Genome-wide association analyses of ovarian cancer patients undergoing primary debulking surgery identify candidate genes for residual disease.
Dhanya RamachandranJonathan P TyrerStefan KommossAnna DeFazioMarjorie J Riggannull nullPenelope M WebbPeter A FaschingDiether LambrechtsMaría J GarcíaCristina Rodríguez-AntonaMarc T GoodmanFrancesmary ModugnoKirsten B MoysichBeth Y KarlanJenny LesterSusanne K KjaerAllan JensenEstrid HøgdallEllen L GoodeWilliam A ClibyAmanika KumarChen WangJulie M CunninghamStacey J WinhamAlvaro N A MonteiroJoellen M SchildkrautDaniel W CramerKathryn L TerryLinda TitusLine BjorgeLiv Cecilie Vestrheim Thomsennull nullTanja PejovicClaus K HøgdallIain A McNeishTaymaa MayDavid G HuntsmanJacobus PfistererUlrich CanzlerTjoung-Won Park-SimonWillibald SchröderAntje BelauLars HankerPhilipp HarterJalid SehouliRainer KimmigNikolaus de GregorioBarbara SchmalfeldtKlaus BaumannFelix HilpertAlexander BurgesBoris WinterhoffPeter SchürmannLisa-Marie SpeithPeter HillemannsAndrew BerchuckSharon E JohnattySusan J RamusGeorgia Chenevix-TrenchPaul David Peter PharoahThilo DörkFlorian HeitzPublished in: NPJ genomic medicine (2024)
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 × 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 B56γ subunit of the PP2A tumour suppressor. Our results link heritable variation at these two loci with resection status in HGSOC.
Keyphrases
- genome wide association
- high grade
- dna repair
- free survival
- copy number
- genome wide
- minimally invasive
- patients undergoing
- coronary artery bypass
- dna damage
- low grade
- dna methylation
- radiation therapy
- surgical site infection
- coronary artery disease
- atrial fibrillation
- dna damage response
- transcription factor
- genome wide association study