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Figure 1. Flowchart of a GWAS Study GWAS with specific phenotype Identify SNPs Identify SNP function Relate SNPs to genes and regulate estradiol-dependent induction of BRCA1. He also emphasized that SERMS can reverse that SNPdependent expression. In summary, Dr Ingle emphasized that a GWAS is the starting point for a process that examines how an SNP works, how it relates to specific genes, and how these genes then influence the effect of the drug on a clinical phenotype. While pharmacogenomics studies have identified new biology and have substantial potential to provide clinical benefit, further work is needed to validate the clinical relevance and value of this approach. Relate to clinical phenotype GWAS, genome-wide association study; SNP, single-nucleotide polymorphism. Reproduced with permission from JN Ingle, MD. Dr Ingle closed his talk by highlighting genetic research regarding the use of selective estrogen receptor modulators (SERMs) to prevent BC. To date, the two largest SERM BC prevention trials are the National Surgical Adjuvant Breast and Bowel Project (NSABP) P-1 trial of tamoxifen [Fisher B et al. J Natl Cancer Inst. 1998] and the NSABP P-2 trial that compared raloxifene with tamoxifen [Vogel VG et al. Cancer Prev Res (Phila). 2010]. Combined, these studies involved > 32 000 women and were the basis of the 2 drugs being approved by the US Food and Drug Administration to prevent BC [Ingle JN et al. Cancer Discov. 2013]. While these trials confirmed that 5 years of treatment with raloxifene and tamoxifen could reduce the recurrence of BC by one-half, the drugs are not routinely used for this indication. This is due in part to the high number of patients needed to treat to prevent one case of BC and because the SERMs can be associated with worrisome side effects. Dr Ingle and his colleagues performed a GWAS that included 592 cases and 1171 controls from the NBASP P-1 and P-2 trials [Ingle JN et al. Cancer Discov. 2013]. A ZNF423 SNP variant on chromosome 16 was associated with lower breast cancer risk (OR = 0.7), and these variant SNPs were found to be an estrogen-inducible BRCA1 transcription factor. A CTSO SNP variant on chromosome 4 was associated with an increased risk of developing BC (OR = 1.42) and was found to disrupt the estrogen receptor element. The combined odds ratios for these 2 sets of SNPs suggest a broad range of relative odds ratios for the development of BC for women on SERM therapy for 5 years. Dr Ingle highlighted the fact that both the CTSO and the ZNF43 SNPs appear to be estrogen inducible The editors would like to thank the many members of the ENDO 2015 presenting faculty who generously gave their time to ensure the accuracy and quality of the articles in this publication. Official Peer-Reviewed Highlights From ENDO 2015 3

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MD Conference Express - ENDO 2015

MD Conference Express - ENDO 2015 - (Page Cover1)
MD Conference Express - ENDO 2015 - (Page Cover2)
MD Conference Express - ENDO 2015 - (Page i)
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MD Conference Express - ENDO 2015 - Contents (Page 1)
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