Bjorge, Line
Mayo Clinic
Department of Obstetrics and Gynecology, Haukeland University Hospital, 5021 Bergen, Norway.
Citations 2
CA-125 Levels Are Predictive of Survival in Low-Grade Serous Ovarian Cancer—A Multicenter Analysis
Wohlmuth, Christoph , Djedovic, Vladimir, Kjær, Susanne K. , DeFazio, Anna , Johnatty, Sharon E. , Webb, Penelope M. , Lambrechts, Diether , Schildkraut, Joellen M. , Thomsen, Liv Cecilie Vestrheim , Bjørge, Line , Høgdall, Estrid , Høgdall, Claus , Goode, Ellen L. , Matsuo, Keitaro , Karlan, Beth Y. , Lester, Jenny, Goodman, Marc T. , Thompson, Pamela J., Riggan, Marjorie J. , Lajkosz, Katherine , Tone, Alicia , May, Taymaa, Lambrechts, Diether , Fazio, Anna de , Webb, Penelope M , Thomsen, Liv Cecilie Vestrheim , Bjorge, Line , Høgdall, Estrid , Høgdall, Claus K , Matsuo, Keitaro , Karlan, Beth Y , Tone, Alicia , Lambrechts, Diether , Kjaer, Susanne K , Lambrechts, Diether , Goodman, Marc T , Jensen, Allan , Glasspool, Rosalind , Roxburgh, Patricia , Modugno, Francesmary , Berchuck, Andrew , Winham, Stacey J. , Pejovic, Tanja B.
Cancers | April 13, 2022 | Volume: 14 | Issue: 8 | Pages: 1954
Objective: Studies on low-grade serous ovarian cancer (LGSC) are limited by a low number of cases. The aim of this study was to define the prognostic significance of age, stage, and CA-125 levels on survival in a multi-institutional cohort of women with pathologically confirmed LGSC. Methods: Women with LGSC were identified from the collaborative Ovarian Cancer Association Consortium (OCAC). Cases of newly diagnosed primary LGSC were included if peri-operative CA-125 levels were available. Age at diagnosis, FIGO stage, pre- and post-treatment CA-125 levels, residual disease, adjuvant chemotherapy, disease recurrence, and vital status were collected by the participating institutions. Progression-free (PFS) and overall survival (OS) were calculated. Multivariable (MVA) Cox proportional hazard models were used and hazard ratios (HR) calculated. Results: A total of 176 women with LGSC were included in this study; 82% had stage III/IV disease. The median PFS was 2.3 years and the median OS was 6.4 years. Age at diagnosis was not significantly associated with worse PFS (p = 0.23) or OS (p = 0.3) (HR per year: 0.99; 95%CI, 0.96–1.01 and 0.98; 95%CI 0.95–1.01). FIGO stage III/IV was independently associated with PFS (HR 4.26, 95%CI 1.43–12.73) and OS (HR 1.69, 95%CI 0.56–5.05). Elevated CA-125 (≥35 U/mL) at diagnosis was not significantly associated with worse PFS (p = 0.87) or OS (p = 0.78) in MVA. Elevated CA-125 (≥35 U/mL) after completion of primary treatment was independently associated with worse PFS (HR 2.81, 95%CI 1.36–5.81) and OS (HR 6.62, 95%CI 2.45–17.92). In the MVA, residual disease was independently associated with PFS (0.022), but not OS (0.85). Conclusion: Advanced LGSC was associated with poor long-term prognosis. FIGO stage and abnormal post-treatment CA-125 level are key prognostic factors inversely associated with PFS and OS. Highlights: 1. Through a multi-center collaborative effort, data from 176 women with low-grade serous ovarian cancer were analyzed. 2. Although low-grade serous ovarian cancer is often considered indolent, the progression-free and overall survival are poor. 3. Elevated post-treatment CA-125 levels are independently associated with poor survival.
