Genetic variants in RPA1 associated with the response to oxaliplatin-based chemotherapy in colorectal cancer.
Alleles
Antineoplastic Combined Chemotherapy Protocols
/ pharmacology
Apoptosis
/ genetics
Cell Line, Tumor
Cell Proliferation
/ genetics
Colorectal Neoplasms
/ drug therapy
DNA Repair
/ genetics
Gene Knockdown Techniques
Genetic Variation
Genotype
Humans
Oxaliplatin
/ pharmacology
Polymorphism, Single Nucleotide
Progression-Free Survival
Replication Protein A
/ genetics
Colorectal cancer
Genetic variants
Nucleotide excision repair
Oxaliplatin
Survival
Journal
Journal of gastroenterology
ISSN: 1435-5922
Titre abrégé: J Gastroenterol
Pays: Japan
ID NLM: 9430794
Informations de publication
Date de publication:
Nov 2019
Nov 2019
Historique:
received:
19
08
2018
accepted:
12
03
2019
pubmed:
30
3
2019
medline:
15
8
2020
entrez:
30
3
2019
Statut:
ppublish
Résumé
Oxaliplatin (L-OHP) is a commonly used first-line chemotherapy for colorectal cancer. Genetic variants in nucleotide excision repair (NER) pathway genes may alter genomic integrity and the efficacy of oxaliplatin-based chemotherapy in colorectal cancer. We investigated the association between genetic variants in 19 NER pathway genes and the disease control rate (DCR) and progression-free survival (PFS) among 166 colorectal cancer patients who received oxaliplatin-based chemotherapy. Expression quantitative trait loci (eQTL) analysis was performed using the Genotype-Tissue Expression (GTEx) portal. Gene harboring significant SNP was overexpressed or knocked down to demonstrate the effect on cell phenotypes with or without oxaliplatin treatment. We found that rs5030740, located in the 3'-untranslated region (3'-UTR) of RPA1, was associated with DCR [OR = 2.99 (1.33-5.69), P = 4.00 × 10 Our findings demonstrate an association between rs5030740 and the DCR and PFS of colorectal cancer patients. RPA1 functions as a putative oncogene in tumorigenesis by reducing sensitivity to oxaliplatin and could serve as a potential prognostic biomarker in colorectal cancer.
Sections du résumé
BACKGROUND
BACKGROUND
Oxaliplatin (L-OHP) is a commonly used first-line chemotherapy for colorectal cancer. Genetic variants in nucleotide excision repair (NER) pathway genes may alter genomic integrity and the efficacy of oxaliplatin-based chemotherapy in colorectal cancer.
METHODS
METHODS
We investigated the association between genetic variants in 19 NER pathway genes and the disease control rate (DCR) and progression-free survival (PFS) among 166 colorectal cancer patients who received oxaliplatin-based chemotherapy. Expression quantitative trait loci (eQTL) analysis was performed using the Genotype-Tissue Expression (GTEx) portal. Gene harboring significant SNP was overexpressed or knocked down to demonstrate the effect on cell phenotypes with or without oxaliplatin treatment.
RESULTS
RESULTS
We found that rs5030740, located in the 3'-untranslated region (3'-UTR) of RPA1, was associated with DCR [OR = 2.99 (1.33-5.69), P = 4.00 × 10
CONCLUSIONS
CONCLUSIONS
Our findings demonstrate an association between rs5030740 and the DCR and PFS of colorectal cancer patients. RPA1 functions as a putative oncogene in tumorigenesis by reducing sensitivity to oxaliplatin and could serve as a potential prognostic biomarker in colorectal cancer.
Identifiants
pubmed: 30923916
doi: 10.1007/s00535-019-01571-z
pii: 10.1007/s00535-019-01571-z
doi:
Substances chimiques
RPA1 protein, human
0
Replication Protein A
0
Oxaliplatin
04ZR38536J
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
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