Identification and characterization of novel associations in the CASP8/ALS2CR12 region on chromosome 2 with breast cancer risk.

Authors:
Dr. Jonine Figueroa, PhD
Dr. Jonine Figueroa, PhD
Usher Institute of Population Health Sciences and Informatics
Chancellor's Fellow
Molecular epidemiology
Edinburgh, Scotland | United Kingdom
Dr. Keun-Young Yoo, MD, PhD
Dr. Keun-Young Yoo, MD, PhD
Seoul National University College of Medicine
Professor
Cancer Epidemiology
Seoul | South Korea
Wei-Yu Lin Nicola J Camp Maya Ghoussaini Jonathan Beesley Kyriaki Michailidou John L Hopper Carmel Apicella Melissa C Southey Jennifer Stone Marjanka K Schmidt Annegien Broeks Laura J Van't Veer Emiel J Th Rutgers Kenneth Muir Artitaya Lophatananon Sarah Stewart-Brown Pornthep Siriwanarangsan Peter A Fasching Lothar Haeberle Arif B Ekici Matthias W Beckmann Julian Peto Isabel Dos-Santos-Silva Olivia Fletcher Nichola Johnson Manjeet K Bolla Qin Wang Joe Dennis Elinor J Sawyer Timothy Cheng Ian Tomlinson Michael J Kerin Nicola Miller Frederik Marmé Harald M Surowy Barbara Burwinkel Pascal Guénel Thérèse Truong Florence Menegaux Claire Mulot Stig E Bojesen Børge G Nordestgaard Sune F Nielsen Henrik Flyger Javier Benitez M Pilar Zamora Jose Ignacio Arias Perez Primitiva Menéndez Anna González-Neira Guillermo Pita M Rosario Alonso Nuria Alvarez Daniel Herrero Hoda Anton-Culver Hermann Brenner Aida Karina Dieffenbach Volker Arndt Christa Stegmaier Alfons Meindl Peter Lichtner Rita K Schmutzler Bertram Müller-Myhsok Hiltrud Brauch Thomas Brüning Yon-Dschun Ko Daniel C Tessier Daniel Vincent Francois Bacot Heli Nevanlinna Kristiina Aittomäki Carl Blomqvist Sofia Khan Keitaro Matsuo Hidemi Ito Hiroji Iwata Akiyo Horio Natalia V Bogdanova Natalia N Antonenkova Thilo Dörk Annika Lindblom Sara Margolin Arto Mannermaa Vesa Kataja Veli-Matti Kosma Jaana M Hartikainen Anna H Wu Chiu-Chen Tseng David Van Den Berg Daniel O Stram Patrick Neven Els Wauters Hans Wildiers Diether Lambrechts Jenny Chang-Claude Anja Rudolph Petra Seibold Dieter Flesch-Janys Paolo Radice Paolo Peterlongo Siranoush Manoukian Bernardo Bonanni Fergus J Couch Xianshu Wang Celine Vachon Kristen Purrington Graham G Giles Roger L Milne Catriona Mclean Christopher A Haiman Brian E Henderson Fredrick Schumacher Loic Le Marchand Jacques Simard Mark S Goldberg France Labrèche Martine Dumont Soo Hwang Teo Cheng Har Yip Norhashimah Hassan Eranga Nishanthie Vithana Vessela Kristensen Wei Zheng Sandra Deming-Halverson Martha J Shrubsole Jirong Long Robert Winqvist Katri Pylkäs Arja Jukkola-Vuorinen Saila Kauppila Irene L Andrulis Julia A Knight Gord Glendon Sandrine Tchatchou Peter Devilee Robert A E M Tollenaar Caroline Seynaeve Christi J Van Asperen Montserrat García-Closas Jolanta Lissowska Louise Brinton Kamila Czene Hatef Darabi Mikael Eriksson Judith S Brand Maartje J Hooning Antoinette Hollestelle Ans M W Van Den Ouweland Agnes Jager Jingmei Li Jianjun Liu Keith Humphreys Xiao-Ou Shu Wei Lu Yu-Tang Gao Hui Cai Simon S Cross Malcolm W R Reed William Blot Lisa B Signorello Qiuyin Cai Paul D P Pharoah Barbara Perkins Mitul Shah Fiona M Blows Daehee Kang Dong-Young Noh Mikael Hartman Hui Miao Kee Seng Chia Thomas Choudary Putti Ute Hamann Craig Luccarini Caroline Baynes Shahana Ahmed Mel Maranian Catherine S Healey Anna Jakubowska Jan Lubinski Katarzyna Jaworska-Bieniek Katarzyna Durda Suleeporn Sangrajrang Valerie Gaborieau Paul Brennan James Mckay Susan Slager Amanda E Toland Drakoulis Yannoukakos Chen-Yang Shen Chia-Ni Hsiung Pei-Ei Wu Shian-Ling Ding Alan Ashworth Michael Jones Nick Orr Anthony J Swerdlow Helen Tsimiklis Enes Makalic Daniel F Schmidt Quang M Bui Stephen J Chanock David J Hunter Rebecca Hein Norbert Dahmen Lars Beckmann Kirsimari Aaltonen Taru A Muranen Tuomas Heikkinen Astrid Irwanto Nazneen Rahman Clare A Turnbull Quinten Waisfisz Hanne E J Meijers-Heijboer Muriel A Adank Rob B Van Der Luijt Per Hall Georgia Chenevix-Trench Alison Dunning Douglas F Easton Angela Cox

Hum Mol Genet 2015 Jan 28;24(1):285-98. Epub 2014 Aug 28.

Department of Oncology, University of Sheffield Medical School, Sheffield S10 2RX, UK

Previous studies have suggested that polymorphisms in CASP8 on chromosome 2 are associated with breast cancer risk. To clarify the role of CASP8 in breast cancer susceptibility, we carried out dense genotyping of this region in the Breast Cancer Association Consortium (BCAC). Single-nucleotide polymorphisms (SNPs) spanning a 1 Mb region around CASP8 were genotyped in 46 450 breast cancer cases and 42 600 controls of European origin from 41 studies participating in the BCAC as part of a custom genotyping array experiment (iCOGS). Missing genotypes and SNPs were imputed and, after quality exclusions, 501 typed and 1232 imputed SNPs were included in logistic regression models adjusting for study and ancestry principal components. The SNPs retained in the final model were investigated further in data from nine genome-wide association studies (GWAS) comprising in total 10 052 case and 12 575 control subjects. The most significant association signal observed in European subjects was for the imputed intronic SNP rs1830298 in ALS2CR12 (telomeric to CASP8), with per allele odds ratio and 95% confidence interval [OR (95% confidence interval, CI)] for the minor allele of 1.05 (1.03-1.07), P = 1 × 10(-5). Three additional independent signals from intronic SNPs were identified, in CASP8 (rs36043647), ALS2CR11 (rs59278883) and CFLAR (rs7558475). The association with rs1830298 was replicated in the imputed results from the combined GWAS (P = 3 × 10(-6)), yielding a combined OR (95% CI) of 1.06 (1.04-1.08), P = 1 × 10(-9). Analyses of gene expression associations in peripheral blood and normal breast tissue indicate that CASP8 might be the target gene, suggesting a mechanism involving apoptosis.

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Source
http://dx.doi.org/10.1093/hmg/ddu431DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4334820PMC
January 2015
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