1,126 results on '"Harris, Holly"'
Search Results
2. Advanced Health Information Technologies to Engage Parents, Clinicians, and Community Nutritionists in Coordinating Responsive Parenting Care: Descriptive Case Series of the Women, Infants, and Children Enhancements to Early Healthy Lifestyles for Baby (WEE Baby) Care Randomized Controlled Trial
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Kling, Samantha MR, Harris, Holly A, Marini, Michele, Cook, Adam, Hess, Lindsey B, Lutcher, Shawnee, Mowery, Jacob, Bell, Scott, Hassink, Sandra, Hayward, Shannon B, Johnson, Greg, Franceschelli Hosterman, Jennifer, Paul, Ian M, Seiler, Christopher, Sword, Shirley, Savage, Jennifer S, and Bailey-Davis, Lisa
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Pediatrics ,RJ1-570 - Abstract
BackgroundSocioeconomically disadvantaged newborns receive care from primary care providers (PCPs) and Women, Infants, and Children (WIC) nutritionists. However, care is not coordinated between these settings, which can result in conflicting messages. Stakeholders support an integrated approach that coordinates services between settings with care tailored to patient-centered needs. ObjectiveThis analysis describes the usability of advanced health information technologies aiming to engage parents in self-reporting parenting practices, integrate data into electronic health records to inform and facilitate documentation of provided responsive parenting (RP) care, and share data between settings to create opportunities to coordinate care between PCPs and WIC nutritionists. MethodsParents and newborns (dyads) who were eligible for WIC care and received pediatric care in a single health system were recruited and randomized to a RP intervention or control group. For the 6-month intervention, electronic systems were created to facilitate documentation, data sharing, and coordination of provided RP care. Prior to PCP visits, parents were prompted to respond to the Early Healthy Lifestyles (EHL) self-assessment tool to capture current RP practices. Responses were integrated into the electronic health record and shared with WIC. Documentation of RP care and an 80-character, free-text comment were shared between WIC and PCPs. A care coordination opportunity existed when the dyad attended a WIC visit and these data were available from the PCP, and vice versa. Care coordination was demonstrated when WIC or PCPs interacted with data and documented RP care provided at the visit. ResultsDyads (N=131) attended 459 PCP (3.5, SD 1.0 per dyad) and 296 WIC (2.3, SD 1.0 per dyad) visits. Parents completed the EHL tool prior to 53.2% (244/459) of PCP visits (1.9, SD 1.2 per dyad), PCPs documented provided RP care at 35.3% (162/459) of visits, and data were shared with WIC following 100% (459/459) of PCP visits. A WIC visit followed a PCP visit 50.3% (231/459) of the time; thus, there were 1.8 (SD 0.8 per dyad) PCP to WIC care coordination opportunities. WIC coordinated care by documenting RP care at 66.7% (154/231) of opportunities (1.2, SD 0.9 per dyad). WIC visits were followed by a PCP visit 58.9% (116/197) of the time; thus, there were 0.9 (SD 0.8 per dyad) WIC to PCP care coordination opportunities. PCPs coordinated care by documenting RP care at 44.0% (51/116) of opportunities (0.4, SD 0.6 per dyad). ConclusionsResults support the usability of advanced health information technology strategies to collect patient-reported data and share these data between multiple providers. Although PCPs and WIC shared data, WIC nutritionists were more likely to use data and document RP care to coordinate care than PCPs. Variability in timing, sequence, and frequency of visits underscores the need for flexibility in pragmatic studies. Trial RegistrationClinicalTrials.gov NCT03482908; https://clinicaltrials.gov/ct2/show/NCT03482908 International Registered Report Identifier (IRRID)RR2-10.1186/s12887-018-1263-z
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- 2020
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3. The Impact of Cognitive Behavioral Therapy on Sleep Problems in Autistic Children with Co-occurring Anxiety
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Harris, Holly K., Kook, Minjee, Boedeker, Peter, Gusick, Andrew G., Lyons-Warren, Ariel M., Goin-Kochel, Robin P., Murali, Chaya, Berry, Leandra N., and Storch, Eric A.
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- 2024
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4. Male and Female Toddlers with DSM-5 Autism Spectrum Disorder have Similar Developmental Profiles and Core Autism Symptoms
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Harris, Holly K., Sideridis, Georgios D., Barbaresi, William J., and Harstad, Elizabeth
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- 2024
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5. A framework for assessing interactions for risk stratification models: the example of ovarian cancer
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Phung, Minh Tung, Lee, Alice W, McLean, Karen, Anton-Culver, Hoda, Bandera, Elisa V, Carney, Michael E, Chang-Claude, Jenny, Cramer, Daniel W, Doherty, Jennifer Anne, Fortner, Renee T, Goodman, Marc T, Harris, Holly R, Jensen, Allan, Modugno, Francesmary, Moysich, Kirsten B, Pharoah, Paul DP, Qin, Bo, Terry, Kathryn L, Titus, Linda J, Webb, Penelope M, Wu, Anna H, Zeinomar, Nur, Ziogas, Argyrios, Berchuck, Andrew, Cho, Kathleen R, Hanley, Gillian E, Meza, Rafael, Mukherjee, Bhramar, Pike, Malcolm C, Pearce, Celeste Leigh, and Trabert, Britton
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Biomedical and Clinical Sciences ,Oncology and Carcinogenesis ,Rare Diseases ,Women's Health ,Ovarian Cancer ,Cancer ,Prevention ,Aetiology ,2.1 Biological and endogenous factors ,2.5 Research design and methodologies (aetiology) ,Good Health and Well Being ,Humans ,Female ,Ovarian Neoplasms ,Risk Factors ,Risk Assessment ,Case-Control Studies ,Oncology & Carcinogenesis ,Oncology and carcinogenesis - Abstract
Generally, risk stratification models for cancer use effect estimates from risk/protective factor analyses that have not assessed potential interactions between these exposures. We have developed a 4-criterion framework for assessing interactions that includes statistical, qualitative, biological, and practical approaches. We present the application of this framework in an ovarian cancer setting because this is an important step in developing more accurate risk stratification models. Using data from 9 case-control studies in the Ovarian Cancer Association Consortium, we conducted a comprehensive analysis of interactions among 15 unequivocal risk and protective factors for ovarian cancer (including 14 non-genetic factors and a 36-variant polygenic score) with age and menopausal status. Pairwise interactions between the risk/protective factors were also assessed. We found that menopausal status modifies the association among endometriosis, first-degree family history of ovarian cancer, breastfeeding, and depot-medroxyprogesterone acetate use and disease risk, highlighting the importance of understanding multiplicative interactions when developing risk prediction models.
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- 2023
6. “My words matter”: perspectives on evaluation from people who access and work in recovery colleges
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Soklaridis, Sophie, Shier, Rowen, Black, Georgia, Bellissimo, Gail, Di Giandomenico, Anna, Gruszecki, Sam, Lin, Elizabeth, Rovet, Jordana, and Harris, Holly
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- 2024
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7. Experience Foraging: Connecting with Nature and Each Other Through Foraging Field Courses in Kent, England
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Harris, Holly, Dhyani, Shalini, editor, and Sardeshpande, Mallika, editor
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- 2024
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8. Latent Class Analysis Identifies Distinctive Behavioral Subtypes in Children with Fragile X Syndrome
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Kaufmann, Walter E., Raspa, Melissa, Bann, Carla M., Gable, Julia M., Harris, Holly K., Budimirovic, Dejan B., and Lozano, Reymundo
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- 2024
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9. Menopausal hormone therapy use and risk of ovarian cancer by race: the ovarian cancer in women of African ancestry consortium
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Petrick, Jessica L., Joslin, Charlotte E., Johnson, Courtney E., Camacho, T. Fabian, Peres, Lauren C., Bandera, Elisa V., Barnard, Mollie E., Beeghly, Alicia, Bethea, Traci N., Dempsey, Lauren F., Guertin, Kristin, Harris, Holly R., Moorman, Patricia G., Myers, Evan R., Ochs-Balcom, Heather M., Rosenow, Will, Setiawan, V. Wendy, Wu, Anna H., Schildkraut, Joellen M., and Rosenberg, Lynn
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- 2023
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10. Lifetime ovulatory years and risk of epithelial ovarian cancer: a multinational pooled analysis
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Fu, Zhuxuan, Brooks, Maria Mori, Irvin, Sarah, Jordan, Susan, Aben, Katja KH, Anton-Culver, Hoda, Bandera, Elisa V, Beckmann, Matthias W, Berchuck, Andrew, Brooks-Wilson, Angela, Chang-Claude, Jenny, Cook, Linda S, Cramer, Daniel W, Cushing-Haugen, Kara L, Doherty, Jennifer A, Ekici, Arif B, Fasching, Peter A, Fortner, Renée T, Gayther, Simon A, Gentry-Maharaj, Aleksandra, Giles, Graham G, Goode, Ellen L, Goodman, Marc T, Group, AOCS, Harris, Holly R, Hein, Alexander, Kaaks, Rudolf, Kiemeney, Lambertus A, Köbel, Martin, Kotsopoulos, Joanne, Le, Nhu D, Lee, Alice W, Matsuo, Keitaro, McGuire, Valerie, McLaughlin, John R, Menon, Usha, Milne, Roger L, Moysich, Kirsten B, Pearce, Celeste Leigh, Pike, Malcolm C, Qin, Bo, Ramus, Susan J, Riggan, Marjorie J, Rothstein, Joseph H, Schildkraut, Joellen M, Sieh, Weiva, Sutphen, Rebecca, Terry, Kathryn L, Thompson, Pamela J, Titus, Linda, van Altena, Anne M, White, Emily, Whittemore, Alice S, Wu, Anna H, Zheng, Wei, Ziogas, Argyrios, Taylor, Sarah E, Tang, Lu, Songer, Thomas, Wentzensen, Nicolas, Webb, Penelope M, Risch, Harvey A, and Modugno, Francesmary
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Biomedical and Clinical Sciences ,Oncology and Carcinogenesis ,Rare Diseases ,Clinical Research ,Cancer ,Ovarian Cancer ,Prevention ,Pregnancy ,Humans ,Female ,Carcinoma ,Ovarian Epithelial ,Ovarian Neoplasms ,Risk Factors ,Parity ,Contraceptives ,Oral ,Case-Control Studies ,AOCS Group ,Oncology & Carcinogenesis ,Oncology and carcinogenesis - Abstract
BackgroundThe role of ovulation in epithelial ovarian cancer (EOC) is supported by the consistent protective effects of parity and oral contraceptive use. Whether these factors protect through anovulation alone remains unclear. We explored the association between lifetime ovulatory years (LOY) and EOC.MethodsLOY was calculated using 12 algorithms. Odds ratios (ORs) and 95% confidence intervals (CIs) estimated the association between LOY or LOY components and EOC among 26 204 control participants and 21 267 case patients from 25 studies. To assess whether LOY components act through ovulation suppression alone, we compared beta coefficients obtained from regression models with expected estimates assuming 1 year of ovulation suppression has the same effect regardless of source.ResultsLOY was associated with increased EOC risk (OR per year increase = 1.014, 95% CI = 1.009 to 1.020 to OR per year increase = 1.044, 95% CI = 1.041 to 1.048). Individual LOY components, except age at menarche, also associated with EOC. The estimated model coefficient for oral contraceptive use and pregnancies were 4.45 times and 12- to 15-fold greater than expected, respectively. LOY was associated with high-grade serous, low-grade serous, endometrioid, and clear cell histotypes (ORs per year increase = 1.054, 1.040, 1.065, and 1.098, respectively) but not mucinous tumors. Estimated coefficients of LOY components were close to expected estimates for high-grade serous but larger than expected for low-grade serous, endometrioid, and clear cell histotypes.ConclusionsLOY is positively associated with nonmucinous EOC. Differences between estimated and expected model coefficients for LOY components suggest factors beyond ovulation underlie the associations between LOY components and EOC in general and for non-HGSOC.
