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Cross-Cancer Genome-Wide Association Study of Endometrial Cancer and Epithelial Ovarian Cancer Identifies Genetic Risk Regions Associated with Risk of Both Cancers
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- Glubb, Dylan M (author)
- QIMR Berghofer Medical Research Institute
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- Olsson, Håkan (author)
- Lund University,Lunds universitet,Medicinsk onkologi,Sektion I,Institutionen för kliniska vetenskaper, Lund,Medicinska fakulteten,Tumörmikromiljö,Institutionen för kliniska vetenskaper, Lund,LUCC: Lunds universitets cancercentrum,Övriga starka forskningsmiljöer,Biomarkörer och Epi,Institutionen för kliniska vetenskaper, Lund,Medical oncology,Section I,Department of Clinical Sciences, Lund,Faculty of Medicine,Tumor microenvironment,Department of Clinical Sciences, Lund,LUCC: Lund University Cancer Centre,Other Strong Research Environments,Biomarkers and epidemiology,Department of Clinical Sciences, Lund
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- O’Mara, Tracy A. (author)
- QIMR Berghofer Medical Research Institute
- (creator_code:org_t)
- 2021
- 2021
- English.
- In: Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology. - 1538-7755. ; 30:1, s. 217-228
- Journal article (peer-reviewed)
Abstract
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- 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 (rG = 0.43, P = 2.66 × 10-5). We found seven loci associated with risk for both cancers (PBonferroni < 2.4 × 10-9). In addition, four novel subgenome-wide regions at 7p22.2, 7q22.1, 9p12, and 11q13.3 were identified (P < 5 × 10-7). Promoter-associated HiChIP chromatin loops from immortalized endometrium and ovarian cell lines and expression quantitative trait loci data highlighted candidate target genes for further investigation.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.
Subject headings
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Cancer och onkologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Cancer and Oncology (hsv//eng)
- MEDICIN OCH HÄLSOVETENSKAP -- Hälsovetenskap -- Folkhälsovetenskap, global hälsa, socialmedicin och epidemiologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Health Sciences -- Public Health, Global Health, Social Medicine and Epidemiology (hsv//eng)
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