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

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

(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 st...

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Bibliographic Details
Published in:Cancers 2022, Vol.14 (5), p.1206
Main Authors: Barnekow, Elin, Liu, Wen, Helgadottir, Hafdis T, Michailidou, Kyriaki, Dennis, Joe, Bryant, Patrick, Thutkawkorapin, Jessada, Wendt, Camilla, Czene, Kamila, Hall, Per, Margolin, Sara, Lindblom, Annika
Format: Article
Language:eng
Subjects:
Association analysis
BNIP3L
Breast cancer
Cancer och onkologi
CASC16
Chromosome 10
Chromosome 11
Chromosome 8
Chromosomes
Collaboration
Colorectal cancer
Consortia
Datasets
FGFR2
Genomes
Genotype & phenotype
GWAS
haplotype
Haplotypes
Heritability
Klinisk medicin
Mammography
Medicin och hälsovetenskap
Medicinsk genetik
Medicinska och farmaceutiska grundvetenskaper
Population
Population studies
Quality control
Single-nucleotide polymorphism
Susceptibility
TOX3
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Summary:(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.
ISSN:2072-6694
2072-6694