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- 2023
11. p53 and ovarian carcinoma survival: an Ovarian Tumor Tissue Analysis consortium study
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Köbel, Martin, Kang, Eun‐Young, Weir, Ashley, Rambau, Peter F, Lee, Cheng‐Han, Nelson, Gregg S, Ghatage, Prafull, Meagher, Nicola S, Riggan, Marjorie J, Alsop, Jennifer, Anglesio, Michael S, Beckmann, Matthias W, Bisinotto, Christiani, Boisen, Michelle, Boros, Jessica, Brand, Alison H, Brooks‐Wilson, Angela, Carney, Michael E, Coulson, Penny, Courtney‐Brooks, Madeleine, Cushing‐Haugen, Kara L, Cybulski, Cezary, Deen, Suha, El‐Bahrawy, Mona A, Elishaev, Esther, Erber, Ramona, Fereday, Sian, Group, AOCS, Fischer, Anna, Gayther, Simon A, Barquin‐Garcia, Arantzazu, Gentry‐Maharaj, Aleksandra, Gilks, C Blake, Gronwald, Helena, Grube, Marcel, Harnett, Paul R, Harris, Holly R, Hartkopf, Andreas D, Hartmann, Arndt, Hein, Alexander, Hendley, Joy, Hernandez, Brenda Y, Huang, Yajue, Jakubowska, Anna, Jimenez‐Linan, Mercedes, Jones, Michael E, Kennedy, Catherine J, Kluz, Tomasz, Koziak, Jennifer M, Lesnock, Jaime, Lester, Jenny, Lubiński, Jan, Longacre, Teri A, Lycke, Maria, Mateoiu, Constantina, McCauley, Bryan M, McGuire, Valerie, Ney, Britta, Olawaiye, Alexander, Orsulic, Sandra, Osorio, Ana, Paz‐Ares, Luis, Ramón y Cajal, Teresa, Rothstein, Joseph H, Ruebner, Matthias, Schoemaker, Minouk J, Shah, Mitul, Sharma, Raghwa, Sherman, Mark E, Shvetsov, Yurii B, Singh, Naveena, Steed, Helen, Storr, Sarah J, Talhouk, Aline, Traficante, Nadia, Wang, Chen, Whittemore, Alice S, Widschwendter, Martin, Wilkens, Lynne R, Winham, Stacey J, Benitez, Javier, Berchuck, Andrew, Bowtell, David D, dos Reis, Francisco J Candido, Campbell, Ian, Cook, Linda S, DeFazio, Anna, Doherty, Jennifer A, Fasching, Peter A, Fortner, Renée T, García, María J, Goodman, Marc T, Goode, Ellen L, Gronwald, Jacek, Huntsman, David G, Karlan, Beth Y, Kelemen, Linda E, Kommoss, Stefan, Le, Nhu D, and Martin, Stewart G
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Reproductive Medicine ,Biomedical and Clinical Sciences ,Oncology and Carcinogenesis ,Cancer ,Rare Diseases ,Ovarian Cancer ,Clinical Research ,Aetiology ,2.1 Biological and endogenous factors ,Humans ,Female ,Tumor Suppressor Protein p53 ,Ovarian Neoplasms ,Carcinoma ,Ovarian Epithelial ,Carcinoma ,Endometrioid ,ovarian cancer ,high-grade serous carcinoma ,endometrioid ,clear cell ,TP53 ,p53 ,prognosis ,AOCS Group ,Clinical sciences - Abstract
Our objective was to test whether p53 expression status is associated with survival for women diagnosed with the most common ovarian carcinoma histotypes (high-grade serous carcinoma [HGSC], endometrioid carcinoma [EC], and clear cell carcinoma [CCC]) using a large multi-institutional cohort from the Ovarian Tumor Tissue Analysis (OTTA) consortium. p53 expression was assessed on 6,678 cases represented on tissue microarrays from 25 participating OTTA study sites using a previously validated immunohistochemical (IHC) assay as a surrogate for the presence and functional effect of TP53 mutations. Three abnormal expression patterns (overexpression, complete absence, and cytoplasmic) and the normal (wild type) pattern were recorded. Survival analyses were performed by histotype. The frequency of abnormal p53 expression was 93.4% (4,630/4,957) in HGSC compared to 11.9% (116/973) in EC and 11.5% (86/748) in CCC. In HGSC, there were no differences in overall survival across the abnormal p53 expression patterns. However, in EC and CCC, abnormal p53 expression was associated with an increased risk of death for women diagnosed with EC in multivariate analysis compared to normal p53 as the reference (hazard ratio [HR] = 2.18, 95% confidence interval [CI] 1.36-3.47, p = 0.0011) and with CCC (HR = 1.57, 95% CI 1.11-2.22, p = 0.012). Abnormal p53 was also associated with shorter overall survival in The International Federation of Gynecology and Obstetrics stage I/II EC and CCC. Our study provides further evidence that functional groups of TP53 mutations assessed by abnormal surrogate p53 IHC patterns are not associated with survival in HGSC. In contrast, we validate that abnormal p53 IHC is a strong independent prognostic marker for EC and demonstrate for the first time an independent prognostic association of abnormal p53 IHC with overall survival in patients with CCC.
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- 2023
12. The genetic basis of endometriosis and comorbidity with other pain and inflammatory conditions
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Rahmioglu, Nilufer, Mortlock, Sally, Ghiasi, Marzieh, Møller, Peter L, Stefansdottir, Lilja, Galarneau, Geneviève, Turman, Constance, Danning, Rebecca, Law, Matthew H, Sapkota, Yadav, Christofidou, Paraskevi, Skarp, Sini, Giri, Ayush, Banasik, Karina, Krassowski, Michal, Lepamets, Maarja, Marciniak, Błażej, Nõukas, Margit, Perro, Danielle, Sliz, Eeva, Sobalska-Kwapis, Marta, Thorleifsson, Gudmar, Topbas-Selcuki, Nura F, Vitonis, Allison, Westergaard, David, Arnadottir, Ragnheidur, Burgdorf, Kristoffer S, Campbell, Archie, Cheuk, Cecilia SK, Clementi, Caterina, Cook, James, De Vivo, Immaculata, DiVasta, Amy, Dorien, O, Donoghue, Jacqueline F, Edwards, Todd, Fontanillas, Pierre, Fung, Jenny N, Geirsson, Reynir T, Girling, Jane E, Harkki, Paivi, Harris, Holly R, Healey, Martin, Heikinheimo, Oskari, Holdsworth-Carson, Sarah, Hostettler, Isabel C, Houlden, Henry, Houshdaran, Sahar, Irwin, Juan C, Jarvelin, Marjo-Riitta, Kamatani, Yoichiro, Kennedy, Stephen H, Kepka, Ewa, Kettunen, Johannes, Kubo, Michiaki, Kulig, Bartosz, Kurra, Venla, Laivuori, Hannele, Laufer, Marc R, Lindgren, Cecilia M, MacGregor, Stuart, Mangino, Massimo, Martin, Nicholas G, Matalliotaki, Charoula, Matalliotakis, Michail, Murray, Alison D, Ndungu, Anne, Nezhat, Camran, Olsen, Catherine M, Opoku-Anane, Jessica, Padmanabhan, Sandosh, Paranjpe, Manish, Peters, Maire, Polak, Grzegorz, Porteous, David J, Rabban, Joseph, Rexrode, Kathyrn M, Romanowicz, Hanna, Saare, Merli, Saavalainen, Liisu, Schork, Andrew J, Sen, Sushmita, Shafrir, Amy L, Siewierska-Górska, Anna, Słomka, Marcin, Smith, Blair H, Smolarz, Beata, Szaflik, Tomasz, Szyłło, Krzysztof, Takahashi, Atsushi, Terry, Kathryn L, Tomassetti, Carla, Treloar, Susan A, Vanhie, Arne, Vincent, Katy, Vo, Kim C, Werring, David J, Zeggini, Eleftheria, Zervou, Maria I, and Adachi, Sosuke
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Biological Sciences ,Genetics ,Contraception/Reproduction ,Clinical Research ,Endometriosis ,Prevention ,Pain Research ,Chronic Pain ,Infertility ,2.1 Biological and endogenous factors ,Aetiology ,Female ,Humans ,Genetic Predisposition to Disease ,Genome-Wide Association Study ,Pain ,Comorbidity ,DBDS Genomic Consortium ,FinnGen Study ,FinnGen Endometriosis Taskforce ,Celmatix Research Team ,23andMe Research Team ,Medical and Health Sciences ,Developmental Biology ,Agricultural biotechnology ,Bioinformatics and computational biology - Abstract
Endometriosis is a common condition associated with debilitating pelvic pain and infertility. A genome-wide association study meta-analysis, including 60,674 cases and 701,926 controls of European and East Asian descent, identified 42 genome-wide significant loci comprising 49 distinct association signals. Effect sizes were largest for stage 3/4 disease, driven by ovarian endometriosis. Identified signals explained up to 5.01% of disease variance and regulated expression or methylation of genes in endometrium and blood, many of which were associated with pain perception/maintenance (SRP14/BMF, GDAP1, MLLT10, BSN and NGF). We observed significant genetic correlations between endometriosis and 11 pain conditions, including migraine, back and multisite chronic pain (MCP), as well as inflammatory conditions, including asthma and osteoarthritis. Multitrait genetic analyses identified substantial sharing of variants associated with endometriosis and MCP/migraine. Targeted investigations of genetically regulated mechanisms shared between endometriosis and other pain conditions are needed to aid the development of new treatments and facilitate early symptomatic intervention.
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- 2023
13. Multiscale ecological resilience in braided rivers
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Harris, Holly A.L., primary, Tonkin, Jonathan D., additional, and McIntosh, Angus R., additional
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- 2024
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14. Contributors
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Banerjee, Sumana, primary, Beisel, Jean-Nicolas, additional, Bellido-Leiva, Francisco, additional, Bentley, Dianne, additional, Bisht, Tarun, additional, Bouska, Kristen, additional, Brierley, Gary, additional, Byron, Neil, additional, Caplan, Todd R., additional, Chaffin, Brian C., additional, Chowdhury, A. Ishtiaque A., additional, Conley, Will C., additional, Corenblit, Dov, additional, Cosens, Barbara, additional, Cossart, Robert, additional, Craig, Robin K., additional, Cremin, Emilie, additional, Cunningham, Shaun C., additional, Death, Russell G., additional, DeBoer, Jason A., additional, Delong, Michael D., additional, Doody, Tanya M., additional, Doyle, Martin, additional, Dufour, Simon, additional, Flint, Courtney G., additional, Fraser, Anthony W., additional, Fremier, Alexander K., additional, Fryirs, Kirstie, additional, Fuller, Ian C., additional, Gao, Sicong, additional, Harris, Holly A.L., additional, Heger, Tina, additional, Henderson, Leonard A., additional, Henderson, Andrew C.G., additional, Hensengerth, Oliver, additional, Hensley, Morika Vorenberg, additional, Holley, Cameron, additional, Holway, Joseph, additional, Inaho, Bega, additional, Jeschke, Jonathan M., additional, Jones, C. Nathan, additional, Killgore, K. Jack, additional, Kleiss, Barbara A., additional, Large, Andrew R.G., additional, Larkin, Zacchary, additional, Le, Hue, additional, Liébault, Frédéric, additional, Lininger, Katherine, additional, Lund, Jay, additional, Magilligan, Francis J., additional, Martin, Paul, additional, McCarthy, Terence, additional, McDonald, Jim, additional, McInerney, Paul J., additional, McIntosh, Angus R., additional, McKenna, Chad, additional, McMillan, Alex, additional, Milczarek, Mike, additional, Moggridge, Bradley J., additional, Morrison, Ryan R., additional, Murdoch, Lindsay, additional, Murshed, Sonia B., additional, Nally, Ralph Mac, additional, Nislow, Keith H., additional, O'Connor, Jack, additional, Ochs, Clifford, additional, Palmer, Richard E., additional, Parsons, Melissa, additional, Peek, Ryan, additional, Phillips, Jonathan, additional, Piégay, Hervé, additional, Pile, Jesse, additional, Ralph, Tim, additional, Renaud, Fabrice G., additional, Sabo, John L., additional, Saleeba, Mason, additional, Salgado, Jorge, additional, Scown, Murray W., additional, Srinivasan, Jaishri, additional, Steiger, Johannes, additional, Thompson, Ross M., additional, Thoms, Martin C., additional, Thomson, James R., additional, Tonkin, Jonathan D., additional, Tooth, Stephen, additional, Tri Van, P.D., additional, Tunnicliffe, Jon, additional, Van Looy, Kris, additional, Vu, Anh, additional, Walton, Richard E., additional, Wise, Russell M., additional, Wohl, Ellen, additional, Wolter, Christian, additional, Yarnell, Sarah, additional, and Yarrao, Markson, additional
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- 2024
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15. Increased FOXJ1 protein expression is associated with improved overall survival in high-grade serous ovarian carcinoma: an Ovarian Tumor Tissue Analysis Consortium Study
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Weir, Ashley, Kang, Eun-Young, Meagher, Nicola S, Nelson, Gregg S, Ghatage, Prafull, Lee, Cheng-Han, Riggan, Marjorie J, Gentry-Maharaj, Aleksandra, Ryan, Andy, Singh, Naveena, Widschwendter, Martin, Alsop, Jennifer, Anglesio, Michael S, Beckmann, Matthias W, Berger, Jessica, Bisinotto, Christiani, Boros, Jessica, Brand, Alison H, Brenton, James D, Brooks-Wilson, Angela, Carney, Michael E, Cunningham, Julie M, Cushing-Haugen, Kara L, Cybulski, Cezary, Elishaev, Esther, Erber, Ramona, Fereday, Sian, Fischer, Anna, Paz-Ares, Luis, Gayarre, Javier, Gilks, Blake C, Grube, Marcel, Harnett, Paul R, Harris, Holly R, Hartmann, Arndt, Hein, Alexander, Hendley, Joy, Hernandez, Brenda Y, Heublein, Sabine, Huang, Yajue, Huzarski, Tomasz, Jakubowska, Anna, Jimenez-Linan, Mercedes, Kennedy, Catherine J, Kommoss, Felix KF, Koziak, Jennifer M, Kraemer, Bernhard, Le, Nhu D, Lesnock, Jaime, Lester, Jenny, Lubiński, Jan, Menkiszak, Janusz, Ney, Britta, Olawaiye, Alexander, Orsulic, Sandra, Osorio, Ana, Robles-Díaz, Luis, Ruebner, Matthias, Shah, Mitul, Sharma, Raghwa, Shvetsov, Yurii B, Steed, Helen, Talhouk, Aline, Taylor, Sarah E, Traficante, Nadia, Vierkant, Robert A, Wang, Chen, Wilkens, Lynne R, Winham, Stacey J, Benitez, Javier, Berchuck, Andrew, Bowtell, David D, Candido dos Reis, Francisco J, Cook, Linda S, DeFazio, Anna, Doherty, Jennifer A, Fasching, Peter A, García, María J, Goode, Ellen L, Goodman, Marc T, Gronwald, Jacek, Huntsman, David G, Karlan, Beth Y, Kommoss, Stefan, Modugno, Francesmary, Schildkraut, Joellen M, Sinn, Hans-Peter, Staebler, Annette, Kelemen, Linda E, Ford, Caroline E, Menon, Usha, Pharoah, Paul DP, Köbel, Martin, and Ramus, Susan J
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Biomedical and Clinical Sciences ,Oncology and Carcinogenesis ,Genetics ,Ovarian Cancer ,Clinical Research ,Rare Diseases ,Cancer ,Aetiology ,2.1 Biological and endogenous factors ,Humans ,Female ,Ovarian Neoplasms ,Prognosis ,Survival Analysis ,RNA ,Messenger ,Cystadenocarcinoma ,Serous ,Biomarkers ,Tumor ,Forkhead Transcription Factors ,AOCs group ,Public Health and Health Services ,Oncology & Carcinogenesis ,Oncology and carcinogenesis - Abstract
BackgroundRecently, we showed a >60% difference in 5-year survival for patients with tubo-ovarian high-grade serous carcinoma (HGSC) when stratified by a 101-gene mRNA expression prognostic signature. Given the varied patient outcomes, this study aimed to translate prognostic mRNA markers into protein expression assays by immunohistochemistry and validate their survival association in HGSC.MethodsTwo prognostic genes, FOXJ1 and GMNN, were selected based on high-quality antibodies, correlation with protein expression and variation in immunohistochemical scores in a preliminary cohort (n = 134 and n = 80, respectively). Six thousand four hundred and thirty-four (FOXJ1) and 5470 (GMNN) formalin-fixed, paraffin-embedded ovarian neoplasms (4634 and 4185 HGSC, respectively) represented on tissue microarrays from the Ovarian Tumor Tissue Analysis consortium underwent immunohistochemical staining and scoring, then univariate and multivariate survival analysis.ResultsConsistent with mRNA, FOXJ1 protein expression exhibited a linear, increasing association with improved overall survival in HGSC patients. Women with >50% expression had the most favourable outcomes (HR = 0.78, 95% CI 0.67-0.91, p 35% GMNN expression showed a trend for better outcomes, though this was not significant.ConclusionWe provide foundational evidence for the prognostic value of FOXJ1 in HGSC, validating the prior mRNA-based prognostic association by immunohistochemistry.
