Clinical Research Papers:
The identification of trans-associations between prostate cancer GWAS SNPs and RNA expression differences in tumor-adjacent stroma
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Xin Chen1, Michael McClelland2,3, Zhenyu Jia2,4,5, Farah B. Rahmatpanah2, Anne Sawyers2, Jeffrey Trent6, David Duggan7, Dan Mercola2
1Genomics Center, Loma Linda University, Loma Linda, California, 92354, United States of America
2Department of Pathology and Laboratory Medicine, University of California, Irvine, California, 92697, United States of America
3Department of Microbiology and Molecular Genetics, University of California, Irvine, California, 92697, United States of America
4Department of Statistics, The University of Akron, Akron, Ohio, 44325, United States of America
5Department of Family & Community Medicine, Northeast Ohio Medical University, Rootstown, Ohio, 44272, United States of America
6Genetic Basis of Human Disease Division, The Translational Genomics Research Institute, Phoenix, Arizona, 85004, United States of America
7Integrated Cancer Genomics Division, The Translational Genomics Research Institute, Phoenix, Arizona, 85004, United States of America
Xin Chen, e-mail: [email protected]
Dan Mercola, e-mail: [email protected]
Keywords: SNPs, eQTL, prostate cancer
Received: August 14, 2014 Accepted: November 17, 2014 Published: February 09, 2015
Here we tested the hypothesis that SNPs associated with prostate cancer risk, might differentially affect RNA expression in prostate cancer stroma. The most significant 35 SNP loci were selected from Genome Wide Association (GWA) studies of ~40,000 patients. We also selected 4030 transcripts previously associated with prostate cancer diagnosis and prognosis. eQTL analysis was carried out by a modified BAYES method to analyze the associations between the risk variants and expressed transcripts jointly in a single model. We observed 47 significant associations between eight risk variants and the expression patterns of 46 genes. This is the first study to identify associations between multiple SNPs and multiple in trans gene expression differences in cancer stroma. Potentially, a combination of SNPs and associated expression differences in prostate stroma may increase the power of risk assessment for individuals, and for cancer progression.
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