Cargando…
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
SIMPLE SUMMARY: Heritable rare high- and moderate-risk mutations in breast cancer susceptibility genes are known of, alongside 170 common genetic low risk variants with a minor increase in risk. However, based on genetic studies, we know that over half of the breast cancer heritability is still unex...
Autores principales: | , , , , , , , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2022
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8909613/ https://www.ncbi.nlm.nih.gov/pubmed/35267517 http://dx.doi.org/10.3390/cancers14051206 |
_version_ | 1784666219914199040 |
---|---|
author | 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 |
author_facet | 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 |
author_sort | Barnekow, Elin |
collection | PubMed |
description | SIMPLE SUMMARY: Heritable rare high- and moderate-risk mutations in breast cancer susceptibility genes are known of, alongside 170 common genetic low risk variants with a minor increase in risk. However, based on genetic studies, we know that over half of the breast cancer heritability is still unexplained. By analyzing combinations of chromosomal nearby variants, so-called haplotypes, and their association to breast cancer we could identify a novel genetic breast cancer risk locus on chromosome 8 and confirm three well known low risk loci on Chr 10, 11 and 16. 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. |
format | Online Article Text |
id | pubmed-8909613 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-89096132022-03-11 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 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 Cancers (Basel) Article SIMPLE SUMMARY: Heritable rare high- and moderate-risk mutations in breast cancer susceptibility genes are known of, alongside 170 common genetic low risk variants with a minor increase in risk. However, based on genetic studies, we know that over half of the breast cancer heritability is still unexplained. By analyzing combinations of chromosomal nearby variants, so-called haplotypes, and their association to breast cancer we could identify a novel genetic breast cancer risk locus on chromosome 8 and confirm three well known low risk loci on Chr 10, 11 and 16. 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. MDPI 2022-02-25 /pmc/articles/PMC8909613/ /pubmed/35267517 http://dx.doi.org/10.3390/cancers14051206 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article 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 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 |
title | 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 |
title_full | 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 |
title_fullStr | 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 |
title_full_unstemmed | 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 |
title_short | 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 |
title_sort | 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 |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8909613/ https://www.ncbi.nlm.nih.gov/pubmed/35267517 http://dx.doi.org/10.3390/cancers14051206 |
work_keys_str_mv | AT barnekowelin aswedishgenomewidehaplotypeassociationanalysisidentifiesanovelbreastcancersusceptibilitylocusin8p212andcharacterizesthreelocionchromosomes1011and16 AT liuwen aswedishgenomewidehaplotypeassociationanalysisidentifiesanovelbreastcancersusceptibilitylocusin8p212andcharacterizesthreelocionchromosomes1011and16 AT helgadottirhafdist aswedishgenomewidehaplotypeassociationanalysisidentifiesanovelbreastcancersusceptibilitylocusin8p212andcharacterizesthreelocionchromosomes1011and16 AT michailidoukyriaki aswedishgenomewidehaplotypeassociationanalysisidentifiesanovelbreastcancersusceptibilitylocusin8p212andcharacterizesthreelocionchromosomes1011and16 AT dennisjoe aswedishgenomewidehaplotypeassociationanalysisidentifiesanovelbreastcancersusceptibilitylocusin8p212andcharacterizesthreelocionchromosomes1011and16 AT bryantpatrick aswedishgenomewidehaplotypeassociationanalysisidentifiesanovelbreastcancersusceptibilitylocusin8p212andcharacterizesthreelocionchromosomes1011and16 AT thutkawkorapinjessada aswedishgenomewidehaplotypeassociationanalysisidentifiesanovelbreastcancersusceptibilitylocusin8p212andcharacterizesthreelocionchromosomes1011and16 AT wendtcamilla aswedishgenomewidehaplotypeassociationanalysisidentifiesanovelbreastcancersusceptibilitylocusin8p212andcharacterizesthreelocionchromosomes1011and16 AT czenekamila aswedishgenomewidehaplotypeassociationanalysisidentifiesanovelbreastcancersusceptibilitylocusin8p212andcharacterizesthreelocionchromosomes1011and16 AT hallper aswedishgenomewidehaplotypeassociationanalysisidentifiesanovelbreastcancersusceptibilitylocusin8p212andcharacterizesthreelocionchromosomes1011and16 AT margolinsara aswedishgenomewidehaplotypeassociationanalysisidentifiesanovelbreastcancersusceptibilitylocusin8p212andcharacterizesthreelocionchromosomes1011and16 AT lindblomannika aswedishgenomewidehaplotypeassociationanalysisidentifiesanovelbreastcancersusceptibilitylocusin8p212andcharacterizesthreelocionchromosomes1011and16 AT barnekowelin swedishgenomewidehaplotypeassociationanalysisidentifiesanovelbreastcancersusceptibilitylocusin8p212andcharacterizesthreelocionchromosomes1011and16 AT liuwen swedishgenomewidehaplotypeassociationanalysisidentifiesanovelbreastcancersusceptibilitylocusin8p212andcharacterizesthreelocionchromosomes1011and16 AT helgadottirhafdist swedishgenomewidehaplotypeassociationanalysisidentifiesanovelbreastcancersusceptibilitylocusin8p212andcharacterizesthreelocionchromosomes1011and16 AT michailidoukyriaki swedishgenomewidehaplotypeassociationanalysisidentifiesanovelbreastcancersusceptibilitylocusin8p212andcharacterizesthreelocionchromosomes1011and16 AT dennisjoe swedishgenomewidehaplotypeassociationanalysisidentifiesanovelbreastcancersusceptibilitylocusin8p212andcharacterizesthreelocionchromosomes1011and16 AT bryantpatrick swedishgenomewidehaplotypeassociationanalysisidentifiesanovelbreastcancersusceptibilitylocusin8p212andcharacterizesthreelocionchromosomes1011and16 AT thutkawkorapinjessada swedishgenomewidehaplotypeassociationanalysisidentifiesanovelbreastcancersusceptibilitylocusin8p212andcharacterizesthreelocionchromosomes1011and16 AT wendtcamilla swedishgenomewidehaplotypeassociationanalysisidentifiesanovelbreastcancersusceptibilitylocusin8p212andcharacterizesthreelocionchromosomes1011and16 AT czenekamila swedishgenomewidehaplotypeassociationanalysisidentifiesanovelbreastcancersusceptibilitylocusin8p212andcharacterizesthreelocionchromosomes1011and16 AT hallper swedishgenomewidehaplotypeassociationanalysisidentifiesanovelbreastcancersusceptibilitylocusin8p212andcharacterizesthreelocionchromosomes1011and16 AT margolinsara swedishgenomewidehaplotypeassociationanalysisidentifiesanovelbreastcancersusceptibilitylocusin8p212andcharacterizesthreelocionchromosomes1011and16 AT lindblomannika swedishgenomewidehaplotypeassociationanalysisidentifiesanovelbreastcancersusceptibilitylocusin8p212andcharacterizesthreelocionchromosomes1011and16 |