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- 2023
16. Profiling the immune landscape in mucinous ovarian carcinoma.
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Meagher, Nicola, Hamilton, Phineas, Milne, Katy, Thornton, Shelby, Harris, Bronwyn, Weir, Ashley, Alsop, Jennifer, Bisinoto, Christiani, Brenton, James, Brooks-Wilson, Angela, Chiu, Derek, Cushing-Haugen, Kara, Fereday, Sian, Garsed, Dale, Gayther, Simon, Gentry-Maharaj, Aleksandra, Gilks, Blake, Jimenez-Linan, Mercedes, Kennedy, Catherine, Le, Nhu, Piskorz, Anna, Riggan, Marjorie, Shah, Mitul, Singh, Naveena, Talhouk, Aline, Widschwendter, Martin, Bowtell, David, Candido Dos Reis, Francisco, Cook, Linda, Fortner, Renée, García, María, Harris, Holly, Huntsman, David, Köbel, Martin, Menon, Usha, Pharoah, Paul, Doherty, Jennifer, Anglesio, Michael, Pike, Malcolm, Pearce, Celeste, Friedlander, Michael, DeFazio, Anna, Nelson, Brad, Ramus, Susan, and Karnezis, Anthony
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Immune infiltrate ,Mucinous ovarian carcinoma ,Rare histotype ,Humans ,Female ,B7-H1 Antigen ,Carcinoma ,Ovarian Epithelial ,Ovarian Neoplasms ,CD8-Positive T-Lymphocytes ,Forkhead Transcription Factors ,Lymphocytes ,Tumor-Infiltrating ,Tumor Microenvironment - Abstract
OBJECTIVE: Mucinous ovarian carcinoma (MOC) is a rare histotype of ovarian cancer, with low response rates to standard chemotherapy, and very poor survival for patients diagnosed at advanced stage. There is a limited understanding of the MOC immune landscape, and consequently whether immune checkpoint inhibitors could be considered for a subset of patients. METHODS: We performed multicolor immunohistochemistry (IHC) and immunofluorescence (IF) on tissue microarrays in a cohort of 126 MOC patients. Cell densities were calculated in the epithelial and stromal components for tumor-associated macrophages (CD68+/PD-L1+, CD68+/PD-L1-), T cells (CD3+/CD8-, CD3+/CD8+), putative T-regulatory cells (Tregs, FOXP3+), B cells (CD20+/CD79A+), plasma cells (CD20-/CD79a+), and PD-L1+ and PD-1+ cells, and compared these values with clinical factors. Univariate and multivariable Cox Proportional Hazards assessed overall survival. Unsupervised k-means clustering identified patient subsets with common patterns of immune cell infiltration. RESULTS: Mean densities of PD1+ cells, PD-L1- macrophages, CD4+ and CD8+ T cells, and FOXP3+ Tregs were higher in the stroma compared to the epithelium. Tumors from advanced (Stage III/IV) MOC had greater epithelial infiltration of PD-L1- macrophages, and fewer PD-L1+ macrophages compared with Stage I/II cancers (p = 0.004 and p = 0.014 respectively). Patients with high epithelial density of FOXP3+ cells, CD8+/FOXP3+ cells, or PD-L1- macrophages, had poorer survival, and high epithelial CD79a + plasma cells conferred better survival, all upon univariate analysis only. Clustering showed that most MOC (86%) had an immune depleted (cold) phenotype, with only a small proportion (11/76,14%) considered immune inflamed (hot) based on T cell and PD-L1 infiltrates. CONCLUSION: In summary, MOCs are mostly immunogenically cold, suggesting they may have limited response to current immunotherapies.
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- 2023
17. Modification of the Association Between Frequent Aspirin Use and Ovarian Cancer Risk: A Meta-Analysis Using Individual-Level Data From Two Ovarian Cancer Consortia
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Hurwitz, Lauren M, Townsend, Mary K, Jordan, Susan J, Patel, Alpa V, Teras, Lauren R, Lacey, James V, Doherty, Jennifer A, Harris, Holly R, Goodman, Marc T, Shvetsov, Yurii B, Modugno, Francesmary, Moysich, Kirsten B, Robien, Kim, Prizment, Anna, Schildkraut, Joellen M, Berchuck, Andrew, Fortner, Renée T, Chan, Andrew T, Wentzensen, Nicolas, Hartge, Patricia, Sandler, Dale P, O'Brien, Katie M, Anton-Culver, Hoda, Ziogas, Argyrios, Menon, Usha, Ramus, Susan J, Pearce, Celeste Leigh, Wu, Anna H, White, Emily, Peters, Ulrike, Webb, Penelope M, Tworoger, Shelley S, and Trabert, Britton
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Biomedical and Clinical Sciences ,Oncology and Carcinogenesis ,Prevention ,Cancer ,Patient Safety ,Clinical Research ,Ovarian Cancer ,Rare Diseases ,Breast Cancer ,3.3 Nutrition and chemoprevention ,Prevention of disease and conditions ,and promotion of well-being ,Female ,Humans ,Aspirin ,Endometriosis ,Ovarian Neoplasms ,Case-Control Studies ,Risk Factors ,Clinical Sciences ,Oncology & Carcinogenesis ,Oncology and carcinogenesis - Abstract
PurposeFrequent aspirin use has been associated with reduced ovarian cancer risk, but no study has comprehensively assessed for effect modification. We leveraged harmonized, individual-level data from 17 studies to examine the association between frequent aspirin use and ovarian cancer risk, overall and across subgroups of women with other ovarian cancer risk factors.MethodsNine cohort studies from the Ovarian Cancer Cohort Consortium (n = 2,600 cases) and eight case-control studies from the Ovarian Cancer Association Consortium (n = 5,726 cases) were included. We used Cox regression and logistic regression to assess study-specific associations between frequent aspirin use (≥ 6 days/week) and ovarian cancer risk and combined study-specific estimates using random-effects meta-analysis. We conducted analyses within subgroups defined by individual ovarian cancer risk factors (endometriosis, obesity, family history of breast/ovarian cancer, nulliparity, oral contraceptive use, and tubal ligation) and by number of risk factors (0, 1, and ≥ 2).ResultsOverall, frequent aspirin use was associated with a 13% reduction in ovarian cancer risk (95% CI, 6 to 20), with no significant heterogeneity by study design (P = .48) or histotype (P = .60). Although no association was observed among women with endometriosis, consistent risk reductions were observed among all other subgroups defined by ovarian cancer risk factors (relative risks ranging from 0.79 to 0.93, all P-heterogeneity > .05), including women with ≥ 2 risk factors (relative risk, 0.81; 95% CI, 0.73 to 0.90).ConclusionThis study, the largest to-date on aspirin use and ovarian cancer, provides evidence that frequent aspirin use is associated with lower ovarian cancer risk regardless of the presence of most other ovarian cancer risk factors. Risk reductions were also observed among women with multiple risk factors, providing proof of principle that chemoprevention programs with frequent aspirin use could target higher-risk subgroups.
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- 2022
18. Gene expression profiling of mucinous ovarian tumors and comparison with upper and lower gastrointestinal tumors identifies markers associated with adverse outcomes.
