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

被引：1

作者：

Ramachandran, Dhanya

Tyrer, Jonathan P. ^{[2
]}

Kommoss, Stefan ^{[3
]}

DeFazio, Anna ^{[4
,5
,6
,7
]}

Riggan, Marjorie J. ^{[8
]}

Webb, PenelopeM. ^{[9
]}

Fasching, Peter A. ^{[10
]}

Lambrechts, Diether ^{[11
,12
]}

Garcia, Maria J. ^{[13
]}

Rodriguez-Antona, Cristina ^{[14
,15
]}

Goodman, Marc T. ^{[16
]}

Modugno, Francesmary ^{[17
,18
,19
]}

Moysich, Kirsten B. ^{[20
]}

Karlan, Beth Y. ^{[21
]}

Lester, Jenny ^{[21
]}

Kjaer, Susanne K. ^{[22
,23
]}

Jensen, Allan ^{[22
]}

Hogdall, Estrid ^{[24
]}

Goode, Ellen L. ^{[25
]}

Cliby, William A. ^{[26
]}

Kumar, Amanika ^{[26
]}

Wang, Chen ^{[27
]}

Cunningham, Julie M. ^{[28
]}

Winham, Stacey J. ^{[27
]}

Monteiro, Alvaro N. ^{[29
]}

Schildkraut, Joellen M. ^{[30
]}

Cramer, Daniel W. ^{[31
,32
,33
]}

Terry, Kathryn L. ^{[31
,32
,33
]}

Titus, Linda ^{[34
]}

Bjorge, Line ^{[35
,36
]}

Thomsen, Liv Cecilie Vestrheim ^{[35
,36
]}

Pejovic, Tanja ^{[38
,39
]}

Hogdall, Claus K. ^{[23
]}

McNeish, Iain A. ^{[40
,41
,42
]}

May, Taymaa ^{[43
]}

Huntsman, David G. ^{[44
,45
]}

Pfisterer, Jacobus ^{[46
]}

Canzler, Ulrich ^{[47
,48
]}

Park-Simon, Tjoung-Won ^{[1
]}

Schroeder, Willibald ^{[49
,50
]}

Belau, Antje ^{[51
,52
]}

Hanker, Lars ^{[53
,54
]}

Harter, Philipp ^{[55
]}

Sehouli, Jalid ^{[56
]}

Kimmig, Rainer ^{[57
]}

de Gregorio, Nikolaus ^{[58
,59
]}

Schmalfeldt, Barbara ^{[60
]}

Baumann, Klaus ^{[61
,62
]}

Hilpert, Felix ^{[63
,64
]}

Burges, Alexander ^{[65
]}

机构：

[1] Hannover Med Sch, Gynaecol Res Unit, Hannover, Germany

[2] Univ Cambridge, Dept Oncol, Ctr Canc Genet Epidemiol, Cambridge, England

[3] Tuebingen Univ Hosp, Dept Womens Hlth, Tubingen, Germany

[4] Univ Sydney, Westmead Inst Med Res, Ctr Canc Res, Sydney, NSW, Australia

[5] Univ Sydney, Discipline Obstet & Gynaecol, Sydney, NSW, Australia

[6] Westmead Hosp, Dept Gynaecol Oncol, Sydney, NSW, Australia

[7] Univ Sydney, Joint Venture Canc Council NSW, Daffodil Ctr, Sydney, NSW, Australia

[8] Duke Univ, Div Gynecol Oncol, Dept Obstet & Gynecol, Med Ctr, Durham, NC USA

[9] QIMR Berghofer Med Res Inst, Populat Hlth Program, Brisbane, Qld, Australia

[10] Friedrich Alexander Univ Erlangen Nuremberg, Univ Hosp Erlangen, Dept Gynecol & Obstet, Comprehens Canc Ctr Erlangen EMN, Erlangen, Germany

[11] Katholieke Univ Leuven, Dept Human Genet, Lab Translat Genet, Leuven, Belgium

[12] VIB, VIB Ctr Canc Biol, Leuven, Belgium

[13] Rey Juan Carlos Univ, Dept Basic Hlth Sci, Biochem & Mol Biol Area, Fac Hlth Sci, Madrid, Spain

[14] Spanish Natl Canc Res Ctr CNIO, Hereditary Endocrine Canc Grp, Madrid, Spain

