J
FAU - Yaya, R
AU  - Yaya R
FAU - Maurel, J
AU  - Maurel J
FAU - Higuera, O
AU  - Higuera O
FAU - Burgos, E
AU  - Burgos E
FAU - Ramos, D
AU  - Ramos D
FAU - Calatrava, A
AU  - Calatrava A
FAU - Andrada, E
AU  - Andrada E
FAU - Lopez, R
AU  - Lopez R
FAU - Moreno, V
AU  - Moreno V
FAU - Madero, R
AU  - Madero R
FAU - Cejas, P
AU  - Cejas P
FAU - Feliu, J
AU  - Feliu J
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20131218
PL  - England
TA  - Ann Oncol
JT  - Annals of oncology : official journal of the European Society for Medical 
      Oncology
JID - 9007735
RN  - 0 (ABCG2 protein, human)
RN  - 0 (ATP Binding Cassette Transporter, Subfamily G, Member 2)
RN  - 0 (ATP-Binding Cassette Transporters)
RN  - 0 (CCNH protein, human)
RN  - 0 (Cyclin H)
RN  - 0 (Neoplasm Proteins)
RN  - 0 (Organoplatinum Compounds)
RN  - 04ZR38536J (Oxaliplatin)
SB  - IM
MH  - ATP Binding Cassette Transporter, Subfamily G, Member 2
MH  - ATP-Binding Cassette Transporters/*genetics
MH  - Adult
MH  - Aged
MH  - Aged, 80 and over
MH  - Antineoplastic Combined Chemotherapy Protocols/*adverse effects/therapeutic use
MH  - Chemotherapy, Adjuvant
MH  - Colonic Neoplasms/*drug therapy/genetics/mortality
MH  - Cyclin H/*genetics
MH  - Female
MH  - Genetic Association Studies
MH  - Humans
MH  - Male
MH  - Middle Aged
MH  - Neoplasm Proteins/*genetics
MH  - Organoplatinum Compounds/administration & dosage
MH  - Oxaliplatin
MH  - Peripheral Nervous System Diseases/chemically induced/*genetics
MH  - *Polymorphism, Single Nucleotide
MH  - Retrospective Studies
MH  - Young Adult
OTO - NOTNLM
OT  - adjuvant chemotherapy
OT  - colon cancer
OT  - early-stage
OT  - oxaliplatin
OT  - peripheral neuropathy
OT  - single-nucleotide polymorphism
EDAT- 2013/12/20 06:00
MHDA- 2015/03/31 06:00
CRDT- 2013/12/20 06:00
PHST- 2013/12/20 06:00 [entrez]
PHST- 2013/12/20 06:00 [pubmed]
PHST- 2015/03/31 06:00 [medline]
AID - S0923-7534(19)36462-2 [pii]
AID - 10.1093/annonc/mdt546 [doi]
PST - ppublish
SO  - Ann Oncol. 2014 Feb;25(2):398-403. doi: 10.1093/annonc/mdt546. Epub 2013 Dec 18.