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Meagher, Nicola S, Gorringe, Kylie L, Wakefield, Matthew, Bolithon, Adelyn, Pang, Chi Nam Ignatius, Chiu, Derek S, Anglesio, Michael S, Mallitt, Kylie-Ann, Doherty, Jennifer A, Harris, Holly R, Schildkraut, Joellen M, Berchuck, Andrew, Cushing-Haugen, Kara L, Chezar, Ksenia, Chou, Angela, Tan, Adeline, Alsop, Jennifer, Barlow, Ellen, Beckmann, Matthias W, Boros, Jessica, Bowtell, David DL, Group, for the AOCS, Brand, Alison H, Brenton, James D, Campbell, Ian, Cheasley, Dane, Cohen, Joshua, Cybulski, Cezary, Elishaev, Esther, Erber, Ramona, Farrell, Rhonda, Fischer, Anna, Fu, Zhuxuan, Gilks, Blake, Gill, Anthony J, Initiative, for the Australian Pancreatic Genome, Gourley, Charlie, Grube, Marcel, Harnett, Paul R, Hartmann, Arndt, Hettiaratchi, Anusha, Høgdall, Claus K, Huzarski, Tomasz, Jakubowska, Anna, Jimenez-Linan, Mercedes, Kennedy, Catherine J, Kim, Byoung-Gie, Kim, Jae-Weon, Kim, Jae-Hoon, Klett, Kayla, Koziak, Jennifer M, Lai, Tiffany, Laslavic, Angela, Lester, Jenny, Leung, Yee, Li, Na, Liauw, Winston, Lim, Belle WX, Linder, Anna, Lubiński, Jan, Mahale, Sakshi, Mateoiu, Constantina, McInerny, Simone, Menkiszak, Janusz, Minoo, Parham, Mittelstadt, Suzana, Morris, David, Orsulic, Sandra, Park, Sang-Yoon, Pearce, Celeste Leigh, Pearson, John V, Pike, Malcolm C, Quinn, Carmel M, Mohan, Ganendra Raj, Rao, Jianyu, Riggan, Marjorie J, Ruebner, Matthias, Salfinger, Stuart, Scott, Clare L, Shah, Mitul, Steed, Helen, Stewart, Colin JR, Subramanian, Deepak, Sung, Soseul, Tang, Katrina, Timpson, Paul, Ward, Robyn L, Wiedenhoefer, Rebekka, Thorne, Heather, Investigators, for the kConFab, Cohen, Paul A, Crowe, Philip, Fasching, Peter A, Gronwald, Jacek, Hawkins, Nicholas J, Høgdall, Estrid, Huntsman, David G, James, Paul A, Karlan, Beth Y, and Kelemen, Linda E
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Biomedical and Clinical Sciences ,Oncology and Carcinogenesis ,Ovarian Cancer ,Rare Diseases ,Cancer ,Digestive Diseases ,Genetics ,4.1 Discovery and preclinical testing of markers and technologies ,Detection ,screening and diagnosis ,Female ,Humans ,Neoplasm Staging ,Ovarian Neoplasms ,Carcinoma ,Ovarian Epithelial ,Adenocarcinoma ,Mucinous ,Prognosis ,Gastrointestinal Neoplasms ,AOCS Group ,Australian Pancreatic Genome Initiative ,kConFab Investigators ,Oncology & Carcinogenesis ,Clinical sciences ,Oncology and carcinogenesis - Abstract
PurposeAdvanced-stage mucinous ovarian carcinoma (MOC) has poor chemotherapy response and prognosis and lacks biomarkers to aid stage I adjuvant treatment. Differentiating primary MOC from gastrointestinal (GI) metastases to the ovary is also challenging due to phenotypic similarities. Clinicopathologic and gene-expression data were analyzed to identify prognostic and diagnostic features.Experimental designDiscovery analyses selected 19 genes with prognostic/diagnostic potential. Validation was performed through the Ovarian Tumor Tissue Analysis consortium and GI cancer biobanks comprising 604 patients with MOC (n = 333), mucinous borderline ovarian tumors (MBOT, n = 151), and upper GI (n = 65) and lower GI tumors (n = 55).ResultsInfiltrative pattern of invasion was associated with decreased overall survival (OS) within 2 years from diagnosis, compared with expansile pattern in stage I MOC [hazard ratio (HR), 2.77; 95% confidence interval (CI), 1.04-7.41, P = 0.042]. Increased expression of THBS2 and TAGLN was associated with shorter OS in MOC patients (HR, 1.25; 95% CI, 1.04-1.51, P = 0.016) and (HR, 1.21; 95% CI, 1.01-1.45, P = 0.043), respectively. ERBB2 (HER2) amplification or high mRNA expression was evident in 64 of 243 (26%) of MOCs, but only 8 of 243 (3%) were also infiltrative (4/39, 10%) or stage III/IV (4/31, 13%).ConclusionsAn infiltrative growth pattern infers poor prognosis within 2 years from diagnosis and may help select stage I patients for adjuvant therapy. High expression of THBS2 and TAGLN in MOC confers an adverse prognosis and is upregulated in the infiltrative subtype, which warrants further investigation. Anti-HER2 therapy should be investigated in a subset of patients. MOC samples clustered with upper GI, yet markers to differentiate these entities remain elusive, suggesting similar underlying biology and shared treatment strategies.
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- 2022
19. The Impact of the COVID-19 Pandemic on Older Women in the Women’s Health Initiative
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VoPham, Trang, Harris, Holly R, Tinker, Lesley F, Manson, JoAnn E, Meliker, Jaymie R, Wassertheil-Smoller, Sylvia, Shadyab, Aladdin H, Saquib, Nazmus, Anderson, Garnet L, and Shumaker, Sally A
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Health Services and Systems ,Biomedical and Clinical Sciences ,Clinical Sciences ,Health Sciences ,Infectious Diseases ,Aging ,Prevention ,Behavioral and Social Science ,Lung ,Clinical Research ,Emerging Infectious Diseases ,Management of diseases and conditions ,7.1 Individual care needs ,Generic health relevance ,Good Health and Well Being ,Female ,Humans ,Aged ,Aged ,80 and over ,Pandemics ,COVID-19 ,SARS-CoV-2 ,COVID-19 Testing ,Prospective Studies ,Women's Health ,Cohort study ,Living arrangements ,Well-being ,Gerontology ,Biomedical and clinical sciences ,Health sciences - Abstract
BackgroundThe coronavirus disease 2019 (COVID-19) pandemic is a health crisis of which older adults are a high-risk group for severe illness and mortality. The objectives of this article are to describe the methods and responses to a COVID-19 survey administered by the Women's Health Initiative (WHI) to assess the impact of the pandemic on older women.MethodsWHI is an ongoing prospective cohort study that recruited 161 808 postmenopausal women from 1993 to 1998. From June 2020 to October 2020, participants in active follow-up were surveyed by mail, phone, or online to assess health and well-being, living situations, lifestyle, health care, and self-reported COVID-19 testing, treatment, and preventive behaviors.ResultsOf 64 061 eligible participants, 49 695 (average age 83.6 years ± 5.6) completed the COVID-19 survey (response rate 77.6%). Many participants reported very good or good well-being (75.6%). Respondents reported being very concerned about the pandemic (51.1%; more common in urban compared to rural areas), with 6.9% reporting disruptions in living arrangements and 9.7% reporting changes in medication access. Participants (54.4%) reported physical activity levels were much less or somewhat less compared to levels before the pandemic, and this was more pronounced in urban areas versus rural areas (55.3% vs 44.4%). Participants engaged in preventive behaviors including wearing a face mask (93.2%). A total of 18.9% reported testing for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), among whom 3.5% (n = 311) reported testing positive.ConclusionsIn this nationwide survey of older U.S. women, the COVID-19 pandemic was associated with impacts on health and well-being, living situations, lifestyle, health care access, and SARS-CoV-2 testing and preventive behaviors.
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- 2022
20. Effects of risk factors for ovarian cancer in women with and without endometriosis
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Phung, Minh Tung, Muthukumar, Aruna, Trabert, Britton, Webb, Penelope M, Jordan, Susan J, Terry, Kathryn L, Cramer, Daniel W, Titus, Linda J, Risch, Harvey A, Doherty, Jennifer Anne, Harris, Holly R, Goodman, Marc T, Modugno, Francesmary, Moysich, Kirsten B, Jensen, Allan, Kjaer, Susanne K, Anton-Culver, Hoda, Ziogas, Argyrios, Berchuck, Andrew, Khoja, Lilah, Wu, Anna H, Pike, Malcolm C, Pearce, Celeste Leigh, and Lee, Alice W
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Biomedical and Clinical Sciences ,Oncology and Carcinogenesis ,Rare Diseases ,Contraception/Reproduction ,Cancer ,Prevention ,Endometriosis ,Aging ,Estrogen ,Clinical Research ,Ovarian Cancer ,Clinical Trials and Supportive Activities ,2.1 Biological and endogenous factors ,Aetiology ,Female ,Humans ,Talc ,Ovarian Neoplasms ,Carcinoma ,Ovarian Epithelial ,Risk Factors ,Case-Control Studies ,Estrogens ,ovarian cancer ,effect modification ,risk factors ,interactions ,Clinical Sciences ,Paediatrics and Reproductive Medicine ,Public Health and Health Services ,Obstetrics & Reproductive Medicine ,Reproductive medicine - Abstract
ObjectiveTo evaluate the associations between 10 well-established ovarian cancer risk factors and risk of ovarian cancer among women with vs. without endometriosis.DesignPooled analysis of 9 case-control studies in the Ovarian Cancer Association Consortium.SettingPopulation-based.Patient(s)We included 8,500 women with ovarian cancer, 13,592 control women.Intervention(s)Ten well-established ovarian cancer risk factors.Main outcome measure(s)Risk of ovarian cancer for women with and without endometriosis.Result(s)Most risk factor-ovarian cancer associations were similar when comparing women with and without endometriosis, and no interactions were statistically significant. However, body mass index (BMI) 25-
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- 2022
21. Finding connection “while everything is going to crap”: experiences in Recovery Colleges during the COVID-19 pandemic
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Harris, Holly, Shier, Rowen, Black, Georgia, Di Giandomenico, Anna, Lin, Elizabeth, Bellissimo, Gail, Rovet, Jordana, Gruszecki, Sam, and Soklaridis, Sophie
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- 2023
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22. The feeding siblings questionnaire (FSQ): Development of a self-report tool for parents with children aged 2–5 years
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Ayre, Susannah K., White, Melanie J., Harris, Holly A., Jansen, Elena, and Byrne, Rebecca A.
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- 2024
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23. Risk factors for long COVID syndrome in postmenopausal women with previously reported diagnosis of COVID-19
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Neuhouser, Marian L., Butt, Hamza Islam, Hu, Chengcheng, Shadyab, Aladdin H., Garcia, Lorena, Follis, Shawna, Mouton, Charles, Harris, Holly R., Wactawski-Wende, Jean, Gower, Emily W., Vitolins, Mara, Von Ah, Diane, Nassir, Rami, Karanth, Shama, Ng, Ted, Paskett, Electra, Manson, JoAnn E., and Chen, Zhao
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- 2024
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24. Correction: Polygenic risk modeling for prediction of epithelial ovarian cancer risk
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Dareng, Eileen O, Tyrer, Jonathan P, Barnes, Daniel R, Jones, Michelle R, Yang, Xin, Aben, Katja KH, Adank, Muriel A, Agata, Simona, Andrulis, Irene L, Anton-Culver, Hoda, Antonenkova, Natalia N, Aravantinos, Gerasimos, Arun, Banu K, Augustinsson, Annelie, Balmaña, Judith, Bandera, Elisa V, Barkardottir, Rosa B, Barrowdale, Daniel, Beckmann, Matthias W, Beeghly-Fadiel, Alicia, Benitez, Javier, Bermisheva, Marina, Bernardini, Marcus Q, Bjorge, Line, Black, Amanda, Bogdanova, Natalia V, Bonanni, Bernardo, Borg, Ake, Brenton, James D, Budzilowska, Agnieszka, Butzow, Ralf, Buys, Saundra S, Cai, Hui, Caligo, Maria A, Campbell, Ian, Cannioto, Rikki, Cassingham, Hayley, Chang-Claude, Jenny, Chanock, Stephen J, Chen, Kexin, Chiew, Yoke-Eng, Chung, Wendy K, Claes, Kathleen BM, Colonna, Sarah, Cook, Linda S, Couch, Fergus J, Daly, Mary B, Dao, Fanny, Davies, Eleanor, de la Hoya, Miguel, de Putter, Robin, Dennis, Joe, DePersia, Allison, Devilee, Peter, Diez, Orland, Ding, Yuan Chun, Doherty, Jennifer A, Domchek, Susan M, Dörk, Thilo, du Bois, Andreas, Dürst, Matthias, Eccles, Diana M, Eliassen, Heather A, Engel, Christoph, Evans, Gareth D, Fasching, Peter A, Flanagan, James M, Fortner, Renée T, Machackova, Eva, Friedman, Eitan, Ganz, Patricia A, Garber, Judy, Gensini, Francesca, Giles, Graham G, Glendon, Gord, Godwin, Andrew K, Goodman, Marc T, Greene, Mark H, Gronwald, Jacek, Hahnen, Eric, Haiman, Christopher A, Håkansson, Niclas, Hamann, Ute, Hansen, Thomas VO, Harris, Holly R, Hartman, Mikael, Heitz, Florian, Hildebrandt, Michelle AT, Høgdall, Estrid, Høgdall, Claus K, Hopper, John L, Huang, Ruea-Yea, Huff, Chad, Hulick, Peter J, Huntsman, David G, Imyanitov, Evgeny N, Isaacs, Claudine, Jakubowska, Anna, James, Paul A, and Janavicius, Ramunas
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GEMO Study Collaborators ,GC-HBOC Study Collaborators ,EMBRACE Collaborators ,OPAL Study Group ,AOCS Group ,KConFab Investigators ,HEBON Investigators ,OCAC Consortium ,CIMBA Consortium ,Genetics ,Clinical Sciences ,Genetics & Heredity - Published
