A Swedish Genome-Wide Haplotype Association Analysis Identifies a Novel Breast Cancer Susceptibility Locus in 8p21.2 and Characterizes Three Loci on Chromosomes 10, 11 and 16.
Authors
Liu, Wen
Bryant, Patrick
Thutkawkorapin, Jessada
Wendt, Camilla
Czene, Kamila
Margolin, Sara
Publication Date
2022-02-25Journal Title
Cancers (Basel)
ISSN
2072-6694
Publisher
MDPI AG
Volume
14
Issue
5
Language
en
Type
Article
This Version
VoR
Metadata
Show full item recordCitation
Barnekow, E., Liu, W., Helgadottir, H. T., Michailidou, K., Dennis, J., Bryant, P., Thutkawkorapin, J., et al. (2022). A Swedish Genome-Wide Haplotype Association Analysis Identifies a Novel Breast Cancer Susceptibility Locus in 8p21.2 and Characterizes Three Loci on Chromosomes 10, 11 and 16.. Cancers (Basel), 14 (5) https://doi.org/10.3390/cancers14051206
Abstract
(1) Background: The heritability of breast cancer is partly explained but much of the genetic contribution remains to be identified. Haplotypes are often used as markers of ethnicity as they are preserved through generations. We have previously demonstrated that haplotype analysis, in addition to standard SNP association studies, could give novel and more detailed information on genetic cancer susceptibility. (2) Methods: In order to examine the association of a SNP or a haplotype to breast cancer risk, we performed a genome wide haplotype association study, using sliding window analysis of window sizes 1-25 and 50 SNPs, in 3200 Swedish breast cancer cases and 5021 controls. (3) Results: We identified a novel breast cancer susceptibility locus in 8p21.1 (OR 2.08; p 3.92 × 10-8), confirmed three known loci in 10q26.13, 11q13.3, 16q12.1-2 and further identified novel subloci within these three loci. Altogether 76 risk SNPs, 3302 risk haplotypes of window size 2-25 and 113 risk haplotypes of window size 50 at p < 5 × 10-8 on chromosomes 8, 10, 11 and 16 were identified. In the known loci haplotype analysis reached an OR of 1.48 in overall breast cancer and in familial cases OR 1.68. (4) Conclusions: Analyzing haplotypes, rather than single variants, could detect novel susceptibility loci even in small study populations but the method requires a fairly homogenous study population.
Keywords
BNIP3L, FGFR2, TOX3, CASC16, breast cancer, GWAS, haplotype
Sponsorship
Swedish Cancer Society (18-0700)
Swedish Research Council (2019-01441)
Radium Hemmets Research Funds (191203)
Stockholm County Council (500395)
Märit and Hans Rausing´s Initiative Against Breast Cancer (-)
Identifiers
External DOI: https://doi.org/10.3390/cancers14051206
This record's URL: https://www.repository.cam.ac.uk/handle/1810/334581
Rights
Licence:
https://creativecommons.org/licenses/by/4.0/
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