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17 results on '"Viduka, S."'

1. Prognostic gene expression signature for high-grade serous ovarian cancer

Author

Millstein, J, Budden, T, Goode, EL, Anglesio, MS, Talhouk, A, Intermaggio, MP, Leong, HS, Chen, S, Elatre, W, Gilks, B, Nazeran, T, Volchek, M, Bentley, RC, Wang, C, Chiu, DS, Kommoss, S, Leung, SCY, Senz, J, Lum, A, Chow, V, Sudderuddin, H, Mackenzie, R, George, J, Group, AOCS, Bowtell, D, Chenevix-Trench, G, Green, A, Webb, P, DeFazio, A, Gertig, D, Traficante, N, Fereday, S, Moore, S, Hung, J, Harrap, K, Sadkowsky, T, Pandeya, N, Malt, M, Mellon, A, Robertson, R, Bergh, T Vanden, Jones, M, Mackenzie, P, Maidens, J, Nattress, K, Chiew, YE, Stenlake, A, Sullivan, H, Alexander, B, Ashover, P, Brown, S, Corrish, T, Green, L, Jackman, L, Ferguson, K, Martin, K, Martyn, A, Ranieri, B, White, J, Jayde, V, Mamers, P, Bowes, L, Galletta, L, Giles, D, Hendley, J, Alsop, K, Schmidt, T, Shirley, H, Ball, C, Young, C, Viduka, S, Tran, Hoa, Bilic, Sanela, Glavinas, Lydia, Brooks, Julia, Stuart-Harris, R, Kirsten, F, Rutovitz, J, Clingan, P, Glasgow, A, Proietto, A, Braye, S, Otton, G, Shannon, J, Bonaventura, T, Stewart, J, Begbie, S, Friedlander, M, Bell, D, Baron-Hay, S, Ferrier, AA, Gard, G, Nevell, D, Pavlakis, N, Valmadre, S, Young, B, Camaris, C, Crouch, R, Edwards, L, and Hacker, N

Subjects
Biomedical and Clinical Sciences, Oncology and Carcinogenesis, Women's Health, Ovarian Cancer, Cancer, Human Genome, Orphan Drug, Genetic Testing, Rare Diseases, Precision Medicine, Genetics, 4.4 Population screening, 4.1 Discovery and preclinical testing of markers and technologies, 5.1 Pharmaceuticals, Cystadenocarcinoma, Serous, Female, Humans, Ovarian Neoplasms, Prognosis, Proportional Hazards Models, Survival Analysis, Transcriptome, formalin-fixed paraffin-embedded, gene expression, high-grade serous ovarian cancer, overall survival, prognosis, AOCS Group, Oncology & Carcinogenesis, Clinical sciences, Oncology and carcinogenesis
Abstract

BackgroundMedian overall survival (OS) for women with high-grade serous ovarian cancer (HGSOC) is ∼4 years, yet survival varies widely between patients. There are no well-established, gene expression signatures associated with prognosis. The aim of this study was to develop a robust prognostic signature for OS in patients with HGSOC.Patients and methodsExpression of 513 genes, selected from a meta-analysis of 1455 tumours and other candidates, was measured using NanoString technology from formalin-fixed paraffin-embedded tumour tissue collected from 3769 women with HGSOC from multiple studies. Elastic net regularization for survival analysis was applied to develop a prognostic model for 5-year OS, trained on 2702 tumours from 15 studies and evaluated on an independent set of 1067 tumours from six studies.ResultsExpression levels of 276 genes were associated with OS (false discovery rate < 0.05) in covariate-adjusted single-gene analyses. The top five genes were TAP1, ZFHX4, CXCL9, FBN1 and PTGER3 (P < 0.001). The best performing prognostic signature included 101 genes enriched in pathways with treatment implications. Each gain of one standard deviation in the gene expression score conferred a greater than twofold increase in risk of death [hazard ratio (HR) 2.35, 95% confidence interval (CI) 2.02-2.71; P < 0.001]. Median survival [HR (95% CI)] by gene expression score quintile was 9.5 (8.3 to -), 5.4 (4.6-7.0), 3.8 (3.3-4.6), 3.2 (2.9-3.7) and 2.3 (2.1-2.6) years.ConclusionThe OTTA-SPOT (Ovarian Tumor Tissue Analysis consortium - Stratified Prognosis of Ovarian Tumours) gene expression signature may improve risk stratification in clinical trials by identifying patients who are least likely to achieve 5-year survival. The identified novel genes associated with the outcome may also yield opportunities for the development of targeted therapeutic approaches.

Published
2020

2. MyD88 and TLR4 Expression in Epithelial Ovarian Cancer

Author

Block, Matthew S, Vierkant, Robert A, Rambau, Peter F, Winham, Stacey J, Wagner, Philipp, Traficante, Nadia, Tołoczko, Aleksandra, Tiezzi, Daniel G, Taran, Florin Andrei, Sinn, Peter, Sieh, Weiva, Sharma, Raghwa, Rothstein, Joseph H, Ramón y Cajal, Teresa, Paz-Ares, Luis, Oszurek, Oleg, Orsulic, Sandra, Ness, Roberta B, Nelson, Gregg, Modugno, Francesmary, Menkiszak, Janusz, McGuire, Valerie, McCauley, Bryan M, Mack, Marie, Lubiński, Jan, Longacre, Teri A, Li, Zheng, Lester, Jenny, Kennedy, Catherine J, Kalli, Kimberly R, Jung, Audrey Y, Johnatty, Sharon E, Jimenez-Linan, Mercedes, Jensen, Allan, Intermaggio, Maria P, Hung, Jillian, Herpel, Esther, Hernandez, Brenda Y, Hartkopf, Andreas D, Harnett, Paul R, Ghatage, Prafull, García-Bueno, José M, Gao, Bo, Fereday, Sian, Eilber, Ursula, Edwards, Robert P, de Sousa, Christiani B, de Andrade, Jurandyr M, Chudecka-Głaz, Anita, Chenevix-Trench, Georgia, Cazorla, Alicia, Brucker, Sara Y, Group, Australian Ovarian Cancer Study, Bowtell, D, Chenevix-Trench, G, Green, A, Webb, P, DeFazio, A, Gertig, D, Traficante, N, Fereday, S, Moore, S, Hung, J, Harrap, K, Sadkowsky, T, Pandeya, N, Malt, M, Mellon, A, Robertson, R, Bergh, T Vanden, Jones, M, Mackenzie, P, Maidens, J, Nattress, K, Chiew, YE, Stenlake, A, Sullivan, H, Alexander, B, Ashover, P, Brown, S, Corrish, T, Green, L, Jackman, L, Ferguson, K, Martin, K, Martyn, A, Ranieri, B, White, J, Jayde, V, Mamers, P, Bowes, L, Galletta, L, Giles, D, Hendley, J, Alsop, K, Schmidt, T, Shirley, H, Ball, C, Young, C, and Viduka, S

Subjects
Biomedical and Clinical Sciences, Oncology and Carcinogenesis, Rare Diseases, Ovarian Cancer, Cancer, Women's Health, Clinical Research, 5.1 Pharmaceuticals, Adult, Aged, Biomarkers, Tumor, Carcinoma, Ovarian Epithelial, Female, Humans, Immunohistochemistry, Middle Aged, Myeloid Differentiation Factor 88, Ovarian Neoplasms, Survival Analysis, Tissue Array Analysis, Toll-Like Receptor 4, Australian Ovarian Cancer Study Group, Medical and Health Sciences, Biomedical and clinical sciences
Abstract

ObjectiveTo evaluate myeloid differentiation primary response gene 88 (MyD88) and Toll-like receptor 4 (TLR4) expression in relation to clinical features of epithelial ovarian cancer, histologic subtypes, and overall survival.Patients and methodsWe conducted centralized immunohistochemical staining, semi-quantitative scoring, and survival analysis in 5263 patients participating in the Ovarian Tumor Tissue Analysis consortium. Patients were diagnosed between January 1, 1978, and December 31, 2014, including 2865 high-grade serous ovarian carcinomas (HGSOCs), with more than 12,000 person-years of follow-up time. Tissue microarrays were stained for MyD88 and TLR4, and staining intensity was classified using a 2-tiered system for each marker (weak vs strong).ResultsExpression of MyD88 and TLR4 was similar in all histotypes except clear cell ovarian cancer, which showed reduced expression compared with other histotypes (P

Published
2018

3. Refined cut-off for TP53 immunohistochemistry improves prediction of TP53 mutation status in ovarian mucinous tumors: implications for outcome analyses

Author

Kang, Eun Young, Cheasley, Dane, LePage, Cecile, Wakefield, Matthew J., da Cunha Torres, Michelle, Rowley, Simone, Salazar, Carolina, Xing, Zhongyue, Allan, Prue, Bowtell, David D.L., Mes-Masson, Anne-Marie, Provencher, Diane M., Rahimi, Kurosh, Kelemen, Linda E., Fasching, Peter A., Doherty, Jennifer A., Goodman, Marc T., Goode, Ellen L., Deen, Suha, Pharoah, Paul D.P., Brenton, James D., Sieh, Weiva, Mateoiu, Constantina, Sundfeldt, Karin, Cook, Linda S., Le, Nhu D., Anglesio, Michael S., Gilks, C. Blake, Huntsman, David G., Kennedy, Catherine J., Traficante, Nadia, Bowtell, D., Chenevix-Trench, G., Green, A., Webb, P., DeFazio, A., Gertig, D., Traficante, N., Fereday, S., Moore, S., Hung, J., Harrap, K., Sadkowsky, T., Pandeya, N., Malt, M., Mellon, A., Robertson, R., Bergh, T. Vanden, Jones, M., Mackenzie, P., Maidens, J., Nattress, K., Chiew, Y.E., Stenlake, A., Sullivan, H., Alexander, B., Ashover, P., Brown, S., Corrish, T., Green, L., Jackman, L., Ferguson, K., Martin, K., Martyn, A., Ranieri, B., White, J., Jayde, V., Mamers, P., Bowes, L., Galletta, L., Giles, D., Hendley, J., Alsop, K., Schmidt, T., Shirley, H., Ball, C., Young, C., Viduka, S., Tran, Hoa, Bilic, Sanela, Glavinas, Lydia, Brooks, Julia, Stuart-Harris, R., Kirsten, F., Rutovitz, J., Clingan, P., Glasgow, A., Proietto, A., Braye, S., Otton, G., Shannon, J., Bonaventura, T., Stewart, J., Begbie, S., Friedlander, M., Bell, D., Baron-Hay, S., Ferrier, A., Gard, G., Nevell, D., Pavlakis, N., Valmadre, S., Young, B., Camaris, C., Crouch, R., Edwards, L., Hacker, N., Marsden, D., Robertson, G., Beale, P., Beith, J., Carter, J., Dalrymple, C., Houghton, R., Russell, P., Links, M., Grygiel, J., Hill, J., Brand, A., Byth, K., Jaworski, R., Harnett, P., Sharma, R., Wain, G., Ward, B., Papadimos, D., Crandon, A., Cummings, M., Horwood, K., Obermair, A., Perrin, L., Wyld, D., Nicklin, J., Davy, M., Oehler, M.K., Hall, C., Dodd, T., Healy, T., Pittman, K., Henderson, D., Miller, J., Pierdes, J., Blomfield, P., Challis, D., McIntosh, R., Parker, A., Brown, B., Rome, R., Allen, D., Grant, P., Hyde, S., Laurie, R., Robbie, M., Healy, D., Jobling, T., Manolitsas, T., McNealage, J., Rogers, P., Susil, B., Sumithran, E., Simpson, I., Phillips, K., Rischin, D., Fox, S., Johnson, D., Lade, S., Loughrey, M., O'Callaghan, N., Murray, W., Waring, P., Billson, V., Pyman, J., Neesham, D., Quinn, M., Underhill, C., Bell, R., Ng, L.F., Blum, R., Ganju, V., Hammond, I., Leung, Y., McCartney, A., Buck, M., Haviv, I., Purdie, D., Whiteman, D., Zeps, N., DeFazio, Anna, Kaufmann, Scott, Churchman, Michael, Gourley, Charlie, Stephens, Andrew N., Meagher, Nicola S., Ramus, Susan J., Antill, Yoland C., Campbell, Ian, Scott, Clare L., Köbel, Martin, Gorringe, Kylie L., Ryland, Georgina L., Allan, Prue E., Alsop, Kathryn, Ananda, Sumitra, Au-Yeung, George, Böhm, Maret, Brand, Alison, Chenevix-Trench, Georgia, Christie, Michael, Chiew, Yoke-Eng, Dudley, Rhiannon, Fairweather, Nicole, Fereday, Sian, Fox, Stephen B., Hacker, Neville F., Hadley, Alison M., Hendley, Joy, Ho, Gwo-Yaw, Hunter, Sally M., Jobling, Tom W., Kalli, Kimberly R., Kaufmann, Scott H., Le Page, Cecile, McNally, Orla M., McAlpine, Jessica N., Mileshkin, Linda, Pyman, Jan, Samimi, Goli, Sharma, Ragwha, and Campbell, Ian G.