- 2022
25. Polygenic risk modeling for prediction of epithelial ovarian cancer risk
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Dareng, Eileen O, Tyrer, Jonathan P, Barnes, Daniel R, Jones, Michelle R, Yang, Xin, Aben, Katja KH, Adank, Muriel A, Agata, Simona, Andrulis, Irene L, Anton-Culver, Hoda, Antonenkova, Natalia N, Aravantinos, Gerasimos, Arun, Banu K, Augustinsson, Annelie, Balmaña, Judith, Bandera, Elisa V, Barkardottir, Rosa B, Barrowdale, Daniel, Beckmann, Matthias W, Beeghly-Fadiel, Alicia, Benitez, Javier, Bermisheva, Marina, Bernardini, Marcus Q, Bjorge, Line, Black, Amanda, Bogdanova, Natalia V, Bonanni, Bernardo, Borg, Ake, Brenton, James D, Budzilowska, Agnieszka, Butzow, Ralf, Buys, Saundra S, Cai, Hui, Caligo, Maria A, Campbell, Ian, Cannioto, Rikki, Cassingham, Hayley, Chang-Claude, Jenny, Chanock, Stephen J, Chen, Kexin, Chiew, Yoke-Eng, Chung, Wendy K, Claes, Kathleen BM, Colonna, Sarah, Cook, Linda S, Couch, Fergus J, Daly, Mary B, Dao, Fanny, Davies, Eleanor, de la Hoya, Miguel, de Putter, Robin, Dennis, Joe, DePersia, Allison, Devilee, Peter, Diez, Orland, Ding, Yuan Chun, Doherty, Jennifer A, Domchek, Susan M, Dörk, Thilo, du Bois, Andreas, Dürst, Matthias, Eccles, Diana M, Eliassen, Heather A, Engel, Christoph, Evans, Gareth D, Fasching, Peter A, Flanagan, James M, Fortner, Renée T, Machackova, Eva, Friedman, Eitan, Ganz, Patricia A, Garber, Judy, Gensini, Francesca, Giles, Graham G, Glendon, Gord, Godwin, Andrew K, Goodman, Marc T, Greene, Mark H, Gronwald, Jacek, Hahnen, Eric, Haiman, Christopher A, Håkansson, Niclas, Hamann, Ute, Hansen, Thomas VO, Harris, Holly R, Hartman, Mikael, Heitz, Florian, Hildebrandt, Michelle AT, Høgdall, Estrid, Høgdall, Claus K, Hopper, John L, Huang, Ruea-Yea, Huff, Chad, Hulick, Peter J, Huntsman, David G, Imyanitov, Evgeny N, Isaacs, Claudine, Jakubowska, Anna, James, Paul A, and Janavicius, Ramunas
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Prevention ,Cancer ,Ovarian Cancer ,Rare Diseases ,Good Health and Well Being ,Bayes Theorem ,Breast Neoplasms ,Carcinoma ,Ovarian Epithelial ,Female ,Genetic Predisposition to Disease ,Humans ,Male ,Ovarian Neoplasms ,Polymorphism ,Single Nucleotide ,Prospective Studies ,Risk Factors ,GEMO Study Collaborators ,GC-HBOC Study Collaborators ,EMBRACE Collaborators ,OPAL Study Group ,AOCS Group ,KConFab Investigators ,HEBON Investigators ,OCAC Consortium ,CIMBA Consortium ,Genetics ,Clinical Sciences ,Genetics & Heredity - Abstract
Polygenic risk scores (PRS) for epithelial ovarian cancer (EOC) have the potential to improve risk stratification. Joint estimation of Single Nucleotide Polymorphism (SNP) effects in models could improve predictive performance over standard approaches of PRS construction. Here, we implemented computationally efficient, penalized, logistic regression models (lasso, elastic net, stepwise) to individual level genotype data and a Bayesian framework with continuous shrinkage, "select and shrink for summary statistics" (S4), to summary level data for epithelial non-mucinous ovarian cancer risk prediction. We developed the models in a dataset consisting of 23,564 non-mucinous EOC cases and 40,138 controls participating in the Ovarian Cancer Association Consortium (OCAC) and validated the best models in three populations of different ancestries: prospective data from 198,101 women of European ancestries; 7,669 women of East Asian ancestries; 1,072 women of African ancestries, and in 18,915 BRCA1 and 12,337 BRCA2 pathogenic variant carriers of European ancestries. In the external validation data, the model with the strongest association for non-mucinous EOC risk derived from the OCAC model development data was the S4 model (27,240 SNPs) with odds ratios (OR) of 1.38 (95% CI: 1.28-1.48, AUC: 0.588) per unit standard deviation, in women of European ancestries; 1.14 (95% CI: 1.08-1.19, AUC: 0.538) in women of East Asian ancestries; 1.38 (95% CI: 1.21-1.58, AUC: 0.593) in women of African ancestries; hazard ratios of 1.36 (95% CI: 1.29-1.43, AUC: 0.592) in BRCA1 pathogenic variant carriers and 1.49 (95% CI: 1.35-1.64, AUC: 0.624) in BRCA2 pathogenic variant carriers. Incorporation of the S4 PRS in risk prediction models for ovarian cancer may have clinical utility in ovarian cancer prevention programs.
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- 2022
26. Laparoscopically confirmed endometriosis and anti-Müllerian hormone levels: Findings from the Nurses' Health Study II
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Farland, Leslie V., Valenti, Michelle, Degnan, William J., III, Bertone-Johnson, Elizabeth R., Harris, Holly R., DiVasta, Amy D., Rexrode, Kathryn M., Eliassen, A. Heather, and Missmer, Stacey A.
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- 2024
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27. Pericapsular Nerve Group (PENG) Block Results in Significant Opioid Reduction in Total Hip Arthroplasty: A Retrospective Analysis
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Leyba, Evan, Harris, Holly, Gallardo, Olana, Morgan, Whitney, and Cornelius, Brian
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- 2024
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28. Early childhood appetitive traits and eating disorder symptoms in adolescence: a 10-year longitudinal follow-up study in the Netherlands and the UK
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Derks, Ivonne P M, Nas, Zeynep, Harris, Holly A, Kininmonth, Alice R, Treasure, Janet, Jansen, Pauline W, and Llewellyn, Clare H
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- 2024
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29. Optimizing Care for Autistic Patients in Health Care Settings: A Scoping Review and Call to Action
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Harris, Holly K., Weissman, Laura, Friedlaender, Eron Y., Neumeyer, Ann M., Friedman, Alexander J., Spence, Sarah J., Rotman, Chloe, Krauss, Shari, Broder-Fingert, Sarabeth, and Weitzman, Carol
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- 2024
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30. High pre-diagnosis inflammation-related risk score associated with decreased ovarian cancer survival
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Brieger, Katharine K, Phung, Minh Tung, Mukherjee, Bhramar, Bakulski, Kelly M, Anton-Culver, Hoda, Bandera, Elisa V, Bowtell, David DL, Cramer, Daniel W, DeFazio, Anna, Doherty, Jennifer A, Fereday, Sian, Fortner, Renée Turzanski, Gentry-Maharaj, Aleksandra, Goode, Ellen L, Goodman, Marc T, Harris, Holly R, Matsuo, Keitaro, Menon, Usha, Modugno, Francesmary, Moysich, Kirsten B, Qin, Bo, Ramus, Susan J, Risch, Harvey A, Rossing, Mary Anne, Schildkraut, Joellen M, Trabert, Britton, Vierkant, Robert A, Winham, Stacey J, Wentzensen, Nicolas, Wu, Anna H, Ziogas, Argyrios, Khoja, Lilah, Cho, Kathleen R, McLean, Karen, Richardson, Jean, Grout, Bronwyn, Chase, Anne, Deurloo, Cindy McKinnon, Odunsi, Kunle, Nelson, Brad H, Brenton, James D, Terry, Kathryn L, Pharoah, Paul DP, Berchuck, Andrew, Hanley, Gillian E, Webb, Penelope M, Pike, Malcolm C, and Pearce, Celeste Leigh
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Epidemiology ,Biomedical and Clinical Sciences ,Health Sciences ,Tobacco Smoke and Health ,Prevention ,Ovarian Cancer ,Tobacco ,Cancer ,Rare Diseases ,Aetiology ,2.1 Biological and endogenous factors ,Good Health and Well Being ,Aged ,Carcinoma ,Ovarian Epithelial ,Female ,Health Behavior ,Humans ,Inflammation ,Middle Aged ,Ovarian Neoplasms ,Proportional Hazards Models ,Risk Assessment ,Ovarian Cancer Association Consortium ,Medical and Health Sciences ,Biomedical and clinical sciences ,Health sciences - Abstract
BackgroundThere is suggestive evidence that inflammation is related to ovarian cancer survival. However, more research is needed to identify inflammation-related factors that are associated with ovarian cancer survival and to determine their combined effects.MethodsThis analysis used pooled data on 8,147 women with invasive epithelial ovarian cancer from the Ovarian Cancer Association Consortium. The prediagnosis inflammation-related exposures of interest included alcohol use; aspirin use; other nonsteroidal anti-inflammatory drug use; body mass index; environmental tobacco smoke exposure; history of pelvic inflammatory disease, polycystic ovarian syndrome, and endometriosis; menopausal hormone therapy use; physical inactivity; smoking status; and talc use. Using Cox proportional hazards models, the relationship between each exposure and survival was assessed in 50% of the data. A weighted inflammation-related risk score (IRRS) was developed, and its association with survival was assessed using Cox proportional hazards models in the remaining 50% of the data.ResultsThere was a statistically significant trend of increasing risk of death per quartile of the IRRS [HR = 1.09; 95% confidence interval (CI), 1.03-1.14]. Women in the upper quartile of the IRRS had a 31% higher death rate compared with the lowest quartile (95% CI, 1.11-1.54).ConclusionsA higher prediagnosis IRRS was associated with an increased mortality risk after an ovarian cancer diagnosis. Further investigation is warranted to evaluate whether postdiagnosis exposures are also associated with survival.ImpactGiven that pre- and postdiagnosis exposures are often correlated and many are modifiable, our study results can ultimately motivate the development of behavioral recommendations to enhance survival among patients with ovarian cancer.
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- 2022
31. Endometriosis and menopausal hormone therapy impact the hysterectomy-ovarian cancer association
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Khoja, Lilah, Weber, Rachel Palmieri, Group, The Australian Ovarian Cancer Study, Webb, Penelope M, Jordan, Susan J, Muthukumar, Aruna, Chang-Claude, Jenny, Fortner, Renée T, Jensen, Allan, Kjaer, Susanne K, Risch, Harvey, Doherty, Jennifer Anne, Harris, Holly R, Goodman, Marc T, Modugno, Francesmary, Moysich, Kirsten, Berchuck, Andrew, Schildkraut, Joellen M, Cramer, Daniel, Terry, Kathryn L, Anton-Culver, Hoda, Ziogas, Argyrios, Phung, Minh Tung, Hanley, Gillian E, Wu, Anna H, Mukherjee, Bhramar, McLean, Karen, Cho, Kathleen, Pike, Malcolm C, Pearce, Celeste Leigh, and Lee, Alice W
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Reproductive Medicine ,Biomedical and Clinical Sciences ,Oncology and Carcinogenesis ,Cancer ,Endometriosis ,Ovarian Cancer ,Rare Diseases ,Contraception/Reproduction ,Clinical Research ,Estrogen ,2.1 Biological and endogenous factors ,Aetiology ,Case-Control Studies ,Estrogen Replacement Therapy ,Female ,Humans ,Hysterectomy ,Menopause ,Ovarian Neoplasms ,Ovarian cancer ,Hormone therapy ,Australian Ovarian Cancer Study Group ,Paediatrics and Reproductive Medicine ,Oncology & Carcinogenesis ,Clinical sciences ,Oncology and carcinogenesis ,Reproductive medicine - Abstract
ObjectiveTo evaluate the association between hysterectomy and ovarian cancer, and to understand how hormone therapy (HT) use and endometriosis affect this association.MethodsWe conducted a pooled analysis of self-reported data from 11 case-control studies in the Ovarian Cancer Association Consortium (OCAC). Women with (n = 5350) and without ovarian cancer (n = 7544) who never used HT or exclusively used either estrogen-only therapy (ET) or estrogen+progestin therapy (EPT) were included. Risk of invasive epithelial ovarian cancer adjusted for duration of ET and EPT use and stratified on history of endometriosis was determined using odds ratios (ORs) with 95% confidence intervals (CIs).ResultsOverall and among women without endometriosis, there was a positive association between ovarian cancer risk and hysterectomy (OR = 1.19, 95% CI 1.09-1.31 and OR = 1.20, 95% CI 1.09-1.32, respectively), but no association upon adjusting for duration of ET and EPT use (OR = 1.04, 95% CI 0.94-1.16 and OR = 1.06, 95% CI 0.95-1.18, respectively). Among women with a history of endometriosis, there was a slight inverse association between hysterectomy and ovarian cancer risk (OR = 0.93, 95% CI 0.69-1.26), but this association became stronger and statistically significant after adjusting for duration of ET and EPT use (OR = 0.69, 95% CI 0.48-0.99).ConclusionsThe hysterectomy-ovarian cancer association is complex and cannot be understood without considering duration of ET and EPT use and history of endometriosis. Failure to take these exposures into account in prior studies casts doubt on their conclusions. Overall, hysterectomy is not risk-reducing for ovarian cancer, however the inverse association among women with endometriosis warrants further investigation.
