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open access
Published online 2016 Mar 23
Abstract
Background:
A gene signature associated with chemo-response in ovarian cancer was
created through integration of biological data in The Cancer Genome
Atlas (TCGA) and validated in five independent microarray experiments.
Our study aimed to determine if single nucleotide polymorphisms (SNPs)
within the 422-gene signature were associated with a genetic
predisposition to platinum-based chemotherapy response in serous ovarian
cancer.
Methods: An association analysis between SNPs within the
422-gene signature and chemo-response in serous ovarian cancer was
performed under the log-additive genetic model using the ‘SNPassoc’
package within the R environment (p<0.0001). Subsequent validation of
statistically significant SNPs was done in the Ovarian Cancer
Association Consortium (OCAC) database.
Results: 19 SNPs were found to
be associated with chemo-response with statistical significance. None of
the SNPs found significant in TCGA were validated within OCAC for the
outcome of interest, chemo-response.
Conclusions: SNPs associated with
chemo-response in ovarian cancer within TGCA database were not validated
in a larger database of patients and controls from OCAC. New strategies
integrating somatic and germline information may help to characterize
genetic predictors for treatment response in ovarian cancer.
Validation of the association between chemo-response and these 19 SNPs was performed using the OCAC database. Within the OCAC database, over 2,500 patients with treatment for serous ovarian cancer were identified, but none of the mentioned SNPs were significant for the outcome of interest. This indicates that while individual SNPs may not be significantly associated with the outcome, further analysis of downstream gene expression profiling and pathways are nevertheless potentially useful in a validated predictive algorithm.
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