Published
2021
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4. Prognostic gene expression signature for high-grade serous ovarian cancer

Author

Bowtell, D., Chenevix-Trench, G., Green, A., Webb, P., DeFazio, A., Gertig, D., Traficante, N., Fereday, S., Moore, S., Hung, J., Harrap, K., Sadkowsky, T., Pandeya, N., Malt, M., Mellon, A., Robertson, R., Vanden Bergh, T., Jones, M., Mackenzie, P., Maidens, J., Nattress, K., Chiew, Y.E., Stenlake, A., Sullivan, H., Alexander, B., Ashover, P., Brown, S., Corrish, T., Green, L., Jackman, L., Ferguson, K., Martin, K., Martyn, A., Ranieri, B., White, J., Jayde, V., Mamers, P., Bowes, L., Galletta, L., Giles, D., Hendley, J., Alsop, K., Schmidt, T., Shirley, H., Ball, C., Young, C., Viduka, S., Tran, Hoa, Bilic, Sanela, Glavinas, Lydia, Brooks, Julia, Stuart-Harris, R., Kirsten, F., Rutovitz, J., Clingan, P., Glasgow, A., Proietto, A., Braye, S., Otton, G., Shannon, J., Bonaventura, T., Stewart, J., Begbie, S., Friedlander, M., Bell, D., Baron-Hay, S., Ferrier,a, A., Gard, G., Nevell, D., Pavlakis, N., Valmadre, S., Young, B., Camaris, C., Crouch, R., Edwards, L., Hacker, N., Marsden, D., Robertson, G., Beale, P., Beith, J., Carter, J., Dalrymple, C., Houghton, R., Russell, P., Links, M., Grygiel, J., Hill, J., Brand, A., Byth, K., Jaworski, R., Harnett, P., Sharma, R., Wain, G., Ward, B., Papadimos, D., Crandon, A., Cummings, M., Horwood, K., Obermair, A., Perrin, L., Wyld, D., Nicklin, J., Davy, M., Oehler, M.K., Hall, C., Dodd, T., Healy, T., Pittman, K., Henderson, D., Miller, J., Pierdes, J., Blomfield, P., Challis, D., McIntosh, R., Parker, A., Brown, B., Rome, R., Allen, D., Grant, P., Hyde, S., Laurie, R., Robbie, M., Healy, D., Jobling, T., Manolitsas, T., McNealage, J., Rogers, P., Susil, B., Sumithran, E., Simpson, I., Phillips, K., Rischin, D., Fox, S., Johnson, D., Lade, S., Loughrey, M., O’Callaghan, N., Murray, W., Waring, P., Billson, V., Pyman, J., Neesham, D., Quinn, M., Underhill, C., Bell, R., Ng, L.F., Blum, R., Ganju, V., Hammond, I., Leung, Y., McCartney, A., Buck, M., Haviv, I., Purdie, D., Whiteman, D., Zeps, N., Millstein, J., Budden, T., Goode, E.L., Anglesio, M.S., Talhouk, A., Intermaggio, M.P., Leong, H.S., Chen, S., Elatre, W., Gilks, B., Nazeran, T., Volchek, M., Bentley, R.C., Wang, C., Chiu, D.S., Kommoss, S., Leung, S.C.Y., Senz, J., Lum, A., Chow, V., Sudderuddin, H., Mackenzie, R., George, J., Steed, H., Koziak, J.M., Köbel, M., McNeish, I.A., Goranova, T., Ennis, D., Macintyre, G., Silva De Silva, D., Ramón y Cajal, T., García-Donas, J., Hernando Polo, S., Rodriguez, G.C., Cushing-Haugen, K.L., Harris, H.R., Greene, C.S., Zelaya, R.A., Behrens, S., Fortner, R.T., Sinn, P., Herpel, E., Lester, J., Lubiński, J., Oszurek, O., Tołoczko, A., Cybulski, C., Menkiszak, J., Pearce, C.L., Pike, M.C., Tseng, C., Alsop, J., Rhenius, V., Song, H., Jimenez-Linan, M., Piskorz, A.M., Gentry-Maharaj, A., Karpinskyj, C., Widschwendter, M., Singh, N., Kennedy, C.J., Harnett, P.R., Gao, B., Johnatty, S.E., Sayer, R., Boros, J., Winham, S.J., Keeney, G.L., Kaufmann, S.H., Larson, M.C., Luk, H., Hernandez, B.Y., Thompson, P.J., Wilkens, L.R., Carney, M.E., Trabert, B., Lissowska, J., Brinton, L., Sherman, M.E., Bodelon, C., Hinsley, S., Lewsley, L.A., Glasspool, R., Banerjee, S.N., Stronach, E.A., Haluska, P., Ray-Coquard, I., Mahner, S., Winterhoff, B., Slamon, D., Levine, D.A., Kelemen, L.E., Benitez, J., Chang-Claude, J., Gronwald, J., Wu, A.H., Menon, U., Goodman, M.T., Schildkraut, J.M., Wentzensen, N., Brown, R., Berchuck, A., deFazio, A., Gayther, S.A., García, M.J., Henderson, M.J., Rossing, M.A., Beeghly-Fadiel, A., Fasching, P.A., Orsulic, S., Karlan, B.Y., Konecny, G.E., Huntsman, D.G., Bowtell, D.D., Brenton, J.D., Doherty, J.A., Pharoah, P.D.P., and Ramus, S.J.

Published
2020
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5. MyD88 and TLR4 Expression in Epithelial Ovarian Cancer

Author

Bowtell, D., Chenevix-Trench, G., Green, A., Webb, P., DeFazio, A., Gertig, D., Traficante, N., Fereday, S., Moore, S., Hung, J., Harrap, K., Sadkowsky, T., Pandeya, N., Malt, M., Mellon, A., Robertson, R., Vanden Bergh, T., Jones, M., Mackenzie, P., Maidens, J., Nattress, K., Chiew, Y.E., Stenlake, A., Sullivan, H., Alexander, B., Ashover, P., Brown, S., Corrish, T., Green, L., Jackman, L., Ferguson, K., Martin, K., Martyn, A., Ranieri, B., White, J., Jayde, V., Mamers, P., Bowes, L., Galletta, L., Giles, D., Hendley, J., Alsop, K., Schmidt, T., Shirley, H., Ball, C., Young, C., Viduka, S., Tran, Hoa, Bilic, Sanela, Glavinas, Lydia, Brooks, Julia, Stuart-Harris, R., Kirsten, F., Rutovitz, J., Clingan, P., Glasgow, A., Proietto, A., Braye, S., Otton, G., Shannon, J., Bonaventura, T., Stewart, J., Begbie, S., Friedlander, M., Bell, D., Baron-Hay, S., Ferrier, A., Gard, G., Nevell, D., Pavlakis, N., Valmadre, S., Young, B., Camaris, C., Crouch, R., Edwards, L., Hacker, N., Marsden, D., Robertson, G., Beale, P., Beith, J., Carter, J., Dalrymple, C., Houghton, R., Russell, P., Links, M., Grygiel, J., Hill, J., Brand, A., Byth, K., Jaworski, R., Harnett, P., Sharma, R., Wain, G., Ward, B., Papadimos, D., Crandon, A., Cummings, M., Horwood, K., Obermair, A., Perrin, L., Wyld, D., Nicklin, J., Davy, M., Oehler, M.K., Hall, C., Dodd, T., Healy, T., Pittman, K., Henderson, D., Miller, J., Pierdes, J., Blomfield, P., Challis, D., McIntosh, R., Parker, A., Brown, B., Rome, R., Allen, D., Grant, P., Hyde, S., Laurie, R., Robbie, M., Healy, D., Jobling, T., Manolitsas, T., McNealage, J., Rogers, P., Susil, B., Sumithran, E., Simpson, I., Phillips, K., Rischin, D., Fox, S., Johnson, D., Lade, S., Loughrey, M., O'Callaghan, N., Murray, W., Waring, P., Billson, V., Pyman, J., Neesham, D., Quinn, M., Underhill, C., Bell, R., Ng, L.F., Blum, R., Ganju, V., Hammond, I., Leung, Y., McCartney, A., Buck, M., Haviv, I., Purdie, D., Whiteman, D., Zeps, N., Block, Matthew S., Vierkant, Robert A., Rambau, Peter F., Winham, Stacey J., Wagner, Philipp, Traficante, Nadia, Tołoczko, Aleksandra, Tiezzi, Daniel G., Taran, Florin Andrei, Sinn, Peter, Sieh, Weiva, Sharma, Raghwa, Rothstein, Joseph H., Ramón y Cajal, Teresa, Paz-Ares, Luis, Oszurek, Oleg, Orsulic, Sandra, Ness, Roberta B., Nelson, Gregg, Modugno, Francesmary, Menkiszak, Janusz, McGuire, Valerie, McCauley, Bryan M., Mack, Marie, Lubiński, Jan, Longacre, Teri A., Li, Zheng, Lester, Jenny, Kennedy, Catherine J., Kalli, Kimberly R., Jung, Audrey Y., Johnatty, Sharon E., Jimenez-Linan, Mercedes, Jensen, Allan, Intermaggio, Maria P., Hung, Jillian, Herpel, Esther, Hernandez, Brenda Y., Hartkopf, Andreas D., Harnett, Paul R., Ghatage, Prafull, García-Bueno, José M., Gao, Bo, Fereday, Sian, Eilber, Ursula, Edwards, Robert P., de Sousa, Christiani B., de Andrade, Jurandyr M., Chudecka-Głaz, Anita, Chenevix-Trench, Georgia, Cazorla, Alicia, Brucker, Sara Y., Alsop, Jennifer, Whittemore, Alice S., Steed, Helen, Staebler, Annette, Moysich, Kirsten B., Menon, Usha, Koziak, Jennifer M., Kommoss, Stefan, Kjaer, Susanne K., Kelemen, Linda E., Karlan, Beth Y., Huntsman, David G., Høgdall, Estrid, Gronwald, Jacek, Goodman, Marc T., Gilks, Blake, García, María José, Fasching, Peter A., de Fazio, Anna, Deen, Suha, Chang-Claude, Jenny, Candido dos Reis, Francisco J., Campbell, Ian G., Brenton, James D., Bowtell, David D., Benítez, Javier, Pharoah, Paul D.P., Köbel, Martin, Ramus, Susan J., and Goode, Ellen L.