[15] Inst Salud Carlos III, Ctr Biomed Network Res Rare Dis CIBERER, Madrid, Spain

[16] Cedars Sinai Med Ctr, Canc Prevent & Control Program, Cedars Sinai Canc, Los Angeles, CA USA

[17] Univ Pittsburgh, Dept Epidemiol, Sch Publ Hlth, Pittsburgh, PA USA

[18] Univ Pittsburgh, Dept Obstet Gynecol & Reproduct Sci, Div Gynecol Oncol, Sch Med, Pittsburgh, PA USA

[19] Magee WomensResearch Inst, Womens Canc Res Ctr, Pittsburgh, PA USA

[20] Roswell Park Canc Inst, Dept Canc Prevent & Control, Buffalo, NY USA

[21] Univ Calif LosAngeles, David Geffen Sch Med, Dept Obstet & Gynecol, Los Angeles, CA USA

[22] Danish Canc Inst, Dept Virus Lifestyle & Genes, Copenhagen, Denmark

[23] Univ Copenhagen, Dept Gynaecol, Rigshosp, Copenhagen, Denmark

[24] Univ Copenhagen, Herlev Hosp, Dept Pathol, Copenhagen, Denmark

[25] Mayo Clin, Div Epidemiol, Dept Quantitat Hlth Sci, Rochester, MN USA

[26] MayoClin, Div Gynecol Oncol, Dept Obstet & Gynecol, Rochester, MN USA

[27] Mayo Clin, Div Computat Biol, Dept Quantitat Hlth Sci, Rochester, MN USA

[28] Mayo Clin, Dept Lab Med & Pathol, Rochester, MN USA

[29] H Lee Moffitt Canc Ctr & Res Inst, Dept Canc Epidemiol, Tampa, FL USA

[30] Emory Univ, Rollins Sch Publ Hlth, Dept Epidemiol, Atlanta, GA USA

[31] Brigham & Womens Hosp, Dept Obstet & Gynecl, Obstet & Gynecol Epidemiol Ctr, Boston, MA USA

[32] Harvard Med Sch, Boston, MA USA

[33] Harvard T H Chan Sch Publ Hlth, Dept Epidemiol, Boston, MA USA

[34] Norris Cotton Canc Ctr, Lebanon, NH USA

[35] Haukeland Hosp, Dept Obstet & Gynecol, Bergen, Norway

[36] Univ Bergen, Dept Clin Sci, Ctr Canc Biomarkers CCBIO, Bergen, Norway

[37] Univ NSWSydney, Sch Clin Med, UNSW Med & Hlth, Sydney, NSW, Australia

[38] Providence Med Ctr, Dept ObGyn, Medford, OR USA

[39] Oregon Hlth & Sci Univ, Knight Canc Inst, Portland, OR USA

[40] Imperial Coll London, Dept Surg Canc, Div Canc, London, England

[41] Imperial Coll London, Dept Surg Canc, Ovarian Canc Act Res Ctr, London, England

[42] Univ Glasgow, Inst Canc Sci, Glasgow, Lanark, Scotland

[43] Univ Hlth Network, Princess Margaret Hosp, Div Gynecol Oncol, Toronto, ON, Canada

[44] Univ British Columbia, Dept Obstet & Gynecol, Vancouver, BC, Canada

[45] BC Canc Res Ctr, Dept Mol Oncol, Vancouver, BC, Canada

[46] Gynecol Oncol Ctr, Kiel, Germany

[47] Tech Univ Dresden, Univ Hosp Carl Gustav Carus, Dresden, Germany

[48] Partner Site Dresden, Natl Ctr Tumor Dis NCT, Dresden, Germany

[49] Klinikum Bremen Mitte, Bremen, Germany

[50] Gynaekologicum Bremen, Bremen, Germany

来源：

NPJ GENOMIC MEDICINE | 2024年 / 9卷 / 01期

基金：

英国惠康基金; 美国国家卫生研究院; 加拿大健康研究院; 英国医学研究理事会;

关键词：

SUBOPTIMAL CYTOREDUCTION; DRUG-RESISTANCE; SURVIVAL; BEVACIZUMAB; DIAGNOSIS; TRIAL;

D O I：

10.1038/s41525-024-00395-y

中图分类号：

Q3 [遗传学];

学科分类号：

071007 ; 090102 ;

摘要：

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.

引用

页数：12

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