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- 2022
32. Exploring the Recovery Phenomenon from Adolescents’ Perspective: A Qualitative Study
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Arbour, Simone, Chiu, Mary, Paul, Sayani, Battistelli, Rachael, and Harris, Holly
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- 2023
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33. A prospective study of dietary patterns and the incidence of endometriosis diagnosis
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Dougan, Marcelle M., Fest, Sable, Cushing-Haugen, Kara, Farland, Leslie V., Chavarro, Jorge, Harris, Holly R., and Missmer, Stacey A.
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- 2024
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34. Food Parenting Practices and Child Eating Behaviors in Australian Families: A Cross-Sectional Sibling Design
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Ayre, Susannah K., Harris, Holly A., White, Melanie J., and Byrne, Rebecca A.
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- 2024
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35. An epigenome-wide association study of child appetitive traits and DNA methylation
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Harris, Holly A., Friedman, Chloe, Starling, Anne P., Dabelea, Dana, Johnson, Susan L., Fuemmeler, Bernard F., Jima, Dereje, Murphy, Susan K., Hoyo, Cathrine, Jansen, Pauline W., Felix, Janine F., and Mulder, Rosa H.
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- 2023
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36. Population-based targeted sequencing of 54 candidate genes identifies PALB2 as a susceptibility gene for high-grade serous ovarian cancer
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Song, Honglin, Dicks, Ed M, Tyrer, Jonathan, Intermaggio, Maria, Chenevix-Trench, Georgia, Bowtell, David D, Traficante, Nadia, Group, AOCS, Brenton, James, Goranova, Teodora, Hosking, Karen, Piskorz, Anna, van Oudenhove, Elke, Doherty, Jen, Harris, Holly R, Rossing, Mary Anne, Duerst, Matthias, Dork, Thilo, Bogdanova, Natalia V, Modugno, Francesmary, Moysich, Kirsten, Odunsi, Kunle, Ness, Roberta, Karlan, Beth Y, Lester, Jenny, Jensen, Allan, Kjaer, Susanne Krüger, Høgdall, Estrid, Campbell, Ian G, Lázaro, Conxi, Pujara, Miguel Angel, Cunningham, Julie, Vierkant, Robert, Winham, Stacey J, Hildebrandt, Michelle, Huff, Chad, Li, Donghui, Wu, Xifeng, Yu, Yao, Permuth, Jennifer B, Levine, Douglas A, Schildkraut, Joellen M, Riggan, Marjorie J, Berchuck, Andrew, Webb, Penelope M, Group, OPAL Study, Cybulski, Cezary, Gronwald, Jacek, Jakubowska, Anna, Lubinski, Jan, Alsop, Jennifer, Harrington, Patricia, Chan, Isaac, Menon, Usha, Pearce, Celeste L, Wu, Anna H, de Fazio, Anna, Kennedy, Catherine J, Goode, Ellen, Ramus, Susan, Gayther, Simon, and Pharoah, Paul
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Biological Sciences ,Biomedical and Clinical Sciences ,Genetics ,Oncology and Carcinogenesis ,Orphan Drug ,Ovarian Cancer ,Prevention ,Clinical Research ,Rare Diseases ,Cancer ,2.1 Biological and endogenous factors ,Aetiology ,Case-Control Studies ,Fanconi Anemia Complementation Group N Protein ,Female ,Genetic Predisposition to Disease ,Genetic Variation ,Humans ,Ovarian Neoplasms ,Risk Assessment ,cancer ,endocrine ,genetic epidemiology ,cancer: endocrine ,Medical and Health Sciences ,Genetics & Heredity ,Clinical sciences - Abstract
PurposeThe known epithelial ovarian cancer (EOC) susceptibility genes account for less than 50% of the heritable risk of ovarian cancer suggesting that other susceptibility genes exist. The aim of this study was to evaluate the contribution to ovarian cancer susceptibility of rare deleterious germline variants in a set of candidate genes.MethodsWe sequenced the coding region of 54 candidate genes in 6385 invasive EOC cases and 6115 controls of broad European ancestry. Genes with an increased frequency of putative deleterious variants in cases versus controls were further examined in an independent set of 14 135 EOC cases and 28 655 controls from the Ovarian Cancer Association Consortium and the UK Biobank. For each gene, we estimated the EOC risks and evaluated associations between germline variant status and clinical characteristics.ResultsThe ORs associated for high-grade serous ovarian cancer were 3.01 for PALB2 (95% CI 1.59 to 5.68; p=0.00068), 1.99 for POLK (95% CI 1.15 to 3.43; p=0.014) and 4.07 for SLX4 (95% CI 1.34 to 12.4; p=0.013). Deleterious mutations in FBXO10 were associated with a reduced risk of disease (OR 0.27, 95% CI 0.07 to 1.00, p=0.049). However, based on the Bayes false discovery probability, only the association for PALB2 in high-grade serous ovarian cancer is likely to represent a true positive.ConclusionsWe have found strong evidence that carriers of PALB2 deleterious mutations are at increased risk of high-grade serous ovarian cancer. Whether the magnitude of risk is sufficiently high to warrant the inclusion of PALB2 in cancer gene panels for ovarian cancer risk testing is unclear; much larger sample sizes will be needed to provide sufficiently precise estimates for clinical counselling.
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- 2021
37. Expanding Our Understanding of Ovarian Cancer Risk: The Role of Incomplete Pregnancies
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Lee, Alice W, Rosenzweig, Stacey, Wiensch, Ashley, Group, the Australian Ovarian Cancer Study, Ramus, Susan J, Menon, Usha, Gentry-Maharaj, Aleksandra, Ziogas, Argyrios, Anton-Culver, Hoda, Whittemore, Alice S, Sieh, Weiva, Rothstein, Joseph H, McGuire, Valerie, Wentzensen, Nicolas, Bandera, Elisa V, Qin, Bo, Terry, Kathryn L, Cramer, Daniel W, Titus, Linda, Schildkraut, Joellen M, Berchuck, Andrew, Goode, Ellen L, Kjaer, Susanne K, Jensen, Allan, Jordan, Susan J, Ness, Roberta B, Modugno, Francesmary, Moysich, Kirsten, Thompson, Pamela J, Goodman, Marc T, Carney, Michael E, Chang-Claude, Jenny, Rossing, Mary Anne, Harris, Holly R, Doherty, Jennifer Anne, Risch, Harvey A, Khoja, Lilah, Alimujiang, Aliya, Phung, Minh Tung, Brieger, Katharine, Mukherjee, Bhramar, Pharoah, Paul DP, Wu, Anna H, Pike, Malcolm C, Webb, Penelope M, and Pearce, Celeste Leigh
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Rare Diseases ,Prevention ,Cancer ,Ovarian Cancer ,Clinical Research ,Aetiology ,2.1 Biological and endogenous factors ,Abortion ,Induced ,Abortion ,Spontaneous ,Carcinoma ,Ovarian Epithelial ,Case-Control Studies ,Female ,Humans ,Ovarian Neoplasms ,Parity ,Pregnancy ,Risk ,United Kingdom ,United States ,Australian Ovarian Cancer Study Group ,Oncology and Carcinogenesis ,Oncology & Carcinogenesis - Abstract
BackgroundParity is associated with decreased risk of invasive ovarian cancer; however, the relationship between incomplete pregnancies and invasive ovarian cancer risk is unclear. This relationship was examined using 15 case-control studies from the Ovarian Cancer Association Consortium (OCAC). Histotype-specific associations, which have not been examined previously with large sample sizes, were also evaluated.MethodsA pooled analysis of 10 470 invasive epithelial ovarian cancer cases and 16 942 controls was conducted. Odds ratios (ORs) and 95% confidence intervals (CIs) for the association between incomplete pregnancies and invasive epithelial ovarian cancer were estimated using logistic regression. All models were conditioned on OCAC study, race and ethnicity, age, and education level and adjusted for number of complete pregnancies, oral contraceptive use, and history of breastfeeding. The same approach was used for histotype-specific analyses.ResultsEver having an incomplete pregnancy was associated with a 16% reduction in ovarian cancer risk (OR = 0.84, 95% CI = 0.79 to 0.89). There was a trend of decreasing risk with increasing number of incomplete pregnancies (2-sided Ptrend < .001). An inverse association was observed for all major histotypes; it was strongest for clear cell ovarian cancer.ConclusionsIncomplete pregnancies are associated with a reduced risk of invasive epithelial ovarian cancer. Pregnancy, including incomplete pregnancy, was associated with a greater reduction in risk of clear cell ovarian cancer, but the result was broadly consistent across histotypes. Future work should focus on understanding the mechanisms underlying this reduced risk.
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- 2021
38. A balancing act: navigating the nuances of co-production in mental health research
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Soklaridis, Sophie, Harris, Holly, Shier, Rowen, Rovet, Jordana, Black, Georgia, Bellissimo, Gail, Gruszecki, Sam, Lin, Elizabeth, and Di Giandomenico, Anna
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- 2024
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39. Prevalence and Characterization of Avoidant Restrictive Food Intake Disorder in a Pediatric Population
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Sader, Michelle, Harris, Holly A., Waiter, Gordon D., Jackson, Margaret C., Voortman, Trudy, Jansen, Pauline W., and Williams, Justin H.G.
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- 2023
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40. Concurrent RB1 Loss and BRCA-Deficiency Predicts Enhanced Immunological Response and Long-Term Survival in Tubo-Ovarian High-Grade Serous Carcinoma
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Saner, Flurina A. M., primary, Takahashi, Kazuaki, additional, Budden, Timothy, additional, Pandey, Ahwan, additional, Ariyaratne, Dinuka, additional, Zwimpfer, Tibor A., additional, Meagher, Nicola S., additional, Fereday, Sian, additional, Twomey, Laura, additional, Pishas, Kathleen I., additional, Hoang, Therese, additional, Bolithon, Adelyn, additional, Traficante, Nadia, additional, Alsop, Kathryn, additional, Christie, Elizabeth L., additional, Kang, Eun-Young, additional, Nelson, Gregg S., additional, Ghatage, Prafull, additional, Lee, Cheng-Han, additional, Riggan, Marjorie J., additional, Alsop, Jennifer, additional, Beckmann, Matthias W., additional, Boros, Jessica, additional, Brand, Alison H., additional, Brooks-Wilson, Angela, additional, Carney, Michael E., additional, Coulson, Penny, additional, Courtney-Brooks, Madeleine, additional, Cushing-Haugen, Kara L., additional, Cybulski, Cezary, additional, El-Bahrawy, Mona, additional, Elishaev, Esther, additional, Erber, Ramona, additional, Gayther, Simon A., additional, Gentry-Maharaj, Aleksandra, additional, Gilks, C. Blake, additional, Harnett, Paul R., additional, Harris, Holly R., additional, Hartmann, Arndt, additional, Hein, Alexander, additional, Hendley, Joy, additional, Hernandez, Brenda Y., additional, Jakubowska, Anna, additional, Jimenez-Linan, Mercedes, additional, Jones, Michael E., additional, Kaufmann, Scott H., additional, Kennedy, Catherine J., additional, Kluz, Tomasz, additional, Koziak, Jennifer M., additional, Kristjansdottir, Björg, additional, Le, Nhu D., additional, Lener, Marcin, additional, Lester, Jenny, additional, Lubiński, Jan, additional, Mateoiu, Constantina, additional, Orsulic, Sandra, additional, Ruebner, Matthias, additional, Schoemaker, Minouk J., additional, Shah, Mitul, additional, Sharma, Raghwa, additional, Sherman, Mark E., additional, Shvetsov, Yurii B., additional, Soong, T. Rinda, additional, Steed, Helen, additional, Sukumvanich, Paniti, additional, Talhouk, Aline, additional, Taylor, Sarah E., additional, Vierkant, Robert A., additional, Wang, Chen, additional, Widschwendter, Martin, additional, Wilkens, Lynne R., additional, Winham, Stacey J., additional, Anglesio, Michael S., additional, Berchuck, Andrew, additional, Brenton, James D., additional, Campbell, Ian, additional, Cook, Linda S., additional, Doherty, Jennifer A., additional, Fasching, Peter A., additional, Fortner, Renée Turzanski., additional, Goodman, Marc T., additional, Gronwald, Jacek, additional, Huntsman, David G., additional, Karlan, Beth Y., additional, Kelemen, Linda E., additional, Menon, Usha, additional, Modugno, Francesmary, additional, Pharoah, Paul D. P., additional, Schildkraut, Joellen M., additional, Sundfeldt, Karin, additional, Swerdlow, Anthony J., additional, Goode, Ellen L., additional, DeFazio, Anna, additional, Köbel, Martin, additional, Ramus, Susan J., additional, Bowtell, David D.L., additional, and Garsed, Dale W., additional
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- 2024
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41. Identifying Subgroups of Toddlers with DSM-5 Autism Spectrum Disorder Based on Core Symptoms
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Harris, Holly K., Lee, Collin, Sideridis, Georgios D., Barbaresi, William J., and Harstad, Elizabeth
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The objective of this study was to identify subgroups of toddlers with DSM-5 ASD based on core ASD symptoms using a person-based analytical framework. This is a retrospective study of 500 toddlers (mean age 26 months, 79% male) with DSM-5 ASD. Data were analyzed using latent class analyses in which profiles were formed based on ASD symptomatology. Social communication (SC) symptoms favored a three-class solution, while restricted/repetitive behaviors (RRBs) favored a two-class solution. Classes with higher consistency of SC deficits were younger, with lower developmental functioning. The class with more RRBs was older, with higher functioning. If confirmed in other populations, these classes may more precisely characterize subgroups within the heterogeneous group of toddlers at time of ASD diagnosis.
