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Fine-scale mapping of 8q24 locus identifies multiple independent risk variants for breast cancer.

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Date
2016-09
ICR Author
Fletcher, Olivia
Swerdlow, Anthony
Orr, Nicholas
Author
Shi, J
Zhang, Y
Zheng, W
Michailidou, K
Ghoussaini, M
Bolla, MK
Wang, Q
Dennis, J
Lush, M
Milne, RL
Shu, X-O
Beesley, J
Kar, S
Andrulis, IL
Anton-Culver, H
Arndt, V
Beckmann, MW
Zhao, Z
Guo, X
Benitez, J
Beeghly-Fadiel, A
Blot, W
Bogdanova, NV
Bojesen, SE
Brauch, H
Brenner, H
Brinton, L
Broeks, A
Brüning, T
Burwinkel, B
Cai, H
Canisius, S
Chang-Claude, J
Choi, J-Y
Couch, FJ
Cox, A
Cross, SS
Czene, K
Darabi, H
Devilee, P
Droit, A
Dork, T
Fasching, PA
Fletcher, O
Flyger, H
Fostira, F
Gaborieau, V
García-Closas, M
Giles, GG
Mervi Grip
Guenel, P
Haiman, CA
Hamann, U
Hartman, M
Miao, H
Hollestelle, A
Hopper, JL
Hsiung, C-N
kConFab Investigators
Ito, H
Jakubowska, A
Johnson, N
Torres, D
Kabisch, M
Kang, D
Khan, S
Knight, JA
Kosma, V-M
Lambrechts, D
Li, J
Lindblom, A
Lophatananon, A
Lubinski, J
Mannermaa, A
Manoukian, S
Le Marchand, L
Margolin, S
Marme, F
Matsuo, K
McLean, C
Meindl, A
Muir, K
Neuhausen, SL
Nevanlinna, H
Nord, S
Børresen-Dale, A-L
Olson, JE
Orr, N
van den Ouweland, AMW
Peterlongo, P
Putti, TC
Rudolph, A
Sangrajrang, S
Sawyer, EJ
Schmidt, MK
Schmutzler, RK
Shen, C-Y
Hou, M-F
Shrubsole, MJ
Southey, MC
Swerdlow, A
Teo, SH
Thienpont, B
Toland, AE
Tollenaar, RAEM
Tomlinson, I
Truong, T
Tseng, C-C
Wen, W
Winqvist, R
Wu, AH
Yip, CH
Zamora, PM
Zheng, Y
Floris, G
Cheng, C-Y
Hooning, MJ
Martens, JWM
Seynaeve, C
Kristensen, VN
Hall, P
Pharoah, PDP
Simard, J
Chenevix-Trench, G
Dunning, AM
Antoniou, AC
Easton, DF
Cai, Q
Long, J
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Type
Journal Article
Metadata
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Abstract
Previous genome-wide association studies among women of European ancestry identified two independent breast cancer susceptibility loci represented by single nucleotide polymorphisms (SNPs) rs13281615 and rs11780156 at 8q24. A fine-mapping study across 2.06 Mb (chr8:127,561,724-129,624,067, hg19) in 55,540 breast cancer cases and 51,168 controls within the Breast Cancer Association Consortium was conducted. Three additional independent association signals in women of European ancestry, represented by rs35961416 (OR = 0.95, 95% CI = 0.93-0.97, conditional p = 5.8 × 10(-6) ), rs7815245 (OR = 0.94, 95% CI = 0.91-0.96, conditional p = 1.1 × 10(-6) ) and rs2033101 (OR = 1.05, 95% CI = 1.02-1.07, conditional p = 1.1 × 10(-4) ) were found. Integrative analysis using functional genomic data from the Roadmap Epigenomics, the Encyclopedia of DNA Elements project, the Cancer Genome Atlas and other public resources implied that SNPs rs7815245 in Signal 3, and rs1121948 in Signal 5 (in linkage disequilibrium with rs11780156, r(2)  = 0.77), were putatively functional variants for two of the five independent association signals. The results highlighted multiple 8q24 variants associated with breast cancer susceptibility in women of European ancestry.
URI
https://repository.icr.ac.uk/handle/internal/159
DOI
https://doi.org/10.1002/ijc.30150
Collections
  • Breast Cancer Research
  • Genetics and Epidemiology
Subject
Mervi Grip
kConFab Investigators
Chromosomes, Human, Pair 8
Humans
Breast Neoplasms
Odds Ratio
Risk
Case-Control Studies
Chromosome Mapping
Genotype
Haplotypes
Linkage Disequilibrium
Polymorphism, Single Nucleotide
Alleles
Quantitative Trait Loci
European Continental Ancestry Group
Female
Genetic Variation
Genome-Wide Association Study
Research team
Complex Trait Genetics
Functional Genetic Epidemiology
Aetiological Epidemiology
Language
eng
Date accepted
2016-01-19
License start date
2016-09
Citation
International journal of cancer, 2016, 139 (6), pp. 1303 - 1317

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