A Swedish genome-wide haplotype association analysis identifies novel candidate loci associated with endometrial cancer risk
Barnekow E, Liu W, Andersson E, Wang X, Helgadottir HT, Thutkawkorapin J, Barilla S, Vermani L, Mints M, Tham E, Fasching P, Lambrechts D, Amant F, Spurdle AB, Hall P, O’Mara TA, Margolin S, Lindblom A (2025)
Publication Type: Journal article
Publication year: 2025
Journal
Book Volume: 20
Article Number: e0316086
Journal Issue: 3 March
DOI: 10.1371/journal.pone.0316086
Abstract
Genome-wide association studies [GWAS] have identified a limited number of endometrial cancer risk loci by analyzing single nucleotide polymorphisms [SNPs]. We hypothesized that analyzing haplotypes rather than SNPs could provide novel and more detailed information on genetic cancer susceptibility loci. To examine the association of a SNP or haplotype with endometrial cancer risk we performed a two-stage haplotype GWAS. The discovery GWAS included a sub-cohort of 1,116 Swedish endometrial cancer cases and 5,021 controls from previously published GWAS data. A sliding window analysis was employed with window sizes of 1-25 SNPs using a logistic regression model. The Swedish haplotype analysis identified 15 novel candidate risk loci (2q31.1, 4p16.1, 4p15.31, 6q13, 7p21.1, 9p13.3, 10q26.3, 11q21, 12q13.11, 13q12.11, 15q13.3, 16q24.3, 19q13.32, 20p12.3 and 22q13.2) with OR ranging from 1.6 to 3.3 and p-values from 4.25 × 10−8 to 9.86 × 10−15. A second replication haplotype analysis of the Swedish novel loci was performed using two cohorts from Belgium and Germany. In spite of small sample sizes in the replication cohorts, there was still support for most loci with positive ORs. In addition, the findings in the two European cohorts motivates further studies to search for founder haplotypes. These novel findings suggested that endometrial cancer loci, identified through haplotype analysis, conferred a higher risk compared to previous single-variant GWAS.
Authors with CRIS profile
Involved external institutions
Karolinska Institute
Sweden (SE)
Karolinska University Hospital / Karolinska Universitetssjukhuset
Sweden (SE)
QIMR Berghofer Medical Research Institute (früher: the Queensland Institute of Medical Research)
Australia (AU)
Katholieke Universiteit Leuven (KUL) / Catholic University of Leuven
Belgium (BE)
University Hospital Leuven (UZ) / Universitaire ziekenhuizen Leuven
Belgium (BE)
Södersjukhuset
Sweden (SE)
Sweden (SE)
Karolinska University Hospital / Karolinska Universitetssjukhuset
Sweden (SE)
QIMR Berghofer Medical Research Institute (früher: the Queensland Institute of Medical Research)
Australia (AU)
Katholieke Universiteit Leuven (KUL) / Catholic University of Leuven
Belgium (BE)
University Hospital Leuven (UZ) / Universitaire ziekenhuizen Leuven
Belgium (BE)
Södersjukhuset
Sweden (SE)
How to cite
APA:
Barnekow, E., Liu, W., Andersson, E., Wang, X., Helgadottir, H.T., Thutkawkorapin, J.,... Lindblom, A. (2025). A Swedish genome-wide haplotype association analysis identifies novel candidate loci associated with endometrial cancer risk. PLoS ONE, 20(3 March). https://doi.org/10.1371/journal.pone.0316086
MLA:
Barnekow, Elin, et al. "A Swedish genome-wide haplotype association analysis identifies novel candidate loci associated with endometrial cancer risk." PLoS ONE 20.3 March (2025).
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