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- 2021
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42. Cross-Cancer Genome-Wide Association Study of Endometrial Cancer and Epithelial Ovarian Cancer Identifies Genetic Risk Regions Associated with Risk of Both Cancers
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Glubb, Dylan M, Thompson, Deborah J, Aben, Katja KH, Alsulimani, Ahmad, Amant, Frederic, Annibali, Daniela, Attia, John, Barricarte, Aurelio, Beckmann, Matthias W, Berchuck, Andrew, Bermisheva, Marina, Bernardini, Marcus Q, Bischof, Katharina, Bjorge, Line, Bodelon, Clara, Brand, Alison H, Brenton, James D, Brinton, Louise A, Bruinsma, Fiona, Buchanan, Daniel D, Burghaus, Stefanie, Butzow, Ralf, Cai, Hui, Carney, Michael E, Chanock, Stephen J, Chen, Chu, Chen, Xiao Qing, Chen, Zhihua, Cook, Linda S, Cunningham, Julie M, De Vivo, Immaculata, deFazio, Anna, Doherty, Jennifer A, Dörk, Thilo, du Bois, Andreas, Dunning, Alison M, Dürst, Matthias, Edwards, Todd, Edwards, Robert P, Ekici, Arif B, Ewing, Ailith, Fasching, Peter A, Ferguson, Sarah, Flanagan, James M, Fostira, Florentia, Fountzilas, George, Friedenreich, Christine M, Gao, Bo, Gaudet, Mia M, Gawełko, Jan, Gentry-Maharaj, Aleksandra, Giles, Graham G, Glasspool, Rosalind, Goodman, Marc T, Gronwald, Jacek, Harris, Holly R, Harter, Philipp, Hein, Alexander, Heitz, Florian, Hildebrandt, Michelle AT, Hillemanns, Peter, Høgdall, Estrid, Høgdall, Claus K, Holliday, Elizabeth G, Huntsman, David G, Huzarski, Tomasz, Jakubowska, Anna, Jensen, Allan, Jones, Michael E, Karlan, Beth Y, Karnezis, Anthony, Kelley, Joseph L, Khusnutdinova, Elza, Killeen, Jeffrey L, Kjaer, Susanne K, Klapdor, Rüdiger, Köbel, Martin, Konopka, Bozena, Konstantopoulou, Irene, Kopperud, Reidun K, Koti, Madhuri, Kraft, Peter, Kupryjanczyk, Jolanta, Lambrechts, Diether, Larson, Melissa C, Le Marchand, Loic, Lele, Shashikant, Lester, Jenny, Li, Andrew J, Liang, Dong, Liebrich, Clemens, Lipworth, Loren, Lissowska, Jolanta, Lu, Lingeng, Lu, Karen H, Macciotta, Alessandra, Mattiello, Amalia, May, Taymaa, McAlpine, Jessica N, and McGuire, Valerie
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Epidemiology ,Biomedical and Clinical Sciences ,Health Sciences ,Oncology and Carcinogenesis ,Human Genome ,Uterine Cancer ,Genetics ,Biotechnology ,Ovarian Cancer ,Prevention ,Cancer ,Rare Diseases ,2.1 Biological and endogenous factors ,Aetiology ,Carcinoma ,Ovarian Epithelial ,Endometrial Neoplasms ,Female ,Genome-Wide Association Study ,Humans ,Ovarian Neoplasms ,Quantitative Trait Loci ,Risk Factors ,OPAL Study Group ,AOCS Group ,Medical and Health Sciences ,Biomedical and clinical sciences ,Health sciences - Abstract
BackgroundAccumulating 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.MethodsUsing 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.ResultsGenetic 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 (P Bonferroni < 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.ConclusionsUsing cross-cancer GWAS meta-analysis, we have identified several joint endometrial and ovarian cancer risk loci and candidate target genes for future functional analysis.ImpactOur research highlights the shared genetic relationship between endometrial cancer and ovarian cancer. Further studies in larger sample sets are required to confirm our findings.
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- 2021
43. Development and Validation of the Gene Expression Predictor of High-grade Serous Ovarian Carcinoma Molecular SubTYPE (PrOTYPE)
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Talhouk, Aline, George, Joshy, Wang, Chen, Budden, Timothy, Tan, Tuan Zea, Chiu, Derek S, Kommoss, Stefan, San Leong, Huei, Chen, Stephanie, Intermaggio, Maria P, Gilks, Blake, Nazeran, Tayyebeh M, Volchek, Mila, Elatre, Wafaa, Bentley, Rex C, Senz, Janine, Lum, Amy, Chow, Veronica, Sudderuddin, Hanwei, Mackenzie, Robertson, Leong, Samuel CY, Liu, Geyi, Johnson, Dustin, Chen, Billy, Group, AOCS, Alsop, Jennifer, Banerjee, Susana N, Behrens, Sabine, Bodelon, Clara, Brand, Alison H, Brinton, Louise, Carney, Michael E, Chiew, Yoke-Eng, Cushing-Haugen, Kara L, Cybulski, Cezary, Ennis, Darren, Fereday, Sian, Fortner, Renée T, García-Donas, Jesús, Gentry-Maharaj, Aleksandra, Glasspool, Rosalind, Goranova, Teodora, Greene, Casey S, Haluska, Paul, Harris, Holly R, Hendley, Joy, Hernandez, Brenda Y, Herpel, Esther, Jimenez-Linan, Mercedes, Karpinskyj, Chloe, Kaufmann, Scott H, Keeney, Gary L, Kennedy, Catherine J, Köbel, Martin, Koziak, Jennifer M, Larson, Melissa C, Lester, Jenny, Lewsley, Liz-Anne, Lissowska, Jolanta, Lubiński, Jan, Luk, Hugh, Macintyre, Geoff, Mahner, Sven, McNeish, Iain A, Menkiszak, Janusz, Nevins, Nikilyn, Osorio, Ana, Oszurek, Oleg, Palacios, José, Hinsley, Samantha, Pearce, Celeste L, Pike, Malcolm C, Piskorz, Anna M, Ray-Coquard, Isabelle, Rhenius, Valerie, Rodriguez-Antona, Cristina, Sharma, Raghwa, Sherman, Mark E, De Silva, Dilrini, Singh, Naveena, Sinn, Peter, Slamon, Dennis, Song, Honglin, Steed, Helen, Stronach, Euan A, Thompson, Pamela J, Tołoczko, Aleksandra, Trabert, Britton, Traficante, Nadia, Tseng, Chiu-Chen, Widschwendter, Martin, Wilkens, Lynne R, Winham, Stacey J, Winterhoff, Boris, Beeghly-Fadiel, Alicia, Benitez, Javier, Berchuck, Andrew, Brenton, James D, Brown, Robert, and Chang-Claude, Jenny
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Biomedical and Clinical Sciences ,Oncology and Carcinogenesis ,Biotechnology ,Rare Diseases ,Clinical Research ,Genetics ,Ovarian Cancer ,Cancer ,Clinical Trials and Supportive Activities ,Detection ,screening and diagnosis ,4.2 Evaluation of markers and technologies ,Good Health and Well Being ,Aged ,Algorithms ,Cystadenoma ,Serous ,Female ,Gene Expression Regulation ,Neoplastic ,Humans ,Lymphocytes ,Tumor-Infiltrating ,Middle Aged ,Neoplasm Grading ,Neoplasm Proteins ,Neoplasm ,Residual ,Ovarian Neoplasms ,Transcriptome ,Oncology & Carcinogenesis ,Clinical sciences ,Oncology and carcinogenesis - Abstract
PurposeGene expression-based molecular subtypes of high-grade serous tubo-ovarian cancer (HGSOC), demonstrated across multiple studies, may provide improved stratification for molecularly targeted trials. However, evaluation of clinical utility has been hindered by nonstandardized methods, which are not applicable in a clinical setting. We sought to generate a clinical grade minimal gene set assay for classification of individual tumor specimens into HGSOC subtypes and confirm previously reported subtype-associated features.Experimental designAdopting two independent approaches, we derived and internally validated algorithms for subtype prediction using published gene expression data from 1,650 tumors. We applied resulting models to NanoString data on 3,829 HGSOCs from the Ovarian Tumor Tissue Analysis consortium. We further developed, confirmed, and validated a reduced, minimal gene set predictor, with methods suitable for a single-patient setting.ResultsGene expression data were used to derive the predictor of high-grade serous ovarian carcinoma molecular subtype (PrOTYPE) assay. We established a de facto standard as a consensus of two parallel approaches. PrOTYPE subtypes are significantly associated with age, stage, residual disease, tumor-infiltrating lymphocytes, and outcome. The locked-down clinical grade PrOTYPE test includes a model with 55 genes that predicted gene expression subtype with >95% accuracy that was maintained in all analytic and biological validations.ConclusionsWe validated the PrOTYPE assay following the Institute of Medicine guidelines for the development of omics-based tests. This fully defined and locked-down clinical grade assay will enable trial design with molecular subtype stratification and allow for objective assessment of the predictive value of HGSOC molecular subtypes in precision medicine applications.See related commentary by McMullen et al., p. 5271.
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- 2020
44. Menopausal hormone therapy prior to the diagnosis of ovarian cancer is associated with improved survival
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Brieger, Katharine K, Peterson, Siri, Lee, Alice W, Mukherjee, Bhramar, Bakulski, Kelly M, Alimujiang, Aliya, Anton-Culver, Hoda, Anglesio, Michael S, Bandera, Elisa V, Berchuck, Andrew, Bowtell, David DL, Chenevix-Trench, Georgia, Cho, Kathleen R, Cramer, Daniel W, DeFazio, Anna, Doherty, Jennifer A, Fortner, Renée T, Garsed, Dale W, Gayther, Simon A, Gentry-Maharaj, Aleksandra, Goode, Ellen L, Goodman, Marc T, Harris, Holly R, Høgdall, Estrid, Huntsman, David G, Shen, Hui, Jensen, Allan, Johnatty, Sharon E, Jordan, Susan J, Kjaer, Susanne K, Kupryjanczyk, Jolanta, Lambrechts, Diether, McLean, Karen, Menon, Usha, Modugno, Francesmary, Moysich, Kirsten, Ness, Roberta, Ramus, Susan J, Richardson, Jean, Risch, Harvey, Rossing, Mary Anne, Trabert, Britton, Wentzensen, Nicolas, Ziogas, Argyrios, Terry, Kathryn L, Wu, Anna H, Hanley, Gillian E, Pharoah, Paul, Webb, Penelope M, Pike, Malcolm C, Pearce, Celeste Leigh, and Consortium, for the Ovarian Cancer Association
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Biomedical and Clinical Sciences ,Oncology and Carcinogenesis ,Estrogen ,Rare Diseases ,Cancer ,Ovarian Cancer ,Aging ,Aged ,Estrogen Replacement Therapy ,Female ,Hormone Replacement Therapy ,Humans ,Middle Aged ,Neoplasm Staging ,Neoplasm ,Residual ,Ovarian Neoplasms ,Postmenopause ,Progestins ,Progression-Free Survival ,Proportional Hazards Models ,Survival Rate ,Ovarian Cancer Association Consortium ,Paediatrics and Reproductive Medicine ,Oncology & Carcinogenesis ,Clinical sciences ,Oncology and carcinogenesis ,Reproductive medicine - Abstract
PurposePrior studies of menopausal hormone therapy (MHT) and ovarian cancer survival have been limited by lack of hormone regimen detail and insufficient sample sizes. To address these limitations, a comprehensive analysis of 6419 post-menopausal women with pathologically confirmed ovarian carcinoma was conducted to examine the association between MHT use prior to diagnosis and survival.MethodsData from 15 studies in the Ovarian Cancer Association Consortium were included. MHT use was examined by type (estrogen-only (ET) or estrogen+progestin (EPT)), duration, and recency of use relative to diagnosis. Cox proportional hazards models were used to estimate the association between hormone therapy use and survival. Logistic regression and mediation analysis was used to explore the relationship between MHT use and residual disease following debulking surgery.ResultsUse of ET or EPT for at least five years prior to diagnosis was associated with better ovarian cancer survival (hazard ratio, 0.80; 95% CI, 0.74 to 0.87). Among women with advanced stage, high-grade serous carcinoma, those who used MHT were less likely to have any macroscopic residual disease at the time of primary debulking surgery (p for trend
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- 2020
45. Racial differences in the association of body mass index and ovarian cancer risk in the OCWAA Consortium
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Ochs-Balcom, Heather M., Johnson, Courtney, Guertin, Kristin A., Qin, Bo, Beeghly-Fadiel, Alicia, Camacho, Fabian, Bethea, Traci N., Dempsey, Lauren F., Rosenow, Will, Joslin, Charlotte E., Myers, Evan, Moorman, Patricia G., Harris, Holly R., Peres, Lauren C., Wendy Setiawan, V., Wu, Anna H., Rosenberg, Lynn, Schildkraut, Joellen M., and Bandera, Elisa V.