Published
2018
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6. Copy Number Variants Are Ovarian Cancer Risk Alleles at Known and Novel Risk Loci

Author

Devries, Amber A, Dennis, Joe, Tyrer, Jonathan P, Peng, Pei-chen, Coetzee, Simon G, Reyes, Alberto L, Plummer, Jasmine T, Davis, Brian D, Chen, Stephanie S, Dezem, Felipe Segato, Aben, Katja K H, Anton-culver, Hoda, Antonenkova, Natalia N, Beckmann, Matthias W, Beeghly-fadiel, Alicia, Berchuck, Andrew, Bogdanova, Natalia V, Bogdanova-markov, Nadja, Brenton, James D, Butzow, Ralf, Campbell, Ian, Chang-claude, Jenny, Chenevix-trench, G, Cook, Linda S, Defazio, A, Doherty, Jennifer A, Dörk, Thilo, Eccles, Diana M, Eliassen, A Heather, Fasching, Peter A, Fortner, Renée T, Giles, Graham G, Goode, Ellen L, Goodman, Marc T, Gronwald, Jacek, Webb, P, Friedlander, M, Obermair, A, Grant, P, Nagle, C, Beesley, V, Chevenix-trench, G, Bowtell, D, Blomfield, P, Brand, A, Davis, A, Leung, Y, Nicklin, J, Quinn, M, Livingstone, K, O'neill, H, Williams, M, Black, A, Hadley, A, Glasgow, A, Garrett, A, Rao, A, Shannon, C, Steer, C, Allen, D, Neesham, D, Otton, G, Au-yeung, G, Goss, G, Wain, G, Gard, G, Robertson, G, Lombard, J, Tan, J, Mcneilage, J, Power, J, Coward, J, Miller, J, Carter, J, Lamont, J, Wong, K M, Reid, K, Perrin, L, Milishkin, L, Nascimento, M, Buck, M, Bunting, M, Harrison, M, Chetty, N, Hacker, N, Mcnally, O, Harnett, P, Beale, P, Awad, R, Mohan, R, Farrell, R, Mcintosh, R, Rome, R, Sayer, R, Houghton, R, Hogg, R, Land, R, Baron-hay, S, Paramasivum, S, Pather, S, Hyde, S, Salfinger, S, Valmadre, S, Jobling, T, Manolitsas, T, Bonaventura, T, Arora, V, Green, A, Gertig, D, Traficante, N, Fereday, S, Moore, S, Hung, J, Harrap, K, Sadkowsky, T, Pandeya, N, Malt, M, Robertson, R, Bergh, T Vanden, Jones, M, Mckenzie, P, Maidens, J, Nattress, K, Chiew, Y E, Stenlake, A, Sullivan, H, Alexander, B, Ashover, P, Brown, S, Corrish, T, Green, L, Jackman, L, Ferguson, K, Martin, K, Martyn, A, Ranieri, B, White, J, Jayde, V, Bowes, L, Mamers, P, Galletta, L, Giles, D, Hendley, J, Alsop, K, Schmidt, T, Shirley, H, Ball, C, Young, C, Viduka, S, Tran, H, Bilic, S, Glavinas, L, Brooks, J, Stuart-harris, R, Kirsten, F, Rutovitz, J, Clingan, P, Proietto, A, Braye, S, Shannon, J, Stewart, J, Begbie, S, Håkansson, Niclas, Hildebrandt, Michelle A T, Huff, Chad, Huntsman, David G, Jensen, Allan, Kar, Siddhartha, Karlan, Beth Y, Khusnutdinova, Elza K, Kiemeney, Lambertus A, Kjaer, Susanne K, Kupryjanczyk, Jolanta, Labrie, Marilyne, Lambrechts, Diether, Le, Nhu D, Lubiński, Jan, May, Taymaa, Menon, Usha, Milne, Roger L, Modugno, Francesmary, Monteiro, Alvaro N, Moysich, Kirsten B, Odunsi, Kunle, Olsson, Håkan, Pearce, Celeste L, Pejovic, Tanja, Ramus, Susan J, Riboli, Elio, Riggan, Marjorie J, Romieu, Isabelle, Sandler, Dale P, Schildkraut, Joellen M, Setiawan, V Wendy, Sieh, Weiva, Song, Honglin, Sutphen, Rebecca, Terry, Kathryn L, Thompson, Pamela J, Titus, Linda, Tworoger, Shelley S, Van Nieuwenhuysen, Els, Edwards, Digna Velez, Webb, Penelope M, Wentzensen, Nicolas, Whittemore, Alice S, Wolk, Alicja, Wu, Anna H, Ziogas, Argyrios, Freedman, Matthew L, Lawrenson, Kate, Pharoah, Paul D P, Easton, Douglas F, Gayther, Simon A, Jones, Michelle R, Helsinki University Hospital Area, Clinicum, Department of Pathology, and HUSLAB

Subjects
Cancer Research, GENES, DNA Copy Number Variations, SUSCEPTIBILITY LOCI, 3122 Cancers, Carcinoma, Ovarian Epithelial, Polymorphism, Single Nucleotide, BREAST, Humans, Genetic Predisposition to Disease, BRCA2 MUTATIONS, GENOME-WIDE ASSOCIATION, Alleles, Ovarian Neoplasms, Cancer och onkologi, Science & Technology, IDENTIFICATION, REARRANGEMENTS, COMMON VARIANTS, GERMLINE MUTATIONS, DELETIONS, Oncology, Urological cancers Radboud Institute for Health Sciences [Radboudumc 15], Cancer and Oncology, Female, Life Sciences & Biomedicine, Genome-Wide Association Study
Abstract

Background Known risk alleles for epithelial ovarian cancer (EOC) account for approximately 40% of the heritability for EOC. Copy number variants (CNVs) have not been investigated as EOC risk alleles in a large population cohort. Methods Single nucleotide polymorphism array data from 13 071 EOC cases and 17 306 controls of White European ancestry were used to identify CNVs associated with EOC risk using a rare admixture maximum likelihood test for gene burden and a by-probe ratio test. We performed enrichment analysis of CNVs at known EOC risk loci and functional biofeatures in ovarian cancer–related cell types. Results We identified statistically significant risk associations with CNVs at known EOC risk genes; BRCA1 (PEOC = 1.60E-21; OREOC = 8.24), RAD51C (Phigh-grade serous ovarian cancer [HGSOC] = 5.5E-4; odds ratio [OR]HGSOC = 5.74 del), and BRCA2 (PHGSOC = 7.0E-4; ORHGSOC = 3.31 deletion). Four suggestive associations (P Conclusions CNVs in BRCA1 have been previously reported in smaller studies, but their observed frequency in this large population-based cohort, along with the CNVs observed at BRCA2 and RAD51C gene loci in EOC cases, suggests that these CNVs are potentially pathogenic and may contribute to the spectrum of disease-causing mutations in these genes. CNVs are likely to occur in a wider set of susceptibility regions, with potential implications for clinical genetic testing and disease prevention.

Published
2022
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7. Refined cut-off for TP53 immunohistochemistry improves prediction of TP53 mutation status in ovarian mucinous tumors: implications for outcome analyses.

Author

Friedlander M., Russell P., Links M., Grygiel J., Hill J., Byth K., Jaworski R., Harnett P., Wain G., Ward B., Papadimos D., Crandon A., Cummings M., Horwood K., Obermair A., Perrin L., Wyld D., Nicklin J., Davy M., Oehler M.K., Hall C., Dodd T., Healy T., Pittman K., Henderson D., Miller J., Pierdes J., Blomfield P., Challis D., McIntosh R., Parker A., Brown B., Rome R., Allen D., Grant P., Hyde S., Laurie R., Robbie M., Healy D., Jobling T., Manolitsas T., McNealage J., Rogers P., Susil B., Sumithran E., Simpson I., Phillips K., Rischin D., Fox S., Johnson D., Lade S., Loughrey M., O'Callaghan N., Murray W., Waring P., Billson V., Pyman J., Neesham D., Quinn M., Underhill C., Bell R., Ng L.F., Blum R., Ganju V., Hammond I., Leung Y., McCartney A., Buck M., Haviv I., Purdie D., Whiteman D., Zeps N., Kaufmann S., Meagher N.S., Ramus S.J., Campbell I., Cheasley D., Wakefield M.J., Ryland G.L., Allan P.E., Alsop K., Ananda S., Anglesio M.S., Au-Yeung G., Bohm M., Bowtell D.D.L., Brand A., Chenevix-Trench G., Christie M., Chiew Y.-E., Churchman M., DeFazio A., Dudley R., Fairweather N., Fereday S., Fox S.B., Gilks C.B., Gourley C., Hacker N.F., Hadley A.M., Hendley J., Ho G.-Y., Huntsman D.G., Hunter S.M., Jobling T.W., Kalli K.R., Kaufmann S.H., Kennedy C.J., Kobel M., Le Page C., McNally O.M., McAlpine J.N., Mileshkin L., Jan Pyman, Rahimi K., Samimi G., Sharma R., Stephens A.N., Traficante N., Antill Y.C., Scott C.L., Campbell I.G., Gorringe K.L., Kang E.Y., LePage C., da Cunha Torres M., Rowley S., Salazar C., Xing Z., Allan P., Mes-Masson A.-M., Provencher D.M., Kelemen L.E., Fasching P.A., Doherty J.A., Goodman M.T., Goode E.L., Deen S., Pharoah P.D.P., Brenton J.D., Sieh W., Mateoiu C., Sundfeldt K., Cook L.S., Le N.D., Bowtell D., Green A., Webb P., Gertig D., Moore S., Hung J., Harrap K., Sadkowsky T., Pandeya N., Malt M., Mellon A., Robertson R., Bergh T.V., Jones M., Mackenzie P., Maidens J., Nattress K., Chiew Y.E., Stenlake A., Sullivan H., Alexander B., Ashover P., Brown S., Corrish T., Green L., Jackman L., Ferguson K., Martin K., Martyn A., Ranieri B., White J., Jayde V., Mamers P., Bowes L., Galletta L., Giles D., Schmidt T., Shirley H., Ball C., Young C., Viduka S., Tran H., Bilic S., Glavinas L., Brooks J., Stuart-Harris R., Kirsten F., Rutovitz J., Clingan P., Glasgow A., Proietto A., Braye S., Otton G., Shannon J., Bonaventura T., Stewart J., Begbie S., Bell D., Baron-Hay S., Ferrier A., Gard G., Nevell D., Pavlakis N., Valmadre S., Young B., Camaris C., Crouch R., Edwards L., Hacker N., Marsden D., Robertson G., Beale P., Beith J., Carter J., Dalrymple C., Houghton R., Friedlander M., Russell P., Links M., Grygiel J., Hill J., Byth K., Jaworski R., Harnett P., Wain G., Ward B., Papadimos D., Crandon A., Cummings M., Horwood K., Obermair A., Perrin L., Wyld D., Nicklin J., Davy M., Oehler M.K., Hall C., Dodd T., Healy T., Pittman K., Henderson D., Miller J., Pierdes J., Blomfield P., Challis D., McIntosh R., Parker A., Brown B., Rome R., Allen D., Grant P., Hyde S., Laurie R., Robbie M., Healy D., Jobling T., Manolitsas T., McNealage J., Rogers P., Susil B., Sumithran E., Simpson I., Phillips K., Rischin D., Fox S., Johnson D., Lade S., Loughrey M., O'Callaghan N., Murray W., Waring P., Billson V., Pyman J., Neesham D., Quinn M., Underhill C., Bell R., Ng L.F., Blum R., Ganju V., Hammond I., Leung Y., McCartney A., Buck M., Haviv I., Purdie D., Whiteman D., Zeps N., Kaufmann S., Meagher N.S., Ramus S.J., Campbell I., Cheasley D., Wakefield M.J., Ryland G.L., Allan P.E., Alsop K., Ananda S., Anglesio M.S., Au-Yeung G., Bohm M., Bowtell D.D.L., Brand A., Chenevix-Trench G., Christie M., Chiew Y.-E., Churchman M., DeFazio A., Dudley R., Fairweather N., Fereday S., Fox S.B., Gilks C.B., Gourley C., Hacker N.F., Hadley A.M., Hendley J., Ho G.-Y., Huntsman D.G., Hunter S.M., Jobling T.W., Kalli K.R., Kaufmann S.H., Kennedy C.J., Kobel M., Le Page C., McNally O.M., McAlpine J.N., Mileshkin L., Jan Pyman, Rahimi K., Samimi G., Sharma R., Stephens A.N., Traficante N., Antill Y.C., Scott C.L., Campbell I.G., Gorringe K.L., Kang E.Y., LePage C., da Cunha Torres M., Rowley S., Salazar C., Xing Z., Allan P., Mes-Masson A.-M., Provencher D.M., Kelemen L.E., Fasching P.A., Doherty J.A., Goodman M.T., Goode E.L., Deen S., Pharoah P.D.P., Brenton J.D., Sieh W., Mateoiu C., Sundfeldt K., Cook L.S., Le N.D., Bowtell D., Green A., Webb P., Gertig D., Moore S., Hung J., Harrap K., Sadkowsky T., Pandeya N., Malt M., Mellon A., Robertson R., Bergh T.V., Jones M., Mackenzie P., Maidens J., Nattress K., Chiew Y.E., Stenlake A., Sullivan H., Alexander B., Ashover P., Brown S., Corrish T., Green L., Jackman L., Ferguson K., Martin K., Martyn A., Ranieri B., White J., Jayde V., Mamers P., Bowes L., Galletta L., Giles D., Schmidt T., Shirley H., Ball C., Young C., Viduka S., Tran H., Bilic S., Glavinas L., Brooks J., Stuart-Harris R., Kirsten F., Rutovitz J., Clingan P., Glasgow A., Proietto A., Braye S., Otton G., Shannon J., Bonaventura T., Stewart J., Begbie S., Bell D., Baron-Hay S., Ferrier A., Gard G., Nevell D., Pavlakis N., Valmadre S., Young B., Camaris C., Crouch R., Edwards L., Hacker N., Marsden D., Robertson G., Beale P., Beith J., Carter J., Dalrymple C., and Houghton R.

