Association analysis of a chemo-response signature identified within The Cancer Genome Atlas aimed at predicting genetic risk for chemo-response in ovarian cancer.
Erin A Salinas, Andreea M Newtson, Kimberly K Leslie, Jesus Gonzalez-Bosquet
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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.
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