TY - JOUR
T1 - Cross-Cancer Genome-Wide Association Study of Endometrial Cancer and Epithelial Ovarian Cancer Identifies Genetic Risk Regions Associated with Risk of Both Cancers
AU - AOCS Group
AU - AOCS Group
AU - Glubb, Dylan M.
AU - Thompson, Deborah J.
AU - Aben, Katja K.H.
AU - Alsulimani, Ahmad
AU - Amant, Frederic
AU - Annibali, Daniela
AU - Attia, John
AU - Barricarte, Aurelio
AU - Beckmann, Matthias W.
AU - Berchuck, Andrew
AU - Bermisheva, Marina
AU - Bernardini, Marcus Q.
AU - Bischof, Katharina
AU - Bjorge, Line
AU - Bodelon, Clara
AU - Brand, Alison H.
AU - Brenton, James D.
AU - Brinton, Louise A.
AU - Bruinsma, Fiona
AU - Buchanan, Daniel D.
AU - Burghaus, Stefanie
AU - Butzow, Ralf
AU - Cai, Hui
AU - Carney, Michael E.
AU - Chanock, Stephen J.
AU - Chen, Chu
AU - Chen, Xiao Qing
AU - Chen, Zhihua
AU - Cook, Linda S.
AU - Cunningham, Julie M.
AU - De Vivo, Immaculata
AU - deFazio, Anna
AU - Doherty, Jennifer A.
AU - Dörk, Thilo
AU - du Bois, Andreas
AU - Dunning, Alison M.
AU - Dürst, Matthias
AU - Edwards, Todd
AU - Edwards, Robert P.
AU - Ekici, Arif B.
AU - Ewing, Ailith
AU - Fasching, Peter A.
AU - Ferguson, Sarah
AU - Flanagan, James M.
AU - Fostira, Florentia
AU - Fountzilas, George
AU - Friedenreich, Christine M.
AU - Gao, Bo
AU - Pejovic, Tanja
AU - Sellers, Thomas A.
N1 - Publisher Copyright:
© 2020 American Association for Cancer Research.
PY - 2021/1/1
Y1 - 2021/1/1
N2 - 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.
AB - 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.
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U2 - 10.1158/1055-9965.EPI-20-0739
DO - 10.1158/1055-9965.EPI-20-0739
M3 - Article
C2 - 33144283
AN - SCOPUS:85122168882
SN - 1055-9965
VL - 30
SP - 217
EP - 228
JO - Cancer Epidemiology Biomarkers and Prevention
JF - Cancer Epidemiology Biomarkers and Prevention
IS - 1
ER -