Abstract

TP53 mutations are implicated in the progression of mucinous borderline tumors (MBOT) to mucinous ovarian carcinomas (MOC). Optimized immunohistochemistry (IHC) for TP53 has been established as a proxy for the TP53 mutation status in other ovarian tumor types. We aimed to confirm the ability of TP53 IHC to predict TP53 mutation status in ovarian mucinous tumors and to evaluate the association of TP53 mutation status with survival among patients with MBOT and MOC. Tumor tissue from an initial cohort of 113 women with MBOT/MOC was stained with optimized IHC for TP53 using tissue microarrays (75.2%) or full sections (24.8%) and interpreted using established criteria as normal or abnormal (overexpression, complete absence, or cytoplasmic). Cases were considered concordant if abnormal IHC staining predicted deleterious TP53 mutations. Discordant tissue microarray cases were re-evaluated on full sections and interpretational criteria were refined. The initial cohort was expanded to a total of 165 MBOT and 424 MOC for the examination of the association of survival with TP53 mutation status, assessed either by TP53 IHC and/or sequencing. Initially, 82/113 (72.6%) cases were concordant using the established criteria. Refined criteria for overexpression to account for intratumoral heterogeneity and terminal differentiation improved concordance to 93.8% (106/113). In the expanded cohort, 19.4% (32/165) of MBOT showed evidence for TP53 mutation and this was associated with a higher risk of recurrence, disease-specific death, and all-cause mortality (overall survival: HR = 4.6, 95% CI 1.5-14.3, p = 0.0087). Within MOC, 61.1% (259/424) harbored a TP53 mutation, but this was not associated with survival (overall survival, p = 0.77). TP53 IHC is an accurate proxy for TP53 mutation status with refined interpretation criteria accounting for intratumoral heterogeneity and terminal differentiation in ovarian mucinous tumors. TP53 mutation status is an important biomarker to identify MB

Published
2021

8. BRAF mutations in low-grade serous ovarian cancer and response to BRAF inhibition.

Author

Jones M., Patch A.-M., Alsop K., Ball C., Young C., Schmidt T., Shirley H., Viduka S., Bilic S., Glavinas L., Brooks J., Traficante N., Stuart-Harris R., Kirsten F., Rutovitz J., Clingan P., Glasgow A., Valmadre S., Young B., Camaris C., Crouch R., Edwards L., Hacker N., Marsden D., Robertson G., Beale P., Beith J., Carter J., Dalrymple C., Houghton R., Russell P., Links M., Grygiel J., Hill J., Brand A., Byth K., Jaworski R., Sharma R., Harnett P., Wain G., Friedlander M., Ward B., Papadimos D., Crandon A., Cummings M., Horwood K., Obermair A., Perrin L., Wyld D., Nicklin J., Davy M., Oehler M.K., Hall C., Dodd T., Healy T., Pittman K., Henderson D., Miller J., Pierdes J., Blomfield P., Challis D., McIntosh R., Parker A., Brown B., Rome R., Allen D., Grant P., Hyde S., Laurie R., Robbie M., Healy D., Manolitsas T., McNealage J., Rogers P., Susil B., Sumithran E., Simpson I., Phillips K., Rischin D., Fox S., Johnson D., Lade S., Loughrey M., O'Callaghan N., Murray W., Waring P., Billson V., Pyman J., Neesham D., Quinn M., Underhill C., Ng L.F., Blum R., Ganju V., Hammond I., Leung Y., McCartney A., Buck M., Haviv I., Purdie D., Whiteman D., Zeps N., Bell R., Jobling T., Tran H., Moujaber T., Etemadmoghadam D., Kennedy C.J., Chiew Y.E., Balleine R.L., Saunders C., Wain G.V., Gao B., Hogg R., Srirangan S., Kan C., Fereday S., Pearson J.V., Waddell N., Grimmond S.M., Dobrovic A., Bowtell D.D.L., Harnett P.R., deFazio A., Bowtell D., Chenevix-Trench G., Green A., Webb P., Gertig D., Moore S., Harrap K., Sadkowsky T., Pandeya N., Hung J., Malt M., Alexander B., Ashover P., Brown S., Corrish T., Green L., Jackman L., Ferguson K., Martin K., Martyn A., Ranieri B., Mellon A., Robertson R., Vanden Bergh T., Mackenzie P., Maidens J., Nattress K., Stenlake A., Sullivan H., White J., Jayde V., Mamers P., Bowes L., Galletta L., Giles D., Hendley J., Proietto A., Braye S., Otton G., Shannon J., Bonaventura T., Stewart J., Begbie S., Bell D., Baron-Hay S., Ferrier A., Gard G., Nevell D., Pavlakis N., Jones M., Patch A.-M., Alsop K., Ball C., Young C., Schmidt T., Shirley H., Viduka S., Bilic S., Glavinas L., Brooks J., Traficante N., Stuart-Harris R., Kirsten F., Rutovitz J., Clingan P., Glasgow A., Valmadre S., Young B., Camaris C., Crouch R., Edwards L., Hacker N., Marsden D., Robertson G., Beale P., Beith J., Carter J., Dalrymple C., Houghton R., Russell P., Links M., Grygiel J., Hill J., Brand A., Byth K., Jaworski R., Sharma R., Harnett P., Wain G., Friedlander M., Ward B., Papadimos D., Crandon A., Cummings M., Horwood K., Obermair A., Perrin L., Wyld D., Nicklin J., Davy M., Oehler M.K., Hall C., Dodd T., Healy T., Pittman K., Henderson D., Miller J., Pierdes J., Blomfield P., Challis D., McIntosh R., Parker A., Brown B., Rome R., Allen D., Grant P., Hyde S., Laurie R., Robbie M., Healy D., Manolitsas T., McNealage J., Rogers P., Susil B., Sumithran E., Simpson I., Phillips K., Rischin D., Fox S., Johnson D., Lade S., Loughrey M., O'Callaghan N., Murray W., Waring P., Billson V., Pyman J., Neesham D., Quinn M., Underhill C., Ng L.F., Blum R., Ganju V., Hammond I., Leung Y., McCartney A., Buck M., Haviv I., Purdie D., Whiteman D., Zeps N., Bell R., Jobling T., Tran H., Moujaber T., Etemadmoghadam D., Kennedy C.J., Chiew Y.E., Balleine R.L., Saunders C., Wain G.V., Gao B., Hogg R., Srirangan S., Kan C., Fereday S., Pearson J.V., Waddell N., Grimmond S.M., Dobrovic A., Bowtell D.D.L., Harnett P.R., deFazio A., Bowtell D., Chenevix-Trench G., Green A., Webb P., Gertig D., Moore S., Harrap K., Sadkowsky T., Pandeya N., Hung J., Malt M., Alexander B., Ashover P., Brown S., Corrish T., Green L., Jackman L., Ferguson K., Martin K., Martyn A., Ranieri B., Mellon A., Robertson R., Vanden Bergh T., Mackenzie P., Maidens J., Nattress K., Stenlake A., Sullivan H., White J., Jayde V., Mamers P., Bowes L., Galletta L., Giles D., Hendley J., Proietto A., Braye S., Otton G., Shannon J., Bonaventura T., Stewart J., Begbie S., Bell D., Baron-Hay S., Ferrier A., Gard G., Nevell D., and Pavlakis N.

Abstract

Purpose Low-grade serous ovarian carcinoma (LGSC) responds poorly to chemotherapy and is characterized by activating mutations in the Ras sarcoma-mitogen-activated protein kinase (RAS-MAPK) pathway, including oncogenic BRAF. However, response to BRAF inhibitors is tumor-type specific. Significant improvement in survival is seen in patients with BRAF-mutant melanoma, but other cancer types, such as colorectal cancers, are generally less sensitive. We examined the frequency and characteristics of BRAF-mutated LGSC and described the response to treatment with BRAF inhibitors. Patients and Methods Mutations were assessed in LGSC (N = 65) by using targeted, exome, and whole-genome sequencing. Patient characteristics, treatment, and clinical outcome were assessed, and the median follow-up time was more than 5 years. BRAF inhibitors were trialed in two patients with a somatic BRAF V600E mutation: one patient received dabrafenib monotherapy and was monitored clinically, biochemically (cancer antigen [CA]-125 levels), and with positron emission tomography (PET) imaging. Expression of the BRAF V600E protein in this patient was assessed by immunohistochemistry. Results Among patients with LGSC, nine (13.8%) of 65 had a somatic BRAF mutation. Of the nine patients with BRAF mutation-positive LGSC, four experienced progressive disease that did not respond to conventional chemotherapy. Two of the patients experienced progression quickly and died as a result of disease progression, and two received targeted treatment. Two patients with BRAF V600E mutation received BRAF inhibitors at relapse and both achieved durable responses. Conclusion BRAF mutations are not uncommon in patients with LGSC and should be routinely tested, because BRAF inhibitors can be an effective treatment for these patients. The results highlight the need for targeted treatment in this rare tumor type, and a prospective study is needed to formally assess the response rate and clinical benefit.Copyright © 2019 Am

