Oxaliplatin-based chemotherapy exerts its effects through generating DNA damage. Hence, genetic variants in DNA repair pathways could modulate treatment response. We used a prospective cohort of 623 colorectal cancer patients with stage II-IV disease treated with adjuvant/palliative chemotherapy to comprehensively investigate 1727 genetic variants in the DNA repair pathways as potential predictive markers for oxaliplatin treatment. Single nucleotide polymorphisms (SNP) associations with overall survival and recurrence-free survival were assessed using a Cox regression model. Pathway analysis was performed using the gamma method. Patients carrying variant alleles of rs3783819 (MNAT1) and rs1043953 (XPC) experienced a longer overall survival after treatment with oxaliplatin than patients who did not carry the variant allele, while the opposite association was found in patients who were not treated with oxaliplatin (false discovery rate-adjusted P-values for heterogeneity 0.0047 and 0.0237, respectively). The nucleotide excision repair (NER) pathway was found to be most likely associated with overall survival in patients who received oxaliplatin (P-value=0.002). Our data show that genetic variants in the NER pathway are potentially predictive of treatment response to oxaliplatin.The Pharmacogenomics Journal advance online publication, 17 March 2015; doi:10.1038/tpj.2015.8.
Pharmacology, Toxicology and Pharmaceutical Science
2
6%
Biochemistry, Genetics and Molecular Biology
2
6%
Nursing and Health Professions
2
6%
Agricultural and Biological Sciences
2
6%
Other
1
3%
Unknown
13
41%
Attention Score in Context
Attention Score in Context
This research output has an Altmetric Attention Score of 1. This is our high-level measure of the quality and quantity of online attention that it has received. This Attention Score, as well as the ranking and number of research outputs shown below, was calculated when the research output was last mentioned on 07 September 2016.
All research outputs
#21,500,020
of 24,003,070 outputs
Outputs from The Pharmacogenomics Journal
#821
of 854 outputs
Outputs of similar age
#248,752
of 289,984 outputs
Outputs of similar age from The Pharmacogenomics Journal
#21
of 23 outputs
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