دورية أكاديمية

Cross-Cancer Genome-Wide Association Study of Endometrial Cancer and Epithelial Ovarian Cancer Identifies Genetic Risk Regions Associated with Risk of Both Cancers

التفاصيل البيبلوغرافية
العنوان: Cross-Cancer Genome-Wide Association Study of Endometrial Cancer and Epithelial Ovarian Cancer Identifies Genetic Risk Regions Associated with Risk of Both Cancers
المؤلفون: Glubb, Dylan M., Thompson, Deborah J., Bermisheva, Marina, McNeish, IA, Menon, U, Modugno, F, Moysich, KB, Nevanlinna, H, Odunsi, K, Olsson, H, Orsulic, S, Osorio, A, Palli, D, Bernardini, Marcus Q., Park-Simon, T-W, Pearce, CL, Pejovic, T, Permuth, JB, Podgorska, A, Ramus, SJ, Rebbeck, TR, Riggan, MJ, Risch, HA, Rothstein, JH, Bischof, Katharina, Runnebaum, IB, Scott, RJ, Sellers, TA, Senz, J, Setiawan, VW, Siddiqui, N, Sieh, W, Spiewankiewicz, B, Sutphen, R, Swerdlow, AJ, Bjorge, Line, Szafron, LM, Teo, SH, Thompson, PJ, Thomsen, LCV, Titus, L, Tone, A, Tumino, R, Turman, C, Vanderstichele, A, Edwards, DV, Bodelon, Clara, Vergote, I, Vierkant, RA, Wang, Z, Wang-Gohrke, S, Webb, PM, White, E, Whittemore, AS, Winham, SJ, Wu, X, Wu, AH, Brand, Alison H., Yannoukakos, D, Spurdle, AB, O'Mara, TA, Brenton, James D., Brinton, Louise A., Bruinsma, Fiona, Buchanan, Daniel D., Aben, Katja K. H., Burghaus, S, Butzow, R, Cai, H, Carney, ME, Chanock, SJ, Chen, C, Chen, XQ, Chen, Z, Cook, LS, Cunningham, JM, Alsulimani, Ahmad, De Vivo, I, DeFazio, A, Doherty, JA, Dork, T, du Bois, A, Dunning, AM, Durst, M, Edwards, T, Edwards, RP, Ekici, AB, Amant, Frederic, Ewing, A, Fasching, PA, Ferguson, S, Flanagan, JM, Fostira, F, Fountzilas, G, Friedenreich, CM, Gao, B, Gaudet, MM, Gawelko, J, Annibali, Daniela, Gentry-Maharaj, A, Giles, GG, Glasspool, R, Goodman, MT, Gronwald, J, Harris, HR, Harter, P, Hein, A, Heitz, F, Hildebrandt, MAT, Attia, John, Hillemanns, P, Hogdall, E, Hogdall, CK, Holliday, Elizabeth G., Huntsman, DG, Huzarski, T, Jakubowska, A, Jensen, A, Jones, ME, Karlan, BY, Barricarte, Aurelio, Karnezis, A, Kelley, JL, Khusnutdinova, E, Killeen, JL, Kjaer, SK, Klapdor, R, Kobel, M, Konopka, B, Konstantopoulou, I, Kopperud, RK, Beckmann, Matthias W., Koti, M, Kraft, P, Kupryjanczyk, J, Lambrechts, D, Larson, MC, Le Marchand, L, Lele, S, Lester, J, Li, AJ, Liang, D, Berchuck, Andrew, Liebrich, C, Lipworth, L, Lissowska, J, Lu, L, Lu, KH, Macciotta, A, Mattiello, A, May, T, McAlpine, JN, McGuire, V
المساهمون: The University of Newcastle. College of Health, Medicine & Wellbeing, School of Biomedical Sciences and Pharmacy
بيانات النشر: American Association for Cancer Research
سنة النشر: 2021
المجموعة: NOVA: The University of Newcastle Research Online (Australia)
مصطلحات موضوعية: cancer, female, endometrial cancer, ovarian cancer, SDG 3, Sustainable Development Goals
الوصف: 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.
نوع الوثيقة: article in journal/newspaper
اللغة: English
تدمد: 1055-9965
العلاقة: Cancer Epidemiology, Biomarkers & Prevention Vol. 30, Issue 1, p. 217-228; http://hdl.handle.net/1959.13/1465520Test; uon:47283
الإتاحة: http://hdl.handle.net/1959.13/1465520Test
رقم الانضمام: edsbas.88AB4F07
قاعدة البيانات: BASE