Published
2019

9. Methylation of all BRCA1 copies predicts response to the PARP inhibitor rucaparib in ovarian carcinoma.

Author

Jones M., Ferguson K., Martin K., Martyn A., Ranieri B., White J., Jayde V., Mamers P., Bowes L., Giles D., Hendley J., Schmidt T., Shirley H., Ball C., Young C., Viduka S., Tran H., Bilic S., Glavinas L., Brooks J., Stuart-Harris R., Kirsten F., Rutovitz J., Brand A., Byth K., Jaworski R., Harnett P., Sharma R., Wain G., Ward B., Papadimos D., Crandon A., Cummings M., Horwood K., Obermair A., Perrin L., Wyld D., Nicklin J., Davy M., Oehler M.K., Hall C., Dodd T., Healy T., Pittman K., Henderson D., Miller J., Pierdes J., Blomfield P., Challis D., McIntosh R., Parker A., Brown B., Rome R., Allen D., Grant P., Hyde S., Laurie R., Robbie M., Healy D., Manolitsas T., McNealage J., Rogers P., Susil B., Sumithran E., Simpson I., Phillips K., Rischin D., Fox S., Johnson D., Lade S., Loughrey M., O'Callaghan N., Murray W., Waring P., Billson V., Pyman J., Neesham D., Quinn M., Underhill C., Ng L.F., Blum R., Ganju V., Hammond I., Leung Y., McCartney A., Buck M., Haviv I., Purdie D., Whiteman D., Zeps N., deFazio A., McNeish I.A., Bowtell D.D., Swisher E.M., Dobrovic A., Wakefield M.J., Scott C.L., Bell R., Jobling T., Kondrashova O., Topp M., Nesic K., Lieschke E., Ho G.-Y., Harrell M.I., Zapparoli G.V., Hadley A., Holian R., Boehm E., Heong V., Sanij E., Pearson R.B., Krais J.J., Johnson N., McNally O., Ananda S., Alsop K., Hutt K.J., Kaufmann S.H., Lin K.K., Harding T.C., Traficante N., Chenevix-Trench G., Green A., Webb P., Gertig D., Fereday S., Moore S., Hung J., Harrap K., Sadkowsky T., Pandeya N., Malt M., Mellon A., Robertson R., VandenBergh T., Mackenzie P., Maidens J., Nattress K., Chiew Y.E., Stenlake A., Sullivan H., Alexander B., Ashover P., Brown S., Corrish T., Green L., Jackman L., Galletta L., Clingan P., Glasgow A., Proietto A., Braye S., Otton G., Shannon J., Bonaventura T., Stewart J., Begbie S., Friedlander M., Bell D., Baron-Hay S., Ferrier A., Gard G., Nevell D., Pavlakis N., Valmadre S., Young B., Camaris C., Crouch R., Edwards L., Hacker N., Marsden D., Robertson G., Beale P., Beith J., Carter J., Dalrymple C., Houghton R., Russell P., Links M., Grygiel J., Hill J., Jones M., Ferguson K., Martin K., Martyn A., Ranieri B., White J., Jayde V., Mamers P., Bowes L., Giles D., Hendley J., Schmidt T., Shirley H., Ball C., Young C., Viduka S., Tran H., Bilic S., Glavinas L., Brooks J., Stuart-Harris R., Kirsten F., Rutovitz J., Brand A., Byth K., Jaworski R., Harnett P., Sharma R., Wain G., Ward B., Papadimos D., Crandon A., Cummings M., Horwood K., Obermair A., Perrin L., Wyld D., Nicklin J., Davy M., Oehler M.K., Hall C., Dodd T., Healy T., Pittman K., Henderson D., Miller J., Pierdes J., Blomfield P., Challis D., McIntosh R., Parker A., Brown B., Rome R., Allen D., Grant P., Hyde S., Laurie R., Robbie M., Healy D., Manolitsas T., McNealage J., Rogers P., Susil B., Sumithran E., Simpson I., Phillips K., Rischin D., Fox S., Johnson D., Lade S., Loughrey M., O'Callaghan N., Murray W., Waring P., Billson V., Pyman J., Neesham D., Quinn M., Underhill C., Ng L.F., Blum R., Ganju V., Hammond I., Leung Y., McCartney A., Buck M., Haviv I., Purdie D., Whiteman D., Zeps N., deFazio A., McNeish I.A., Bowtell D.D., Swisher E.M., Dobrovic A., Wakefield M.J., Scott C.L., Bell R., Jobling T., Kondrashova O., Topp M., Nesic K., Lieschke E., Ho G.-Y., Harrell M.I., Zapparoli G.V., Hadley A., Holian R., Boehm E., Heong V., Sanij E., Pearson R.B., Krais J.J., Johnson N., McNally O., Ananda S., Alsop K., Hutt K.J., Kaufmann S.H., Lin K.K., Harding T.C., Traficante N., Chenevix-Trench G., Green A., Webb P., Gertig D., Fereday S., Moore S., Hung J., Harrap K., Sadkowsky T., Pandeya N., Malt M., Mellon A., Robertson R., VandenBergh T., Mackenzie P., Maidens J., Nattress K., Chiew Y.E., Stenlake A., Sullivan H., Alexander B., Ashover P., Brown S., Corrish T., Green L., Jackman L., Galletta L., Clingan P., Glasgow A., Proietto A., Braye S., Otton G., Shannon J., Bonaventura T., Stewart J., Begbie S., Friedlander M., Bell D., Baron-Hay S., Ferrier A., Gard G., Nevell D., Pavlakis N., Valmadre S., Young B., Camaris C., Crouch R., Edwards L., Hacker N., Marsden D., Robertson G., Beale P., Beith J., Carter J., Dalrymple C., Houghton R., Russell P., Links M., Grygiel J., and Hill J.

Abstract

Accurately identifying patients with high-grade serous ovarian carcinoma (HGSOC) who respond to poly(ADP-ribose) polymerase inhibitor (PARPi) therapy is of great clinical importance. Here we show that quantitative BRCA1 methylation analysis provides new insight into PARPi response in preclinical models and ovarian cancer patients. The response of 12 HGSOC patient-derived xenografts (PDX) to the PARPi rucaparib was assessed, with variable dose-dependent responses observed in chemo-naive BRCA1/2-mutated PDX, and no responses in PDX lacking DNA repair pathway defects. Among BRCA1-methylated PDX, silencing of all BRCA1 copies predicts rucaparib response, whilst heterozygous methylation is associated with resistance. Analysis of 21 BRCA1-methylated platinum-sensitive recurrent HGSOC (ARIEL2 Part 1 trial) confirmed that homozygous or hemizygous BRCA1 methylation predicts rucaparib clinical response, and that methylation loss can occur after exposure to chemotherapy. Accordingly, quantitative BRCA1 methylation analysis in a pre-treatment biopsy could allow identification of patients most likely to benefit, and facilitate tailoring of PARPi therapy.Copyright © 2018, The Author(s).

Published
2018

10. Methylation of all BRCA1 copies predicts response to the PARP inhibitor rucaparib in ovarian carcinoma

Author

Kondrashova, O, Topp, M, Nesic, K, Lieschke, E, Ho, G-Y, Harrell, M, Zapparoli, G, Hadley, A, Holian, R, Boehm, E, Heong, V, Sanij, E, Pearson, RB, Krais, JJ, Johnson, N, McNally, O, Ananda, S, Alsop, K, Hutt, KJ, Kaufmann, SH, Lin, KK, Harding, TC, Traficante, N, deFazio, A, McNeish, LA, Bowtell, DD, Swisher, EM, Dobrovic, A, Wakefield, MJ, Scott, CL, Chenevix-Trench, G, Green, A, Webb, P, Gertig, D, Fereday, S, Moore, S, Hung, J, Harrap, K, Sadkowsky, T, Pandeya, N, Malt, M, Mellon, A, Robertson, R, Vanden Bergh, T, Jones, M, Mackenzie, P, Maidens, J, Nattress, K, Chiew, YE, Stenlake, A, Sullivan, H, Alexander, B, Ashover, P, Brown, S, Corrish, T, Green, L, Jackman, L, Ferguson, K, Martin, K, Martyn, A, Ranieri, B, White, J, Jayde, V, Mamers, P, Bowes, L, Galletta, L, Giles, D, Hendley, J, Schmidt, T, Shirley, H, Ball, C, Young, C, Viduka, S, Tran, H, Bilic, S, Glavinas, L, Brooks, J, Stuart-Harris, R, Kirsten, F, Rutovitz, J, Clingan, P, Glasgow, A, Proietto, A, Braye, S, Otton, G, Shannon, J, Bonaventura, T, Stewart, J, Begbie, S, Friedlander, M, Bell, D, Baron-Hay, S, Ferrier, A, Gard, G, Nevell, D, Pavlakis, N, Valmadre, S, Young, B, Camaris, C, Crouch, R, Edwards, L, Hacker, N, Marsden, D, Robertson, G, Beale, P, Beith, J, Carter, J, Dalrymple, C, Houghton, R, Russell, P, Links, M, Grygiel, J, Hill, J, Brand, A, Byth, K, Jaworski, R, Harnett, P, Sharma, R, Wain, G, Ward, B, Papadimos, D, Crandon, A, Cummings, M, Horwood, K, Obermair, A, Perrin, L, Wyld, D, Nicklin, J, Davy, M, Oehler, MK, Hall, C, Dodd, T, Healy, T, Pittman, K, Henderson, D, Miller, J, Pierdes, J, Blomfield, P, Challis, D, Mclntosh, R, Parker, A, Brown, B, Rome, R, Allen, D, Grant, P, Hyde, S, Laurie, R, Robbie, M, Healy, D, Jobling, T, Manolitsas, T, McNealage, J, Rogers, P, Susil, B, Sumithran, E, Simpson, I, Phillips, K, Rischin, D, Fox, S, Johnson, D, Lade, S, Loughrey, M, O'Callaghan, N, Murray, W, Waring, P, Billson, V, Pyman, J, Neesham, D, Quinn, M, Underhill, C, Bell, R, Ng, LF, Blum, R, Ganju, V, Hammond, I, Leung, Y, McCartney, A, Buck, M, Haviv, I, Purdie, D, Whiteman, D, Zeps, N, Kondrashova, O, Topp, M, Nesic, K, Lieschke, E, Ho, G-Y, Harrell, M, Zapparoli, G, Hadley, A, Holian, R, Boehm, E, Heong, V, Sanij, E, Pearson, RB, Krais, JJ, Johnson, N, McNally, O, Ananda, S, Alsop, K, Hutt, KJ, Kaufmann, SH, Lin, KK, Harding, TC, Traficante, N, deFazio, A, McNeish, LA, Bowtell, DD, Swisher, EM, Dobrovic, A, Wakefield, MJ, Scott, CL, Chenevix-Trench, G, Green, A, Webb, P, Gertig, D, Fereday, S, Moore, S, Hung, J, Harrap, K, Sadkowsky, T, Pandeya, N, Malt, M, Mellon, A, Robertson, R, Vanden Bergh, T, Jones, M, Mackenzie, P, Maidens, J, Nattress, K, Chiew, YE, Stenlake, A, Sullivan, H, Alexander, B, Ashover, P, Brown, S, Corrish, T, Green, L, Jackman, L, Ferguson, K, Martin, K, Martyn, A, Ranieri, B, White, J, Jayde, V, Mamers, P, Bowes, L, Galletta, L, Giles, D, Hendley, J, Schmidt, T, Shirley, H, Ball, C, Young, C, Viduka, S, Tran, H, Bilic, S, Glavinas, L, Brooks, J, Stuart-Harris, R, Kirsten, F, Rutovitz, J, Clingan, P, Glasgow, A, Proietto, A, Braye, S, Otton, G, Shannon, J, Bonaventura, T, Stewart, J, Begbie, S, Friedlander, M, Bell, D, Baron-Hay, S, Ferrier, A, Gard, G, Nevell, D, Pavlakis, N, Valmadre, S, Young, B, Camaris, C, Crouch, R, Edwards, L, Hacker, N, Marsden, D, Robertson, G, Beale, P, Beith, J, Carter, J, Dalrymple, C, Houghton, R, Russell, P, Links, M, Grygiel, J, Hill, J, Brand, A, Byth, K, Jaworski, R, Harnett, P, Sharma, R, Wain, G, Ward, B, Papadimos, D, Crandon, A, Cummings, M, Horwood, K, Obermair, A, Perrin, L, Wyld, D, Nicklin, J, Davy, M, Oehler, MK, Hall, C, Dodd, T, Healy, T, Pittman, K, Henderson, D, Miller, J, Pierdes, J, Blomfield, P, Challis, D, Mclntosh, R, Parker, A, Brown, B, Rome, R, Allen, D, Grant, P, Hyde, S, Laurie, R, Robbie, M, Healy, D, Jobling, T, Manolitsas, T, McNealage, J, Rogers, P, Susil, B, Sumithran, E, Simpson, I, Phillips, K, Rischin, D, Fox, S, Johnson, D, Lade, S, Loughrey, M, O'Callaghan, N, Murray, W, Waring, P, Billson, V, Pyman, J, Neesham, D, Quinn, M, Underhill, C, Bell, R, Ng, LF, Blum, R, Ganju, V, Hammond, I, Leung, Y, McCartney, A, Buck, M, Haviv, I, Purdie, D, Whiteman, D, and Zeps, N

Abstract

Accurately identifying patients with high-grade serous ovarian carcinoma (HGSOC) who respond to poly(ADP-ribose) polymerase inhibitor (PARPi) therapy is of great clinical importance. Here we show that quantitative BRCA1 methylation analysis provides new insight into PARPi response in preclinical models and ovarian cancer patients. The response of 12 HGSOC patient-derived xenografts (PDX) to the PARPi rucaparib was assessed, with variable dose-dependent responses observed in chemo-naive BRCA1/2-mutated PDX, and no responses in PDX lacking DNA repair pathway defects. Among BRCA1-methylated PDX, silencing of all BRCA1 copies predicts rucaparib response, whilst heterozygous methylation is associated with resistance. Analysis of 21 BRCA1-methylated platinum-sensitive recurrent HGSOC (ARIEL2 Part 1 trial) confirmed that homozygous or hemizygous BRCA1 methylation predicts rucaparib clinical response, and that methylation loss can occur after exposure to chemotherapy. Accordingly, quantitative BRCA1 methylation analysis in a pre-treatment biopsy could allow identification of patients most likely to benefit, and facilitate tailoring of PARPi therapy.

