Cross-Cancer Genome-Wide Association Study of Endometrial Cancer and Epithelial Ovarian Cancer Identifies Genetic Risk Regions Associated with Risk of Both Cancers.
Journal
Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology
ISSN: 1538-7755
Titre abrégé: Cancer Epidemiol Biomarkers Prev
Pays: United States
ID NLM: 9200608
Informations de publication
Date de publication:
01 2021
01 2021
Historique:
received:
13
05
2020
revised:
31
07
2020
accepted:
22
10
2020
pubmed:
5
11
2020
medline:
27
11
2021
entrez:
4
11
2020
Statut:
ppublish
Résumé
Accumulating evidence suggests a relationship between endometrial cancer and ovarian cancer. Independent genome-wide association studies (GWAS) for endometrial cancer and ovarian cancer have identified 16 and 27 risk regions, respectively, four of which overlap between the two cancers. We aimed to identify joint endometrial and ovarian cancer risk loci by performing a meta-analysis of GWAS summary statistics from these two cancers. Using LDScore regression, we explored the genetic correlation between endometrial cancer and ovarian cancer. To identify loci associated with the risk of both cancers, we implemented a pipeline of statistical genetic analyses (i.e., inverse-variance meta-analysis, colocalization, and M-values) and performed analyses stratified by subtype. Candidate target genes were then prioritized using functional genomic data. Genetic correlation analysis revealed significant genetic correlation between the two cancers ( Using cross-cancer GWAS meta-analysis, we have identified several joint endometrial and ovarian cancer risk loci and candidate target genes for future functional analysis. Our research highlights the shared genetic relationship between endometrial cancer and ovarian cancer. Further studies in larger sample sets are required to confirm our findings.
Sections du résumé
BACKGROUND
Accumulating evidence suggests a relationship between endometrial cancer and ovarian cancer. Independent genome-wide association studies (GWAS) for endometrial cancer and ovarian cancer have identified 16 and 27 risk regions, respectively, four of which overlap between the two cancers. We aimed to identify joint endometrial and ovarian cancer risk loci by performing a meta-analysis of GWAS summary statistics from these two cancers.
METHODS
Using LDScore regression, we explored the genetic correlation between endometrial cancer and ovarian cancer. To identify loci associated with the risk of both cancers, we implemented a pipeline of statistical genetic analyses (i.e., inverse-variance meta-analysis, colocalization, and M-values) and performed analyses stratified by subtype. Candidate target genes were then prioritized using functional genomic data.
RESULTS
Genetic correlation analysis revealed significant genetic correlation between the two cancers (
CONCLUSIONS
Using cross-cancer GWAS meta-analysis, we have identified several joint endometrial and ovarian cancer risk loci and candidate target genes for future functional analysis.
IMPACT
Our research highlights the shared genetic relationship between endometrial cancer and ovarian cancer. Further studies in larger sample sets are required to confirm our findings.
Identifiants
pubmed: 33144283
pii: 1055-9965.EPI-20-0739
doi: 10.1158/1055-9965.EPI-20-0739
doi:
Types de publication
Journal Article
Meta-Analysis
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
217-228Subventions
Organisme : Cancer Research UK
ID : 15601
Pays : United Kingdom
Organisme : Wellcome Trust
ID : 203477/Z/16/Z
Pays : United Kingdom
Organisme : Medical Research Council
ID : MC_UU_12023/20
Pays : United Kingdom
Organisme : Medical Research Council
ID : MR/R026017/1
Pays : United Kingdom
Informations de copyright
©2020 American Association for Cancer Research.
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