Predictive value of ERCC2, ABCC2 and MMP2 of response and long-term survival in locally advanced head and neck cancer patients treated with chemoradiotherapy.
Adult
Aged
Aged, 80 and over
Chemoradiotherapy
Female
Gene Frequency
Haplotypes
Head and Neck Neoplasms
/ genetics
Humans
Male
Matrix Metalloproteinase 2
/ genetics
Middle Aged
Multidrug Resistance-Associated Protein 2
/ genetics
Pharmacogenomic Variants
Polymorphism, Single Nucleotide
Treatment Outcome
Xeroderma Pigmentosum Group D Protein
/ genetics
ABCC2
Chemoradiotherapy
ERCC2
Head and neck
MMP2
Outcomes
Survival
Journal
Cancer chemotherapy and pharmacology
ISSN: 1432-0843
Titre abrégé: Cancer Chemother Pharmacol
Pays: Germany
ID NLM: 7806519
Informations de publication
Date de publication:
11 2021
11 2021
Historique:
received:
18
03
2021
accepted:
10
07
2021
pubmed:
27
7
2021
medline:
4
1
2022
entrez:
26
7
2021
Statut:
ppublish
Résumé
Genetic variants in genes involved in the distribution, metabolism, accumulation or repair of lesions are likely to influence the response of drugs used in the treatment of Head and Neck Cancer (HNC). We examine the effect of 36 SNPs on clinical outcomes in patients with locally advanced HNC who were receiving platinum-based chemoradiotherapy (CRT). These SNPs were genotyped in 110 patients using the iPLEX Gold assay on the MassARRAY method in blood DNA samples and used Kaplan-Meier and Cox regression analyses to compare genotype groups with the survival. Two SNPs, rs717620 (ABCC2) and rs12934241 (MMP2) were strongly associated with overall survival (OS) and disease-free survival (DFS). At a median follow-up of 64.4 months, the allele A of rs717620 (ABCC2) had an increased risk of disease progression {hazard ratio [HR] = 1.79, p = 0.0018} and death (HR = 2.0, p = 0.00027). ABCC2 was associated with OS after a Bonferroni adjustment for multiple testing. The MMP2 rs12934241-T allele was associated with an increased risk of worse OS and DFS (p = 0.0098 and p = 0.0015, respectively). One SNP of ABCB1 and three SNPs located in the ERCC2 gene showed an association with response in the subgroup of HNC patients treated with definitive CRT. Our findings highlight the potential usefulness of SNPs in different genes involved in drug metabolism and repair DNA to predict the response and survival to CRT. ABCC2 is a potential predictor of OS in patients with HNC.
Identifiants
pubmed: 34309735
doi: 10.1007/s00280-021-04330-1
pii: 10.1007/s00280-021-04330-1
doi:
Substances chimiques
ABCC2 protein, human
0
Multidrug Resistance-Associated Protein 2
0
MMP2 protein, human
EC 3.4.24.24
Matrix Metalloproteinase 2
EC 3.4.24.24
Xeroderma Pigmentosum Group D Protein
EC 3.6.4.12
ERCC2 protein, human
EC 5.99.-
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
813-823Informations de copyright
© 2021. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.
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