Published
2018

11. Refined cut-off for TP53 immunohistochemistry improves prediction of TP53mutation status in ovarian mucinous tumors: implications for outcome analyses

Author

Kang, Eun Young, Cheasley, Dane, LePage, Cecile, Wakefield, Matthew J., da Cunha Torres, Michelle, Rowley, Simone, Salazar, Carolina, Xing, Zhongyue, Allan, Prue, Bowtell, David D.L., Mes-Masson, Anne-Marie, Provencher, Diane M., Rahimi, Kurosh, Kelemen, Linda E., Fasching, Peter A., Doherty, Jennifer A., Goodman, Marc T., Goode, Ellen L., Deen, Suha, Pharoah, Paul D.P., Brenton, James D., Sieh, Weiva, Mateoiu, Constantina, Sundfeldt, Karin, Cook, Linda S., Le, Nhu D., Anglesio, Michael S., Gilks, C. Blake, Huntsman, David G., Kennedy, Catherine J., Traficante, Nadia, Bowtell, D., Chenevix-Trench, G., Green, A., Webb, P., DeFazio, A., Gertig, D., Traficante, N., Fereday, S., Moore, S., Hung, J., Harrap, K., Sadkowsky, T., Pandeya, N., Malt, M., Mellon, A., Robertson, R., Bergh, T. Vanden, Jones, M., Mackenzie, P., Maidens, J., Nattress, K., Chiew, Y.E., Stenlake, A., Sullivan, H., Alexander, B., Ashover, P., Brown, S., Corrish, T., Green, L., Jackman, L., Ferguson, K., Martin, K., Martyn, A., Ranieri, B., White, J., Jayde, V., Mamers, P., Bowes, L., Galletta, L., Giles, D., Hendley, J., Alsop, K., Schmidt, T., Shirley, H., Ball, C., Young, C., Viduka, S., Tran, Hoa, Bilic, Sanela, Glavinas, Lydia, Brooks, Julia, Stuart-Harris, R., Kirsten, F., Rutovitz, J., Clingan, P., Glasgow, A., Proietto, A., Braye, S., Otton, G., Shannon, J., Bonaventura, T., Stewart, J., Begbie, S., Friedlander, M., Bell, D., Baron-Hay, S., Ferrier, A., Gard, G., Nevell, D., Pavlakis, N., Valmadre, S., Young, B., Camaris, C., Crouch, R., Edwards, L., Hacker, N., Marsden, D., Robertson, G., Beale, P., Beith, J., Carter, J., Dalrymple, C., Houghton, R., Russell, P., Links, M., Grygiel, J., Hill, J., Brand, A., Byth, K., Jaworski, R., Harnett, P., Sharma, R., Wain, G., Ward, B., Papadimos, D., Crandon, A., Cummings, M., Horwood, K., Obermair, A., Perrin, L., Wyld, D., Nicklin, J., Davy, M., Oehler, M.K., Hall, C., Dodd, T., Healy, T., Pittman, K., Henderson, D., Miller, J., Pierdes, J., Blomfield, P., Challis, D., McIntosh, R., Parker, A., Brown, B., Rome, R., Allen, D., Grant, P., Hyde, S., Laurie, R., Robbie, M., Healy, D., Jobling, T., Manolitsas, T., McNealage, J., Rogers, P., Susil, B., Sumithran, E., Simpson, I., Phillips, K., Rischin, D., Fox, S., Johnson, D., Lade, S., Loughrey, M., O'Callaghan, N., Murray, W., Waring, P., Billson, V., Pyman, J., Neesham, D., Quinn, M., Underhill, C., Bell, R., Ng, L.F., Blum, R., Ganju, V., Hammond, I., Leung, Y., McCartney, A., Buck, M., Haviv, I., Purdie, D., Whiteman, D., Zeps, N., DeFazio, Anna, Kaufmann, Scott, Churchman, Michael, Gourley, Charlie, Stephens, Andrew N., Meagher, Nicola S., Ramus, Susan J., Antill, Yoland C., Campbell, Ian, Scott, Clare L., Köbel, Martin, Gorringe, Kylie L., Cheasley, Dane, Wakefield, Matthew J., Ryland, Georgina L., Allan, Prue E., Alsop, Kathryn, Ananda, Sumitra, Anglesio, Michael S., Au-Yeung, George, Böhm, Maret, Bowtell, David D.L., Brand, Alison, Chenevix-Trench, Georgia, Christie, Michael, Chiew, Yoke-Eng, Churchman, Michael, DeFazio, Anna, Dudley, Rhiannon, Fairweather, Nicole, Fereday, Sian, Fox, Stephen B., Gilks, C. Blake, Gourley, Charlie, Hacker, Neville F., Hadley, Alison M., Hendley, Joy, Ho, Gwo-Yaw, Huntsman, David G., Hunter, Sally M., Jobling, Tom W., Kalli, Kimberly R., Kaufmann, Scott H., Kennedy, Catherine J., Köbel, Martin, Le Page, Cecile, McNally, Orla M., McAlpine, Jessica N., Mes-Masson, Anne-Marie, Mileshkin, Linda, Provencher, Diane M., Pyman, Jan, Rahimi, Kurosh, Samimi, Goli, Sharma, Ragwha, Stephens, Andrew N., Traficante, Nadia, Antill, Yoland C., Scott, Clare L., Campbell, Ian G., and Gorringe, Kylie L.

Abstract

TP53mutations are implicated in the progression of mucinous borderline tumors (MBOT) to mucinous ovarian carcinomas (MOC). Optimized immunohistochemistry (IHC) for TP53 has been established as a proxy for the TP53mutation status in other ovarian tumor types. We aimed to confirm the ability of TP53 IHC to predict TP53mutation status in ovarian mucinous tumors and to evaluate the association of TP53mutation status with survival among patients with MBOT and MOC. Tumor tissue from an initial cohort of 113 women with MBOT/MOC was stained with optimized IHC for TP53 using tissue microarrays (75.2%) or full sections (24.8%) and interpreted using established criteria as normal or abnormal (overexpression, complete absence, or cytoplasmic). Cases were considered concordant if abnormal IHC staining predicted deleterious TP53mutations. Discordant tissue microarray cases were re-evaluated on full sections and interpretational criteria were refined. The initial cohort was expanded to a total of 165 MBOT and 424 MOC for the examination of the association of survival with TP53mutation status, assessed either by TP53 IHC and/or sequencing. Initially, 82/113 (72.6%) cases were concordant using the established criteria. Refined criteria for overexpression to account for intratumoral heterogeneity and terminal differentiation improved concordance to 93.8% (106/113). In the expanded cohort, 19.4% (32/165) of MBOT showed evidence for TP53mutation and this was associated with a higher risk of recurrence, disease-specific death, and all-cause mortality (overall survival: HR = 4.6, 95% CI 1.5–14.3, p= 0.0087). Within MOC, 61.1% (259/424) harbored a TP53mutation, but this was not associated with survival (overall survival, p= 0.77). TP53 IHC is an accurate proxy for TP53mutation status with refined interpretation criteria accounting for intratumoral heterogeneity and terminal differentiation in ovarian mucinous tumors. TP53mutation status is an important biomarker to identify MBOT with a higher risk of mortality.

Published
2021
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12. Skewed X chromosome inactivation and breast and ovarian cancer status: Evidence for X-linked modifiers of BRCA1.

Author

Bonaventura T., Crouch R., Edwards L., Hacker N., Marsden D., Robertson G., Beale P., Beith J., Carter J., Dalrymple C., Hamilton A., Houghton R., Russell P., Links M., Grygiel J., Hill J., Brand A., Byth K., Jaworski R., Harnett P., Sharma R., Wain G., Purdie D., Whiteman D., Ward B., Papadimos D., Crandon A., Cummings M., Horwood K., Obermair A., Perrin L., Wyld D., Nicklin J., Davy M., Oehler M., Hall C., Dodd T., Healy T., Pittman K., Henderson D., Miller J., Pierdes J., Blomfield P., Challis D., McIntosh R., Parker A., Brown B., Rome R., Allen D., Grant P., Hyde S., Laurie R., Robbie M., Healy D., Manolitsas T., McNealage J., Rogers P., Susil B., Sumithran E., Simpson I., Haviv I., Phillips K., Rischin D., Fox S., Johnson D., Waring P., Loughrey M., O'Callaghan N., Murray B., Billson V., Pyman J., Neesham D., Quinn M., Underhill C., Ng L.F., Blum R., Ganju V., Hammond I., McCartney A., Leung Y., Buck M., Zeps N., Bell R., Jobling T., Tran H., Lose F., Duffy D.L., Kay G.F., Kedda M.A., Spurdle A.B., Bowtell D., Chenevix-Trench G., Green A., Webb P., DeFazio A., Gertig D., Traficante N., Moore S., Hung J., Fereday S., Harrap K., Sadkowsky T., Mellon A., Robertson R., Vanden Bergh T., Jones M., Maidens J., Nattress K., Chiew Y.E., Stenlake A., Sullivan H., Alexander B., Ashover P., Brown S., Corrish T., Green L., Jackman L., Martin K., Ranieri B., White J., Jayde V., Bowes L., Mamers P., Schmidt T., Shirley H., Viduka S., Bilic S., Glavinas L., Stuart-Harris R., Kirsten F., Rutovitz J., Clingan P., Glasgow A., Proietto A., Braye S., Otton G., Shannon J., Stewart J., Begbie S., Friedlander M., Bell D., Baron-Hay S., Ferrier A., Gard G., Nevell D., Pavlakis N., Young B., Camaris C., Bonaventura T., Crouch R., Edwards L., Hacker N., Marsden D., Robertson G., Beale P., Beith J., Carter J., Dalrymple C., Hamilton A., Houghton R., Russell P., Links M., Grygiel J., Hill J., Brand A., Byth K., Jaworski R., Harnett P., Sharma R., Wain G., Purdie D., Whiteman D., Ward B., Papadimos D., Crandon A., Cummings M., Horwood K., Obermair A., Perrin L., Wyld D., Nicklin J., Davy M., Oehler M., Hall C., Dodd T., Healy T., Pittman K., Henderson D., Miller J., Pierdes J., Blomfield P., Challis D., McIntosh R., Parker A., Brown B., Rome R., Allen D., Grant P., Hyde S., Laurie R., Robbie M., Healy D., Manolitsas T., McNealage J., Rogers P., Susil B., Sumithran E., Simpson I., Haviv I., Phillips K., Rischin D., Fox S., Johnson D., Waring P., Loughrey M., O'Callaghan N., Murray B., Billson V., Pyman J., Neesham D., Quinn M., Underhill C., Ng L.F., Blum R., Ganju V., Hammond I., McCartney A., Leung Y., Buck M., Zeps N., Bell R., Jobling T., Tran H., Lose F., Duffy D.L., Kay G.F., Kedda M.A., Spurdle A.B., Bowtell D., Chenevix-Trench G., Green A., Webb P., DeFazio A., Gertig D., Traficante N., Moore S., Hung J., Fereday S., Harrap K., Sadkowsky T., Mellon A., Robertson R., Vanden Bergh T., Jones M., Maidens J., Nattress K., Chiew Y.E., Stenlake A., Sullivan H., Alexander B., Ashover P., Brown S., Corrish T., Green L., Jackman L., Martin K., Ranieri B., White J., Jayde V., Bowes L., Mamers P., Schmidt T., Shirley H., Viduka S., Bilic S., Glavinas L., Stuart-Harris R., Kirsten F., Rutovitz J., Clingan P., Glasgow A., Proietto A., Braye S., Otton G., Shannon J., Stewart J., Begbie S., Friedlander M., Bell D., Baron-Hay S., Ferrier A., Gard G., Nevell D., Pavlakis N., Young B., and Camaris C.