rs495139 in the TYMS-ENOSF1 Region and Risk of Ovarian Carcinoma of Mucinous Histology
Kelemen, Linda E. , Earp, Madalene A. , Chenevix‐Trench, Georgia , Group, On behalf of Australian Ovarian Cancer Study, Fasching, Peter A. , Beckmann, Matthias W. , Ekici, Arif B. , Hein, Alexander , Lambrechts, Diether , Lambrechts, Sandrina, Nieuwenhuysen, Els Van , Vergote, Ignace , Rossing, Mary Anne, Chang‐Claude, Jenny , Moysich, Kirsten, Cannioto, Rikki , Lele, Shashikant , Odunsi, Kunle , Goodman, Marc T. , Shvetsov, Yurii B. , Thompson, Pamela J., Dörk, Thilo , Antonenkova, Natalia, Bogdanova, Natalia , Hillemanns, Peter , Runnebaum, Ingo B. , Harter, Philipp , Heitz, Florian , Schwaab, Ira, Edwards, Robert P., Kelley, Joseph L., Ness, Roberta B., Lester, Jenny, Oršulić, Sandra , Walsh, Christine M. , Jensen, Allan , Cunningham, Julie M. , Vierkant, Robert A. , Bruinsma, Fiona , Hildebrandt, Michelle, Liang, Dong , Lu, Karen H., Wu, Xifeng , Sellers, Thomas A. , Schildkraut, Joellen M. , Iversen, Edwin S., Terry, Kathryn L. , Tworoger, Shelley S. , Thomsen, Liv Vestrheim, Krakstad, Camilla , Tangen, Ingvild L. , Aben, Katja K.H. , Massuger, Leon F.A.G. , Altena, Anne M. van , Bean, Yukie T., Kellar, Melissa, Le, Nhu D. , Brooks‐Wilson, Angela , Jakubowska, Anna , Lubiński, Jan , Wentzensen, Nicolas , Brinton, Louise A. , Lissowska, Jolanta , Høgdall, Estrid , Engelholm, Svend Aage, Høgdall, Claus , Lundvall, Lene, Nedergaard, Lotte , Dicks, Ed , Song, Honglin , McNeish, Iain A. , Carty, Karen , Eccles, Diana , Whittemore, Alice S. , McGuire, Valerie , Rothstein, Joseph H. , Sieh, Weiva , Narod, Steven A., Phelan, Catherine, McLaughlin, John, Ziogas, Argyrios, Menon, Usha , Gayther, Simon A. , Ramus, Susan J. , Wu, Anna H. , Pearce, Celeste Leigh, Lee, Alice W. , Pike, Malcolm C. , Kupryjańczyk, Jolanta , Podgórska, Agnieszka , Plisiecka-Hałasa, Joanna, Sawicki, Włodzimierz , Goode, Ellen L. , Berchuck, Andrew, Lu, Karen H. , Lambrechts, Diether , Earp, Madalene, Hein, Alexander , Behrens, Sabine , Hillemanns, Peter , Nevanlinna, H , Kjaer, Susanne K , Jensen, Allan , Cunningham, Julie M , Vierkant, Robert A , Bjorge, Line , Gronwald, Jacek , Brinton, Louise A , Pharoah, Paul D P , Tyrer, Jonathan P. , McNeish, Iain A , Eccles, Diana , Menon, Usha , Ramus, Susan J , Dörk, Thilo , Lambrechts, Diether , Tworoger, Shelley S , Moysich, Kirsten , Lissowska, Jolanta , Brooks-Wilson, Angela R , Heitz, Florian , Jakubowska, Anna , Kupryjanczyk, Jolanta , Lambrechts, Diether , Sieh, Weiva , Ekici, Arif B , Bogdanova, Natalia V , Chenevix-Trench, Georgia , Høgdall, Estrid , Høgdall, Claus K , Lubinski, Jan , Goodman, Marc T , Fridley, Brooke L. , Group, On behalf of Australian Ovarian Cancer Study, Doherty, Jennifer A. , Behrens, Sabine , Moysich, Kirsten B. , Wilkens, Lynne R. , Bois, Andreas du , Bützow, Ralf C. , Pelttari, Liisa M. , Nevanlinna, Heli , Modugno, Francesmary , Karlan, Beth Y. , Walsh, Christine, Kjær, Susanne K. , Giles, Graham G. , Southey, Melissa C. , Levine, Douglas A. , Cramer, Daniel W. , Poole, Elizabeth M. , Bandera, Elisa V. , Olson, Sara H. , Orlow, Irene , Thomsen, Liv Cecilie Vestrheim , Bjørge, Line , Kiemeney, Lambertus A. , Pejovic, Tanja B. , Cook, Linda S. , Gronwald, Jacek , Cybulski, Cezary , Pharoah, Paul D.P. , Siddiqui, Nadeem , Glasspool, Rosalind , Paul, James , Campbell, Ian , McLaughlin, John, Risch, Harvey A. , Anton‐Culver, Hoda , Gentry‐Maharaj, Aleksandra
International Journal of Molecular Sciences | August 21, 2018 | Volume: 19 | Issue: 9 | Pages: 2473
Thymidylate synthase (TYMS) is a crucial enzyme for DNA synthesis. TYMS expression is regulated by its antisense mRNA, ENOSF1. Disrupted regulation may promote uncontrolled DNA synthesis and tumor growth. We sought to replicate our previously reported association between rs495139 in the TYMS-ENOSF1 3′ gene region and increased risk of mucinous ovarian carcinoma (MOC) in an independent sample. Genotypes from 24,351 controls to 15,000 women with invasive OC, including 665 MOC, were available. We estimated per-allele odds ratios (OR) and 95% confidence intervals (CI) using unconditional logistic regression, and meta-analysis when combining these data with our previous report. The association between rs495139 and MOC was not significant in the independent sample (OR = 1.09; 95% CI = 0.97–1.22; p = 0.15; N = 665 cases). Meta-analysis suggested a weak association (OR = 1.13; 95% CI = 1.03–1.24; p = 0.01; N = 1019 cases). No significant association with risk of other OC histologic types was observed (p = 0.05 for tumor heterogeneity). In expression quantitative trait locus (eQTL) analysis, the rs495139 allele was positively associated with ENOSF1 mRNA expression in normal tissues of the gastrointestinal system, particularly esophageal mucosa (r = 0.51, p = 1.7 × 10−28), and nonsignificantly in five MOC tumors. The association results, along with inconclusive tumor eQTL findings, suggest that a true effect of rs495139 might be small.