open access publication

Article, 2024

Genome-wide association analyses of ovarian cancer patients undergoing primary debulking surgery identify candidate genes for residual disease

NPJ GENOMIC MEDICINE, ISSN 2056-7944, 2056-7944, Volume 9, 1, 10.1038/s41525-024-00395-y

Contributors

Ramachandran, Dhanya 0000-0001-8139-7799 Tyrer, Jonathan P. [1] Kommoss, Stefan [2] [3] [4] DeFazio, Anna 0000-0003-0057-4744 [5] [6] [7] [8] Riggan, Marjorie J. [9] Webb, Penelope 0000-0003-0733-5930 [10] Fasching, Peter A. [11] Lambrechts, Diether 0000-0002-3429-302X [12] [13] Garcia, Maria J. [14] Rodriguez-Antona, Cristina [15] [16] [17] [18] Goodman, Marc T. [19] Modugno, Francesmary [20] [21] [22] Moysich, Kirsten B. [23] Karlan, Beth Y. [24] [25] [26] [27] Lester, Jenny [24] [25] [26] [27] Kjaer, Susanne K. [28] [29] [30] Jensen, Allan 0000-0003-1103-2860 [28] Hogdall, Estrid [29] [31] Goode, Ellen L. [32] Cliby, William A. [33] Kumar, Amanika [33] Wang, Chen [32] Cunningham, Julie M. [32] Winham, Stacey J. [32] Monteiro, Alvaro N. [34] Schildkraut, Joellen M. [35] [36] Cramer, Daniel W. 0000-0002-8024-3066 [37] [38] [39] [40] Terry, Kathryn L. [37] [38] [39] [40] Titus, Linda [41] Bjorge, L. [42] [43] Thomsen, Liv Cecilie Vestrheim [42] [43] Pejovic, Tanja [44] [45] Hogdall, Claus K. [29] [30] McNeish, Iain A. [46] [47] May, Taymaa [48] [49] [50] Huntsman, David G. [51] [52] Pfisterer, J. [53] Canzler, U. [54] [55] [56] [57] [58] Park-Simon, T. W. 0000-0002-2863-3040 [59] Schroeder, W. [60] [61] Belau, A. [62] [63] Hanker, Lars [64] [65] [66] [67] Harter, Philipp [68] Sehouli, Jalid 0000-0002-5963-6623 [69] [70] [71] Kimmig, Rainer [72] De Gregorio, N. [73] [74] Schmalfeldt, Barbara [75] [76] Baumann, K. [77] [78] Hilpert, Felix [66] [67] [79] Burges, A. [80] Winterhoff, B. [81] [82] Schuermann, Peter [59] Speith, Lisa-Marie [59] Hillemanns, Peter [59] Berchuck, Andrew [9] Johnatty, Sharon E. 0000-0002-7888-1966 [10] Ramus, Susan J. [83] [84] Chenevix-Trench, Georgia [10] Pharoah, P. P. D. [1] [19] Doerk, Thilo (Corresponding author) [59] Heitz, Florian (Corresponding author) [68] [69] [70] [71] [85] AOCS Grp OPAL Study Grp

Affiliations

  1. [1] Univ Cambridge, Dept Oncol, Ctr Canc Genet Epidemiol, Cambridge, England
    2. [NORA names: United Kingdom; Europe, Non-EU; OECD];
  2. [2] Tuebingen Univ Hosp, Dept Womens Hlth, Tubingen, Germany
    3. [NORA names: Germany; Europe, EU; OECD];
  3. [3] Tuebingen Univ Hosp, Dept Womens Hlth, Tubingen, Germany
    4. [NORA names: Germany; Europe, EU; OECD];
  4. [4] Tuebingen Univ Hosp, Dept Womens Hlth, Tubingen, Germany
    5. [NORA names: Germany; Europe, EU; OECD];
  5. [5] Westmead Hosp, Dept Gynaecol Oncol, Sydney, NSW, Australia
    6. [NORA names: Australia; Oceania; OECD];

Abstract

Survival from ovarian cancer depends on the resection status after primary surgery. We performed genome-wide association analyses for resection status of 7705 ovarian cancer patients, including 4954 with high-grade serous carcinoma (HGSOC), to identify variants associated with residual disease. The most significant association with resection status was observed for rs72845444, upstream of MGMT, in HGSOC (p = 3.9 x 10(-8)). In gene-based analyses, PPP2R5C was the most strongly associated gene in HGSOC after stage adjustment. In an independent set of 378 ovarian tumours from the AGO-OVAR 11 study, variants near MGMT and PPP2R5C correlated with methylation and transcript levels, and PPP2R5C mRNA levels predicted progression-free survival in patients with residual disease. MGMT encodes a DNA repair enzyme, and PPP2R5C encodes the B56. subunit of the PP2A tumour suppressor. Our results link heritable variation at these two loci with resection status in HGSOC.

Data Provider: Clarivate

LINKS
-

Matching Records in NORA

SUBJECTS
+

METRICS
+