Abstract

Background: X chromosome inactivation, which silences gene expression from one of the two X chromosomes in females, is usually random. Skewed X inactivation has been implicated in both the expression and the suppression of X-linked disease phenotypes and has been reported to occur more frequently in breast and ovarian cancer patients, including BRCA1 or BRCA2 mutation carriers, than in control subjects. Method(s): We assessed the pattern of X chromosome inactivation using methylation-specific polymerase chain reaction amplification of the exon 1 microsatellite region of the X-linked androgen receptor (AR) gene in DNA from blood samples obtained from control subjects without a personal history of breast or ovarian cancer (n = 735), ovarian cancer patients (n = 313), familial breast cancer patients who did not carry mutations in BRCA1 or BRCA2 (n = 235), and affected and unaffected carriers of mutations in BRCA1 (n = 260) or BRCA2 (n = 63). We defined the pattern of X chromosome inactivation as skewed when the same X chromosome was active in at least 90% of cells. The association between skewed X inactivation and disease and/or BRCA mutation status was assessed by logistic regression analysis. The association between skewed X inactivation and age at cancer diagnosis was assessed by Cox proportional hazards regression analysis. All statistical tests were two-sided. Result(s): The age-adjusted frequency of skewed X inactivation was not statistically significantly higher in ovarian cancer or familial breast cancer case subjects compared with control subjects. Skewed X inactivation was higher in BRCA1 mutation carriers than in control subjects (odds ratio [OR] = 2.7, 95% confidence interval [CI] = 1.1 to 6.2; P =. 02), particularly among unaffected women (OR = 6.1, 95% CI = 1.5 to 31.8; P =. 005). Among BRCA1 mutation carriers, those with skewed X inactivation were older at diagnosis of breast or ovarian cancer than those without skewed X inactivation (hazard ratio [HR] o

Published
2012

13. Validating genetic risk associations for ovarian cancer through the international Ovarian Cancer Association Consortium.

Author

Chenevix-Trench G., Gard G., Nevell D., Young B., Nattress K., Beale P., Beith J., Carter J., Dalrymple C., Hamilton A., Houghton R., Russell P., Crandon A., Cummings M., Horwood K., Obermair A., Wyld D., Nicklin J., Perrin L., Ward B., Papadimos D., Davy M., Hall C., Dodd T., Healy T., Pittman K., Henderson D., Miller J., Pierdes J., Jayde V., Blomfield P., Challis D., McIntosh R., Parker A., Brown B., Rome R., Allen D., Grant P., Hyde S., Laurie R., Robbie M., Traficante N., Fereday S., Bowes L., Phillips K., Rischin D., Waring P., Loughrey M., O'Callaghan N., Murray B., Haviv I., Billson V., Galloway S., Pyman J., Quinn M., Hammond I., McCartney A., Leung Y., Jobling T., Tran H., Pearce C.L., Near A.M., Van Den Berg D.J., Ramus S.J., Gentry-Maharaj A., Menon U., Gayther S.A., Anderson A.R., Edlund C.K., Wu A.H., Chen X., Beesley J., Webb P., Holt S.K., Chen C., Doherty J.A., Rossing M.A., Whittemore A.S., McGuire V., DiCioccio R.A., Goodman M.T., Lurie G., Carney M.E., Wilkens L.R., Ness R.B., Moysich K.B., Edwards R., Jennison E., Kjaer S.K., Hogdall E., Hogdall C.K., Goode E.L., Sellers T.A., Vierkant R.A., Cunningham J.C., Schildkraut J.M., Berchuck A., Moorman P.G., Iversen E.S., Cramer D.W., Terry K.L., Vitonis A.F., Titus-Ernstoff L., Song H., Pharoah P.D.P., Spurdle A.B., Anton-Culver H., Ziogas A., Brewster W., Galitovskiy V., Gertig D., Vanden Bergh T., Camaris C., Crouch R., Edwards L., Hacker N., Marsden D., Robertson G., DeFazio A., Hung J., Chiew Y.E., Stenlake A., Sullivan H., Brand A., Jaworski R., Harnett P., Wain G., Green A., Moore S., Harrap K., Sadkowsky T., Purdie D., Whiteman D., Alexander B., Ashover P., Brown S., Corrish T., Green L., Jackman L., Martin K., Ranieri B., White J., Mamers P., Healy D., Maniolitas T., McNealage J., Rogers P., Susil B., Veitch A., Constable J., Ping Tong S., Robinson I., Simpson I., Schmidt T., Shirley H., Viduka S., Bilic S., Glavinas L., Zeps N., Mellon A., Robertson R., Proietto A., Braye S., Otton G., Bonaventura T., Stewart J., Friedlander M., Maidens J., Bell D., Baron-Hay S., Ferrier A., Chenevix-Trench G., Gard G., Nevell D., Young B., Nattress K., Beale P., Beith J., Carter J., Dalrymple C., Hamilton A., Houghton R., Russell P., Crandon A., Cummings M., Horwood K., Obermair A., Wyld D., Nicklin J., Perrin L., Ward B., Papadimos D., Davy M., Hall C., Dodd T., Healy T., Pittman K., Henderson D., Miller J., Pierdes J., Jayde V., Blomfield P., Challis D., McIntosh R., Parker A., Brown B., Rome R., Allen D., Grant P., Hyde S., Laurie R., Robbie M., Traficante N., Fereday S., Bowes L., Phillips K., Rischin D., Waring P., Loughrey M., O'Callaghan N., Murray B., Haviv I., Billson V., Galloway S., Pyman J., Quinn M., Hammond I., McCartney A., Leung Y., Jobling T., Tran H., Pearce C.L., Near A.M., Van Den Berg D.J., Ramus S.J., Gentry-Maharaj A., Menon U., Gayther S.A., Anderson A.R., Edlund C.K., Wu A.H., Chen X., Beesley J., Webb P., Holt S.K., Chen C., Doherty J.A., Rossing M.A., Whittemore A.S., McGuire V., DiCioccio R.A., Goodman M.T., Lurie G., Carney M.E., Wilkens L.R., Ness R.B., Moysich K.B., Edwards R., Jennison E., Kjaer S.K., Hogdall E., Hogdall C.K., Goode E.L., Sellers T.A., Vierkant R.A., Cunningham J.C., Schildkraut J.M., Berchuck A., Moorman P.G., Iversen E.S., Cramer D.W., Terry K.L., Vitonis A.F., Titus-Ernstoff L., Song H., Pharoah P.D.P., Spurdle A.B., Anton-Culver H., Ziogas A., Brewster W., Galitovskiy V., Gertig D., Vanden Bergh T., Camaris C., Crouch R., Edwards L., Hacker N., Marsden D., Robertson G., DeFazio A., Hung J., Chiew Y.E., Stenlake A., Sullivan H., Brand A., Jaworski R., Harnett P., Wain G., Green A., Moore S., Harrap K., Sadkowsky T., Purdie D., Whiteman D., Alexander B., Ashover P., Brown S., Corrish T., Green L., Jackman L., Martin K., Ranieri B., White J., Mamers P., Healy D., Maniolitas T., McNealage J., Rogers P., Susil B., Veitch A., Constable J., Ping Tong S., Robinson I., Simpson I., Schmidt T., Shirley H., Viduka S., Bilic S., Glavinas L., Zeps N., Mellon A., Robertson R., Proietto A., Braye S., Otton G., Bonaventura T., Stewart J., Friedlander M., Maidens J., Bell D., Baron-Hay S., and Ferrier A.

Abstract

The search for genetic variants associated with ovarian cancer risk has focused on pathways including sex steroid hormones, DNA repair, and cell cycle control. The Ovarian Cancer Association Consortium (OCAC) identified 10 single-nucleotide polymorphisms (SNPs) in genes in these pathways, which had been genotyped by Consortium members and a pooled analysis of these data was conducted. Three of the 10 SNPs showed evidence of an association with ovarian cancer at P<=0.10 in a log-additive model: rs2740574 in CYP3A4 (P=0.011), rs1805386 in LIG4 (P=0.007), and rs3218536 in XRCC2 (P=0.095). Additional genotyping in other OCAC studies was undertaken and only the variant in CYP3A4, rs2740574, continued to show an association in the replication data among homozygous carriers: ORhomozygous(hom)=2.50 (95% CI 0.54-11.57, P=0.24) with 1406 cases and 2827 controls. Overall, in the combined data the odds ratio was 2.81 among carriers of two copies of the minor allele (95% CI 1.20-6.56, P=0.017, phet across studies=0.42) with 1969 cases and 3491 controls. There was no association among heterozygous carriers. CYP3A4 encodes a key enzyme in oestrogen metabolism and our finding between rs2740574 and risk of ovarian cancer suggests that this pathway may be involved in ovarian carcinogenesis. Additional follow-up is warranted. © 2009 Cancer Research UK.

Published
2009

14. Body size and risk of epithelial ovarian and related cancers: A population-based case-control study.

Author

Stewart J., Shirley H., Viduka S., Bilic S., Glavinas L., Proietto A., Braye S., Otton G., Bonaventura T., Friedlander M., Bell D., Baron-Hay S., Ferrier A., Gard G., Nevell D., Young B., Camaris C., Crouch R., Edwards L., Hacker N., Marsden D., Robertson G., Beale P., Beith J., Carter J., Dalrymple C., Hamilton A., Houghton R., Russell P., Brand A., Jaworski R., Harnett P., Wain G., Crandon A., Cummings M., Horwood K., Obermair A., Wyld D., Nicklin J., Perrin L., Ward B., Davy M., Hall C., Dodd T., Healy T., Pittman K., Henderson D., Hyde S., Miller J., Pierdes J., Blomfield P., Challis D., McIntosh R., Parker A., Brown B., Rome R., Allen D., Grant P., Laurie R., Robbie M., Healy D., Maniolitas T., McNealage J., Rogers P., Susil B., Veitch A., Constable J., Ping Tong S., Robinson I., Simpson I., Phillips K., Rischin D., Waring P., Loughrey M., O'Callaghan N., Murray B., Billson V., Galloway S., Pyman J., Quinn M., Hammond I., McCartney A., Leung Y., Haviv I., Zeps N., Parsons P.G., Hayward N., Jobling T., Tran H., Olsen C.M., Nagle C.M., Whiteman D., Purdie D., Green A.C., Webb P., Bowtell D., Chenevix-Trench G., Green A., DeFazio A., Gertig D., Traficante N., Moore S., Hung J., Fereday S., Harrap K., Sadkowsky T., Mellon A., Robertson R., Vanden Bergh T., Maidens J., Nattress K., Chiew Y.E., Stenlake A., Sullivan H., Alexander B., Ashover P., Brown S., CorrGreenish T., Green L., Jackman L., Martin K., Ranieri B., White J., Jayde V., Bowes L., Mamers P., Schmidt T., Stewart J., Shirley H., Viduka S., Bilic S., Glavinas L., Proietto A., Braye S., Otton G., Bonaventura T., Friedlander M., Bell D., Baron-Hay S., Ferrier A., Gard G., Nevell D., Young B., Camaris C., Crouch R., Edwards L., Hacker N., Marsden D., Robertson G., Beale P., Beith J., Carter J., Dalrymple C., Hamilton A., Houghton R., Russell P., Brand A., Jaworski R., Harnett P., Wain G., Crandon A., Cummings M., Horwood K., Obermair A., Wyld D., Nicklin J., Perrin L., Ward B., Davy M., Hall C., Dodd T., Healy T., Pittman K., Henderson D., Hyde S., Miller J., Pierdes J., Blomfield P., Challis D., McIntosh R., Parker A., Brown B., Rome R., Allen D., Grant P., Laurie R., Robbie M., Healy D., Maniolitas T., McNealage J., Rogers P., Susil B., Veitch A., Constable J., Ping Tong S., Robinson I., Simpson I., Phillips K., Rischin D., Waring P., Loughrey M., O'Callaghan N., Murray B., Billson V., Galloway S., Pyman J., Quinn M., Hammond I., McCartney A., Leung Y., Haviv I., Zeps N., Parsons P.G., Hayward N., Jobling T., Tran H., Olsen C.M., Nagle C.M., Whiteman D., Purdie D., Green A.C., Webb P., Bowtell D., Chenevix-Trench G., Green A., DeFazio A., Gertig D., Traficante N., Moore S., Hung J., Fereday S., Harrap K., Sadkowsky T., Mellon A., Robertson R., Vanden Bergh T., Maidens J., Nattress K., Chiew Y.E., Stenlake A., Sullivan H., Alexander B., Ashover P., Brown S., CorrGreenish T., Green L., Jackman L., Martin K., Ranieri B., White J., Jayde V., Bowes L., Mamers P., and Schmidt T.