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- 2022
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46. Pre-diagnosis and post-diagnosis dietary patterns and survival in women with ovarian cancer
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Sasamoto, Naoko, Wang, Tianyi, Townsend, Mary K., Eliassen, A. Heather, Tabung, Fred K., Giovannucci, Edward L., Matulonis, Ursula A., Terry, Kathryn L., Tworoger, Shelley S., and Harris, Holly R.
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- 2022
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47. Cannabis smoking, tobacco cigarette smoking, and adenomyosis risk
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Joachim, Grace E., Bohnert, Kipling M., As-Sanie, Sawsan, Harris, Holly R., and Upson, Kristen
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- 2023
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48. Cross-cancer genome-wide association study of endometrial cancer and epithelial ovarian cancer identifies genetic risk regions associated with risk of both cancers
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Glubb, Dylan M, Thompson, Deborah J, Aben, Katja KH, Alsulimani, Ahmad, Amant, Frederic, Annibali, Daniela, Attia, John, Barricarte, Aurelio, Beckmann, Matthias W, Berchuck, Andrew, Bermisheva, Marina, Bernardini, Marcus Q, Bischof, Katharina, Bjorge, Line, Bodelon, Clara, Brand, Alison H, Brenton, James D, Brinton, Louise, Bruinsma, Fiona, Buchanan, Daniel D, Burghaus, Stefanie, Butzow, Ralf, Cai, Hui, Carney, Michael E, Chanock, Stephen J, Chen, Chu, Chen, Xiao Qing, Chen, Zhihua, Cook, Linda S, Cunningham, Julie M, De Vivo, Immaculata, deFazio, Anna, Doherty, Jennifer A, Dörk, Thilo, du Bois, Andreas, Dunning, Alison M, Dürst, Matthias, Edwards, Todd, Edwards, Robert P, Ekici, Arif B, Ewing, Ailith, Fasching, Peter A, Ferguson, Sarah, Flanagan, James M, Fostira, Florentia, Fountzilas, George, Friedenreich, Christine M, Gao, Bo, Gaudet, Mia M, Gawełko, Jan, Gentry-Maharaj, Aleksandra, Giles, Graham G, Glasspool, Rosalind, Goodman, Marc T, Gronwald, Jacek, Group, OPAL Study, Group, AOCS, Harris, Holly R, Harter, Philipp, Hein, Alexander, Heitz, Florian, Hildebrandt, Michelle AT, Hillemanns, Peter, Høgdall, Estrid, Høgdall, Claus K, Holliday, Elizabeth G, Huntsman, David G, Huzarski, Tomasz, Jakubowska, Anna, Jensen, Allan, Jones, Michael E, Karlan, Beth Y, Karnezis, Anthony, Kelley, Joseph L, Khusnutdinova, Elza, Killeen, Jeffrey L, Kjaer, Susanne K, Klapdor, Rüdiger, Köbel, Martin, Konopka, Bozena, Konstantopoulou, Irene, Kopperud, Reidun K, Koti, Madhuri, Kraft, Peter, Kupryjanczyk, Jolanta, Lambrechts, Diether, Larson, Melissa C, Le Marchand, Loic, Lele, Shashikant B, Lester, Jenny, Li, Andrew J, Liang, Dong, Liebrich, Clemens, Lipworth, Loren, Lissowska, Jolanta, Lu, Lingeng, Lu, Karen H, Macciotta, Alessandra, Mattiello, Amalia, and May, Taymaa
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Biological Sciences ,Biomedical and Clinical Sciences ,Genetics ,Epidemiology ,Health Sciences ,Statistics ,Mathematical Sciences ,Oncology and Carcinogenesis ,Aging ,Rare Diseases ,Human Genome ,Cancer ,Uterine Cancer ,Ovarian Cancer ,Prevention ,Biotechnology ,Aetiology ,2.1 Biological and endogenous factors - Abstract
Abstract: Accumulating evidence suggests a relationship between endometrial cancer and epithelial ovarian cancer. For example, endometrial cancer and epithelial ovarian cancer share epidemiological risk factors and molecular features observed across histotypes are held in common (e.g. serous, endometrioid and clear cell). Independent genome-wide association studies (GWAS) for endometrial cancer and epithelial ovarian cancer have identified 16 and 27 risk regions, respectively, four of which overlap between the two cancers. Using GWAS summary statistics, we explored the shared genetic etiology between endometrial cancer and epithelial ovarian cancer. Genetic correlation analysis using LD Score regression revealed significant genetic correlation between the two cancers (rG = 0.43, P = 2.66 × 10−5). To identify loci associated with the risk of both cancers, we implemented a pipeline of statistical genetic analyses (i.e. inverse-variance meta-analysis, co-localization, and M-values), and performed analyses by stratified by subtype. We found seven loci associated with risk for both cancers (PBonferroni < 2.4 × 10−9). In addition, four novel regions at 7p22.2, 7q22.1, 9p12 and 11q13.3 were identified at a sub-genome wide threshold (P < 5 × 10−7). Integration with promoter-associated HiChIP chromatin loops from immortalized endometrium and epithelial ovarian cell lines, and expression quantitative trait loci (eQTL) data highlighted candidate target genes for further investigation.
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- 2020
49. Population based targeted sequencing of 54 candidate genes identifies PALB2 as a susceptibility gene for high grade serous ovarian cancer
- Author
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Song, Honglin, Dicks, Ed, Tyrer, Jonathan P, Intermaggio, Maria, Chenevix-Trench, Georgia, Bowtell, David D, Traficante, Nadia, Group, AOCS, Brenton, James D, Goranova, Teodora, Hosking, Karen, Piskorz, Anna, Van Oudenhove, Elke, Doherty, Jennifer Anne, Harris, Holly R, Rossing, Mary Anne, Dürst, Matthias, Dörk, Thilo, Bogdanova, Natalia V, Modugno, Francesmary, Moysich, Kirsten B, Odunsi, Kunle, Ness, Roberta B, Karlan, Beth Y, Lester, Jenny, Jensen, Allan, Kjaer, Susanne K, Høgdall, Estrid, Campbell, Ian, Lazaro, Conxi, Pujana, Miquel Angel, Cunningham, Julie M, Vierkant, Robert A, Winham, Stacey J, Hildebrandt, Michelle AT, Huff, Chad, Li, Donghui, Wu, Xifeng, Yu, Yao, Permuth, Jennifer B, Levine, Douglas A, Schildkraut, Joellen M, Riggan, Marjorie J, Berchuck, Andrew, Webb, Penelope M, Group, OPAL Study, Cybulski, Cezary, Gronwald, Jacek, Jakubowska, Anna, Lubiński, Jan, Alsop, Jennifer, Harrington, Patricia A, Chan, Isaac, Menon, Usha, Pearce, Celeste L, Wu, Anna H, de Fazio, Anna, Kennedy, Catherine J, Goode, Ellen L, Ramus, Susan J, Gayther, Simon A, and Pharoah, Paul DP
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Biological Sciences ,Biomedical and Clinical Sciences ,Genetics ,Health Sciences ,Oncology and Carcinogenesis ,Orphan Drug ,Clinical Research ,Human Genome ,Rare Diseases ,Ovarian Cancer ,Cancer ,Prevention ,2.1 Biological and endogenous factors ,Aetiology - Abstract
Abstract: Purpose: The known EOC susceptibility genes account for less than 50% of the heritable risk of ovarian cancer suggesting other susceptibility genes exist. The aim of this study was to evaluate the contribution to ovarian cancer susceptibility of rare deleterious germline variants in a set of candidate genes. Methods: We sequenced the coding region of 54 candidate genes in 6385 invasive EOC cases and 6115 controls of broad European ancestry. Genes with an increased frequency of putative deleterious variants in cases verses controls were further examined in an independent set of 14,146 EOC cases and 28,661 controls from the ovarian cancer association consortium and the UK Biobank. For each gene, we estimated the EOC risks and evaluated associations between germline variant status and clinical characteristics. Results: The odds ratios (OR) associated for high-grade serous ovarian cancer were 3.01 for PALB2 (95% CI 1.59 – 5.68; P = 0.00068), 1.99 for POLK (95% CI 1.15 – 3.43; P = 0.014), and 4.07 for SLX4 (95% CI 1.34-12.4; P = 0.013). Deleterious mutations in FBXO10 were associated with a reduced risk of disease (OR 0.27, 95% CI 0.07 −1.00, P=0.049). However, based on the Bayes false discovery probability, only the association for PALB2 in high-grade serous ovarian cancer is likely to represent a true positive. Conclusions: We have found strong evidence that carriers of PALB2 deleterious mutations are at increased risk of high-grade serous ovarian cancer. Whether the magnitude of risk is sufficiently high to warrant the inclusion of PALB2 in cancer gene panels for ovarian cancer risk testing is unclear; much larger sample sizes will be needed to provide sufficiently precise estimates for clinical counselling.
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- 2019
50. Circulating androgens and postmenopausal ovarian cancer risk in the Women's Health Initiative Observational Study
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Trabert, Britton, Michels, Kara A, Anderson, Garnet L, Brinton, Louise A, Falk, Roni T, Geczik, Ashley M, Harris, Holly R, Pan, Kathy, Pfeiffer, Ruth M, Qi, Lihong, Rohan, Thomas, Wentzensen, Nicolas, and Xu, Xia
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Estrogen ,Clinical Research ,Rare Diseases ,Cancer ,Ovarian Cancer ,Aging ,2.1 Biological and endogenous factors ,Aetiology ,Aged ,Androgens ,Androsterone ,Case-Control Studies ,Chromatography ,Liquid ,Female ,Glucuronides ,Humans ,Logistic Models ,Middle Aged ,Ovarian Neoplasms ,Postmenopause ,Risk Factors ,Tandem Mass Spectrometry ,Women's Health ,endogenous androgens ,androgen metabolites ,androgenic activity ,ovarian cancer risk ,nested case-control study ,heterogeneity ,Oncology and Carcinogenesis ,Oncology & Carcinogenesis - Abstract
Our knowledge of epidemiologic risk factors for ovarian cancer supports a role for androgens in the pathogenesis of this disease; however, few studies have examined associations between circulating androgens and ovarian cancer risk. Using highly sensitive LC-MS/MS assays, we evaluated associations between pre-diagnostic serum levels of 12 androgens, including novel androgen metabolites that reflect androgen activity in tissues, and ovarian cancer risk among postmenopausal women in a nested case-control study in the Women's Health Initiative (WHI) Observational Study (OS). We frequency-matched 169 ovarian cancer cases to 410 controls from women enrolled in WHI-OS who were not using menopausal hormones at enrollment/blood draw. We estimated associations overall and by subtype (n = 102 serous/67 non-serous) using multivariable adjusted logistic regression. Androgen/androgen metabolite levels were not associated with overall ovarian cancer risk. In analyses by subtype, women with increased levels of androsterone-glucuronide (ADT-G) and total 5-α reduced glucuronide metabolites (markers of tissue-level androgenic activity) were at increased risk of developing non-serous ovarian cancer: ADT-G tertile (T)3 versus T1 odds ratio [OR] (95% confidence interval [CI]) 4.36 (1.68-11.32), p-heterogeneity 0.002; total glucuronide metabolites 3.63 (1.47-8.95), 0.002. Risk of developing serous tumors was unrelated to these markers. ADT-G and total glucuronide metabolites, better markers of tissue-level androgenic activity in women than testosterone, were associated with an increased risk of developing non-serous ovarian cancer. Our work demonstrates that sex steroid metabolism is important in the etiology of non-serous ovarian cancers and supports a heterogeneous hormonal etiology across histologic subtypes of ovarian cancer.
- Published
- 2019
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