Common non-synonymous SNPs associated with breast cancer susceptibility: findings from the Breast Cancer Association Consortium.

Authors:
Roger L Milne
Roger L Milne
Cancer Epidemiology Centre
Navi Mumbai | India
Barbara Burwinkel
Barbara Burwinkel
University of Heidelberg
Heidelberg | Germany
Kyriaki Michailidou
Kyriaki Michailidou
University of Cambridge
United Kingdom
M Pilar Zamora
M Pilar Zamora
Complejo Hospitalario de Toledo. rluque@sescam.jccm.es
David Hardisson
David Hardisson
Hospital Universitario La Paz
Spain
Marta Mendiola
Marta Mendiola
Hospital Universitario La Paz
Spain
Jose-Ignacio Arias-Perez Primitiva Menéndez-Rodríguez Anna González-Neira Guillermo Pita M Rosario Alonso Joe Dennis Qin Wang Manjeet K Bolla Anthony Swerdlow Alan Ashworth Nick Orr Minouk Schoemaker Yon-Dschun Ko Hiltrud Brauch Ute Hamann Irene L Andrulis Julia A Knight Gord Glendon Sandrine Tchatchou Keitaro Matsuo Hidemi Ito Hiroji Iwata Kazuo Tajima Jingmei Li Judith S Brand Hermann Brenner Aida Karina Dieffenbach Volker Arndt Christa Stegmaier Diether Lambrechts Gilian Peuteman Marie-Rose Christiaens Ann Smeets Anna Jakubowska Jan Lubinski Katarzyna Jaworska-Bieniek Katazyna Durda Mikael Hartman Miao Hui Wei Yen Lim Ching Wan Chan Federick Marme Rongxi Yang Peter Bugert Annika Lindblom Sara Margolin Montserrat García-Closas Stephen J Chanock Jolanta Lissowska Jonine D Figueroa Stig E Bojesen Børge G Nordestgaard Henrik Flyger Maartje J Hooning Mieke Kriege Ans M W van den Ouweland Linetta B Koppert Olivia Fletcher Nichola Johnson Isabel dos-Santos-Silva Julian Peto Wei Zheng Sandra Deming-Halverson Martha J Shrubsole Jirong Long Jenny Chang-Claude Anja Rudolph Petra Seibold Dieter Flesch-Janys Robert Winqvist Katri Pylkäs Arja Jukkola-Vuorinen Mervi Grip Angela Cox Simon S Cross Malcolm W R Reed Marjanka K Schmidt Annegien Broeks Sten Cornelissen Linde Braaf Daehee Kang Ji-Yeob Choi Sue K Park Dong-Young Noh Jacques Simard Martine Dumont Mark S Goldberg France Labrèche Peter A Fasching Alexander Hein Arif B Ekici Matthias W Beckmann Paolo Radice Paolo Peterlongo Jacopo Azzollini Monica Barile Elinor Sawyer Ian Tomlinson Michael Kerin Nicola Miller John L Hopper Daniel F Schmidt Enes Makalic Melissa C Southey Soo Hwang Teo Cheng Har Yip Kavitta Sivanandan Wan-Ting Tay Chen-Yang Shen Chia-Ni Hsiung Jyh-Cherng Yu Ming-Feng Hou Pascal Guénel Therese Truong Marie Sanchez Claire Mulot William Blot Qiuyin Cai Heli Nevanlinna Taru A Muranen Kristiina Aittomäki Carl Blomqvist Anna H Wu Chiu-Chen Tseng David Van Den Berg Daniel O Stram Natalia Bogdanova Thilo Dörk Kenneth Muir Artitaya Lophatananon Sarah Stewart-Brown Pornthep Siriwanarangsan Arto Mannermaa Vesa Kataja Veli-Matti Kosma Jaana M Hartikainen Xiao-Ou Shu Wei Lu Yu-Tang Gao Ben Zhang Fergus J Couch Amanda E Toland Drakoulis Yannoukakos Suleeporn Sangrajrang James McKay Xianshu Wang Janet E Olson Celine Vachon Kristen Purrington Gianluca Severi Laura Baglietto Christopher A Haiman Brian E Henderson Fredrick Schumacher Loic Le Marchand Peter Devilee Robert A E M Tollenaar Caroline Seynaeve Kamila Czene Mikael Eriksson Keith Humphreys Hatef Darabi Shahana Ahmed Mitul Shah Paul D P Pharoah Per Hall Graham G Giles Javier Benítez Alison M Dunning Georgia Chenevix-Trench Douglas F Easton

Hum Mol Genet 2014 Nov 18;23(22):6096-111. Epub 2014 Jun 18.

Centre for Cancer Genetic Epidemiology, Department of Public Health and Primary Care, Centre for Cancer Genetic Epidemiology, Department of Oncology, University of Cambridge, Cambridge, UK.

Candidate variant association studies have been largely unsuccessful in identifying common breast cancer susceptibility variants, although most studies have been underpowered to detect associations of a realistic magnitude. We assessed 41 common non-synonymous single-nucleotide polymorphisms (nsSNPs) for which evidence of association with breast cancer risk had been previously reported. Case-control data were combined from 38 studies of white European women (46 450 cases and 42 600 controls) and analyzed using unconditional logistic regression. Strong evidence of association was observed for three nsSNPs: ATXN7-K264R at 3p21 [rs1053338, per allele OR = 1.07, 95% confidence interval (CI) = 1.04-1.10, P = 2.9 × 10(-6)], AKAP9-M463I at 7q21 (rs6964587, OR = 1.05, 95% CI = 1.03-1.07, P = 1.7 × 10(-6)) and NEK10-L513S at 3p24 (rs10510592, OR = 1.10, 95% CI = 1.07-1.12, P = 5.1 × 10(-17)). The first two associations reached genome-wide statistical significance in a combined analysis of available data, including independent data from nine genome-wide association studies (GWASs): for ATXN7-K264R, OR = 1.07 (95% CI = 1.05-1.10, P = 1.0 × 10(-8)); for AKAP9-M463I, OR = 1.05 (95% CI = 1.04-1.07, P = 2.0 × 10(-10)). Further analysis of other common variants in these two regions suggested that intronic SNPs nearby are more strongly associated with disease risk. We have thus identified a novel susceptibility locus at 3p21, and confirmed previous suggestive evidence that rs6964587 at 7q21 is associated with risk. The third locus, rs10510592, is located in an established breast cancer susceptibility region; the association was substantially attenuated after adjustment for the known GWAS hit. Thus, each of the associated nsSNPs is likely to be a marker for another, non-coding, variant causally related to breast cancer risk. Further fine-mapping and functional studies are required to identify the underlying risk-modifying variants and the genes through which they act.

Download full-text PDF

Source
http://hmg.oxfordjournals.org/content/early/2014/07/04/hmg.d
Web Search
http://www.hmg.oxfordjournals.org/cgi/doi/10.1093/hmg/ddu311
Publisher Site
http://dx.doi.org/10.1093/hmg/ddu311DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4204770PMC

Still can't find the full text of the article?

We can help you send a request to the authors directly.
November 2014
167 Reads
27 Citations
6.393 Impact Factor

Publication Analysis

Top Keywords

breast cancer
24
cancer susceptibility
12
association studies
8
105 95%
8
evidence association
8
cancer risk
8
common non-synonymous
8
107 95%
8
breast
6
association
6
cancer
6
95%
5
studies
5
data genome-wide
4
genome-wide association
4
studies gwass
4
data including
4
combined analysis
4
analysis data
4
gwass atxn7-k264r
4

Altmetric Statistics

References

(Supplied by CrossRef)

Similar Publications