NDLI: A Genome-Wide “Pleiotropy Scan” Does Not Identify New Susceptibility Loci for Estrogen Receptor Negative Breast Cancer

Content Provider	PubMed Central
Author	Campa, Daniele Barrdahl, Myrto Tsilidis, Konstantinos K. Severi, Gianluca Diver, W. Ryan Siddiq, Afshan Chanock, Stephen Hoover, Robert N. Ziegler, Regina G. Berg, Christine D. Buys, Saundra S. Haiman, Christopher A. Henderson, Brian E. Schumacher, Fredrick R. Marchand, Loïc Le Dieter, Flesch-janys Lindström, Sara Hunter, David J. Hankinson, Susan E. Willett, Walter C. Kraft, Peter Cox, David G. Khaw, Kay-tee Anne, Tjønneland Laure, Dossus Trichopoulos, Dimitrios Panico, Salvatore Gils, Carla H. Van Weiderpass, Elisabete Barricarte, Aurelio Sund, Malin Gaudet, Mia M. Giles, Graham Southey, Melissa Baglietto, Laura Jenny, Chang-claude Rudolf, Kaaks Canzian, Federico
Editor	Paolo, Peterlongo
Copyright Year	2014
Abstract	Approximately 15–30% of all breast cancer tumors are estrogen receptor negative (ER−). Compared with ER-positive (ER+) disease they have an earlier age at onset and worse prognosis. Despite the vast number of risk variants identified for numerous cancer types, only seven loci have been unambiguously identified for ER-negative breast cancer. With the aim of identifying new susceptibility SNPs for this disease we performed a pleiotropic genome-wide association study (GWAS). We selected 3079 SNPs associated with a human complex trait or disease at genome-wide significance level (P<5×10−8) to perform a secondary analysis of an ER-negative GWAS from the National Cancer Institute's Breast and Prostate Cancer Cohort Consortium (BPC3), including 1998 cases and 2305 controls from prospective studies. We then tested the top ten associations (i.e. with the lowest P-values) using three additional populations with a total sample size of 3509 ER+ cases, 2543 ER− cases and 7031 healthy controls. None of the 3079 selected variants in the BPC3 ER-GWAS were significant at the adjusted threshold. 186 variants were associated with ER− breast cancer risk at a conventional threshold of P<0.05, with P-values ranging from 0.049 to 2.3×10−4. None of the variants reached statistical significance in the replication phase. In conclusion, this study did not identify any novel susceptibility loci for ER-breast cancer using a “pleiotropic approach”.
Related Links	http://dx.doi.org/10.1371/journal.pone.0085955
Starting Page	85955
File Format	PDF
ISSN	19326203
e-ISSN	19326203
Journal	PLoS ONE
Issue Number	2
Volume Number	9
Language	English
Publisher	Public Library of Science
Publisher Date	2014-02-01
Access Restriction	Open
Rights Holder	Public Library of Science
Subject Keyword	Biochemistry, Genetics and Molecular Biology(all) Agricultural and Biological Sciences(all) Medicine(all) Research in Higher Education
Content Type	Text
Resource Type	Article
Subject	Multidisciplinary

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