Fine scale mapping of the 17q22 breast cancer locus using dense SNPs, genotyped within the Collaborative Oncological Gene-Environment Study (COGs).

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
Hatef Darabi Jonathan Beesley Arnaud Droit Siddhartha Kar Silje Nord Mahdi Moradi Marjaneh Penny Soucy Kyriaki Michailidou Maya Ghoussaini Hanna Fues Wahl Manjeet K Bolla Qin Wang Joe Dennis M Rosario Alonso Irene L Andrulis Hoda Anton-Culver Volker Arndt Matthias W Beckmann Javier Benitez Natalia V Bogdanova Stig E Bojesen Hiltrud Brauch Hermann Brenner Annegien Broeks Thomas Brüning Barbara Burwinkel Jenny Chang-Claude Ji-Yeob Choi Don M Conroy Fergus J Couch Angela Cox Simon S Cross Kamila Czene Peter Devilee Thilo Dörk Douglas F Easton Peter A Fasching Olivia Fletcher Henrik Flyger Eva Galle Montserrat García-Closas Graham G Giles Mark S Goldberg Anna González-Neira Pascal Guénel Christopher A Haiman Emily Hallberg Ute Hamann Mikael Hartman Antoinette Hollestelle John L Hopper Hidemi Ito Anna Jakubowska Nichola Johnson Daehee Kang Sofia Khan Veli-Matti Kosma Mieke Kriege Vessela Kristensen Diether Lambrechts Loic Le Marchand Soo Chin Lee Annika Lindblom Artitaya Lophatananon Jan Lubinski Arto Mannermaa Siranoush Manoukian Sara Margolin Keitaro Matsuo Rebecca Mayes James McKay Alfons Meindl Roger L Milne Kenneth Muir Susan L Neuhausen Heli Nevanlinna Curtis Olswold Nick Orr Paolo Peterlongo Guillermo Pita Katri Pylkäs Anja Rudolph Suleeporn Sangrajrang Elinor J Sawyer Marjanka K Schmidt Rita K Schmutzler Caroline Seynaeve Mitul Shah Chen-Yang Shen Xiao-Ou Shu Melissa C Southey Daniel O Stram Harald Surowy Anthony Swerdlow Soo H Teo Daniel C Tessier Ian Tomlinson Diana Torres Thérèse Truong Celine M Vachon Daniel Vincent Robert Winqvist Anna H Wu Pei-Ei Wu Cheng Har Yip Wei Zheng Paul D P Pharoah Per Hall Stacey L Edwards Jacques Simard Juliet D French Georgia Chenevix-Trench Alison M Dunning

Sci Rep 2016 09 7;6:32512. Epub 2016 Sep 7.

Centre for Cancer Genetic Epidemiology, Department of Oncology, University of Cambridge, Cambridge, UK.

Genome-wide association studies have found SNPs at 17q22 to be associated with breast cancer risk. To identify potential causal variants related to breast cancer risk, we performed a high resolution fine-mapping analysis that involved genotyping 517 SNPs using a custom Illumina iSelect array (iCOGS) followed by imputation of genotypes for 3,134 SNPs in more than 89,000 participants of European ancestry from the Breast Cancer Association Consortium (BCAC). We identified 28 highly correlated common variants, in a 53 Kb region spanning two introns of the STXBP4 gene, that are strong candidates for driving breast cancer risk (lead SNP rs2787486 (OR = 0.92; CI 0.90-0.94; P = 8.96 × 10(-15))) and are correlated with two previously reported risk-associated variants at this locus, SNPs rs6504950 (OR = 0.94, P = 2.04 × 10(-09), r(2) = 0.73 with lead SNP) and rs1156287 (OR = 0.93, P = 3.41 × 10(-11), r(2) = 0.83 with lead SNP). Analyses indicate only one causal SNP in the region and several enhancer elements targeting STXBP4 are located within the 53 kb association signal. Expression studies in breast tumor tissues found SNP rs2787486 to be associated with increased STXBP4 expression, suggesting this may be a target gene of this locus.

Download full-text PDF

Source
http://dx.doi.org/10.1038/srep32512DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5013272PMC
September 2016
198 Reads
3 Citations
5.080 Impact Factor

Publication Analysis

Top Keywords

breast cancer
20
cancer risk
12
lead snp
12
snp rs2787486
8
breast
6
cancer
5
snp
5
snps
5
gene strong
4
stxbp4 gene
4
strong candidates
4
driving breast
4
candidates driving
4
risk lead
4
or = 092 090-094
4
reported risk-associated
4
risk-associated variants
4
variants locus
4
correlated reported
4
p = 896 × 10-15 correlated
4

References

(Supplied by CrossRef)

J Ferlay et al.
Int J Cancer 2010

J Ferlay et al.
Int J Cancer 2015

S Ahmed et al.
Nat Genet 2009

C Turnbull et al.
Nat Genet 2010

D Campa et al.
J Natl Cancer Inst 2011

A Broeks et al.
Hum Mol Genet 2011

L Tang et al.
Arch Med Res 2012

K Michailidou et al.
Nat Genet 2013

BN Howie et al.
PLoS genetics 2009

B Howie et al.
G3 2011

Similar Publications