Abstract

Different subtypes of ovarian cancer appear to have different causes; however, the association between body mass index (BMI) and the different subtypes is unclear. We examined the associations between body-mass index (BMI) and weight gain and risk of the different histological subtypes of epithelial ovarian cancer in a case-control study in Australia. Cases aged 18-79 with a new diagnosis of invasive epithelial ovarian cancer (n = 1,269) or borderline tumor (n = 311) were identified through a network of clinics and cancer registries throughout Australia. Controls (n = 1,509) were selected from the Electoral Roll. Height and weight (1 year previously, at age 20 and maximum weight) and other risk factor information were ascertained via a self-administered questionnaire. Obesity was positively associated with clear cell tumors (Odds Ratio 2.3; 95% confidence interval 1.2-4.2) but not invasive endometrioid or mucinous tumors. Although there was no association with invasive serous tumors overall (0.9; 0.7-1.2), we did see an increased risk of serous peritoneal tumors (2.9; 1.7-4.9), but not of serous tumors of the ovary and fallopian tube. Of the borderline subtypes, obesity was positively associated with serous (1.8; 1.1-2.8) but not mucinous tumors (1.1; 0.7-1.7). Overweight was not associated with any subtype overall. There was no association with BMI at age 20, or weight gain for any of the histological subtypes. These results add to the current evidence that obesity increases a woman's risk of developing distinct histological subtypes of ovarian cancer. © 2008 Wiley-Liss, Inc.

Published
2008

15. Recreational physical activity and epithelial ovarian cancer: A case-control study, systematic review, and meta-analysis.

Author

Otton G., Bilic S., Glavinas L., Proietto A., Braye S., Hung J., Bonaventura T., Stewart J., Friedlander M., Bell D., Baron-Hay S., Ferrier A., Gard G., Nevell D., Young B., Camaris C., Crouch R., Edwards L., Hacker N., Marsden D., Robertson G., Beale P., Beith J., Carter J., Dalrymple C., Hamilton A., Houghton R., Russell P., Brand A., Jaworski R., Harnett P., Wain G., Crandon A., Cummings M., Horwood K., Obermair A., Wyld D., Nicklin J., Perrin L., Ward B., Davy M., Hall C., Dodd T., Healy T., Pittman K., Henderson D., Hyde S., Miller J., Pierdes J., Blomfield P., Challis D., McIntosh R., Parker A., Rome R., Allen D., Grant P., Laurie R., Robbie M., Healy D., Jobling T., Maniolitas T., McNealage J., Rogers P., Susil B., Veitch A., Constable J., Ping Tong S., Robinson I., Simpson I., Phillips K., Rischin D., Waring P., Loughrey M., O'Callaghan N., Murray B., Billson V., Galloway S., Pyman J., Quinn M., Hammond I., McCartney A., Leung Y., Haviv I., Purdie D., Zeps N., Parsons P.G., Hayward N., Olsen C.M., Bain C.J., Jordan S.J., Nagle C.M., Green A.C., Whiteman D., Webb P., Bowtell D., Chenevix-Trench G., Green A., Defazio A., Gertig D., Traficante N., Moore S., Fereday S., Harrap K., Sadkowsky T., Mellon A., Robertson R., Vanden Bergh T., Maidens J., Nattress K., Chiew Y.E., Stenlake A., Sullivan H., Alexander B., Ashover P., Brown B., Corrish T., Green L., Jackman L., Martin K., Ranieri B., White J., Jayde V., Bowes L., Mamers P., Schmidt T., Shirley H., Viduka S., Tran H., Otton G., Bilic S., Glavinas L., Proietto A., Braye S., Hung J., Bonaventura T., Stewart J., Friedlander M., Bell D., Baron-Hay S., Ferrier A., Gard G., Nevell D., Young B., Camaris C., Crouch R., Edwards L., Hacker N., Marsden D., Robertson G., Beale P., Beith J., Carter J., Dalrymple C., Hamilton A., Houghton R., Russell P., Brand A., Jaworski R., Harnett P., Wain G., Crandon A., Cummings M., Horwood K., Obermair A., Wyld D., Nicklin J., Perrin L., Ward B., Davy M., Hall C., Dodd T., Healy T., Pittman K., Henderson D., Hyde S., Miller J., Pierdes J., Blomfield P., Challis D., McIntosh R., Parker A., Rome R., Allen D., Grant P., Laurie R., Robbie M., Healy D., Jobling T., Maniolitas T., McNealage J., Rogers P., Susil B., Veitch A., Constable J., Ping Tong S., Robinson I., Simpson I., Phillips K., Rischin D., Waring P., Loughrey M., O'Callaghan N., Murray B., Billson V., Galloway S., Pyman J., Quinn M., Hammond I., McCartney A., Leung Y., Haviv I., Purdie D., Zeps N., Parsons P.G., Hayward N., Olsen C.M., Bain C.J., Jordan S.J., Nagle C.M., Green A.C., Whiteman D., Webb P., Bowtell D., Chenevix-Trench G., Green A., Defazio A., Gertig D., Traficante N., Moore S., Fereday S., Harrap K., Sadkowsky T., Mellon A., Robertson R., Vanden Bergh T., Maidens J., Nattress K., Chiew Y.E., Stenlake A., Sullivan H., Alexander B., Ashover P., Brown B., Corrish T., Green L., Jackman L., Martin K., Ranieri B., White J., Jayde V., Bowes L., Mamers P., Schmidt T., Shirley H., Viduka S., and Tran H.

Abstract

It remains unclear whether physical activity is associated with epithelial ovarian cancer risk. We therefore examined the association between recreational physical activity and risk of ovarian cancer in a national population-based case-control study in Australia. We also systematically reviewed all the available evidence linking physical activity with ovarian cancer to provide the best summary estimate of the association. The case-control study included women ages 18 to 79 years with a new diagnosis of invasive (n = 1,269) or borderline (n = 311) epithelial ovarian cancer identified through a network of clinics, physicians, and state cancer registries throughout Australia. Controls (n = 1,509) were randomly selected from the national electoral roll and were frequency matched to cases by age and state. For the systematic review, we identified eligible studies using Medline, the ISI Science Citation Index, and manual review of retrieved references, and included all case-control or cohort studies that permitted assessment of an association between physical activity (recreational/ occupational/sedentary behavior) and histologically confirmed ovarian cancer. Meta-analysis was restricted to the subset of these studies that reported on recreational physical activity. In our case-control study, we observed weakly inverse or null associations between recreational physical activity and risk of epithelial ovarian cancer overall. There was no evidence that the effects varied by tumor behavior or histologic subtype. Twelve studies were included in the meta-analysis, which gave summary estimates of 0.79 (95% confidence interval, 0.70-0.85) for case-control studies and 0.81 (95% confidence interval, 0.57-1.17) for cohort studies for the risk of ovarian cancer associated with highest versus lowest levels of recreational physical activity. Thus, pooled results fromobservational studies suggest that a modest inverse association exists between level of recreational physical activity a

Published
2008

16. Consortium analysis of 7 candidate SNPs for ovarian cancer.

Author

Harrap K., Nevell D., Young B., Camaris C., Crouch R., Edwards L., Hacker N., Marsden D., Robertson G., Beale P., Beith J., Carter J., Dalrymple C., Hamilton A., Houghton R., Russell P., Brand A., Jaworski R., Harnett P., Wain G., Crandon A., Cummings M., Horwood K., Obermair A., Wyld D., Nicklin J., Papadimos D., Perrin L., Ward B., Davy M., Hall C., Dodd T., Healy T., Pittman K., Henderson D., Hyde S., Miller J., Pierdes J., Blomfield P., Challis D., McIntosh R., Parker A., Brown B., Rome R., Allen D., Grant P., Laurie R., Robbie M., Healy D., Maniolitas T., McNealage J., Rogers P., Susil B., Veitch A., Constable J., Ping Tong S., Robinson I., Simpson I., Phillips K., Rischin D., Waring P., Loughrey M., O'Callaghan N., Murray B., Billson V., Galloway S., Pyman J., Quinn M., Hammond I., McCartney A., Leung Y., Haviv I., Purdie D., Whiteman D., Zeps N., Jobling T., Tran H., Ramus S.J., Vierkant R.A., Johnatty S.E., Pike M.C., Van Den Berg D.J., Wu A.H., Pearce C.L., Menon U., Gentry-Maharaj A., Gayther S.A., DiCioccio R.A., McGuire V., Whittemore A.S., Song H., Easton D.F., Pharoah P.D.P., Garcia-Closas M., Chanock S., Lissowska J., Brinton L., Terry K.L., Cramer D.W., Tworoger S.S., Hankinson S.E., Berchuck A., Moorman P.G., Schildkraut J.M., Cunningham J.M., Liebow M., Kjaer S.K., Hogdall E., Hogdall C., Blaakaer J., Ness R.B., Moysich K.B., Edwards R.P., Carney M.E., Lurie G., Goodman M.T., Wang-Gohrke S., Kropp S., Chang-Claude J., Webb P., Chen X., Beesley J., Chenevix-Trench G., Goode E.L., Bowtell D., Green A., DeFazio A., Gertig D., Traficante N., Moore S., Hung J., Fereday S., Sadkowsky T., Mellon A., Robertson R., Vanden Bergh T., Maidens J., Nattress K., Chiew Y.E., Stenlake A., Sullivan H., Alexander B., Ashover P., Brown S., Corrish T., Green L., Jackman L., Martin K., Ranieri B., White J., Jayde V., Bowes V.L., Mamers P., Schmidt T., Shirley H., Viduka S., Bilic S., Glavinas L., Proietto A., Braye S., Otton G., Bonaventura T., Stewart J., Friedlander M., Bell D., Baron-Hay S., Ferrier A., Gard G., Harrap K., Nevell D., Young B., Camaris C., Crouch R., Edwards L., Hacker N., Marsden D., Robertson G., Beale P., Beith J., Carter J., Dalrymple C., Hamilton A., Houghton R., Russell P., Brand A., Jaworski R., Harnett P., Wain G., Crandon A., Cummings M., Horwood K., Obermair A., Wyld D., Nicklin J., Papadimos D., Perrin L., Ward B., Davy M., Hall C., Dodd T., Healy T., Pittman K., Henderson D., Hyde S., Miller J., Pierdes J., Blomfield P., Challis D., McIntosh R., Parker A., Brown B., Rome R., Allen D., Grant P., Laurie R., Robbie M., Healy D., Maniolitas T., McNealage J., Rogers P., Susil B., Veitch A., Constable J., Ping Tong S., Robinson I., Simpson I., Phillips K., Rischin D., Waring P., Loughrey M., O'Callaghan N., Murray B., Billson V., Galloway S., Pyman J., Quinn M., Hammond I., McCartney A., Leung Y., Haviv I., Purdie D., Whiteman D., Zeps N., Jobling T., Tran H., Ramus S.J., Vierkant R.A., Johnatty S.E., Pike M.C., Van Den Berg D.J., Wu A.H., Pearce C.L., Menon U., Gentry-Maharaj A., Gayther S.A., DiCioccio R.A., McGuire V., Whittemore A.S., Song H., Easton D.F., Pharoah P.D.P., Garcia-Closas M., Chanock S., Lissowska J., Brinton L., Terry K.L., Cramer D.W., Tworoger S.S., Hankinson S.E., Berchuck A., Moorman P.G., Schildkraut J.M., Cunningham J.M., Liebow M., Kjaer S.K., Hogdall E., Hogdall C., Blaakaer J., Ness R.B., Moysich K.B., Edwards R.P., Carney M.E., Lurie G., Goodman M.T., Wang-Gohrke S., Kropp S., Chang-Claude J., Webb P., Chen X., Beesley J., Chenevix-Trench G., Goode E.L., Bowtell D., Green A., DeFazio A., Gertig D., Traficante N., Moore S., Hung J., Fereday S., Sadkowsky T., Mellon A., Robertson R., Vanden Bergh T., Maidens J., Nattress K., Chiew Y.E., Stenlake A., Sullivan H., Alexander B., Ashover P., Brown S., Corrish T., Green L., Jackman L., Martin K., Ranieri B., White J., Jayde V., Bowes V.L., Mamers P., Schmidt T., Shirley H., Viduka S., Bilic S., Glavinas L., Proietto A., Braye S., Otton G., Bonaventura T., Stewart J., Friedlander M., Bell D., Baron-Hay S., Ferrier A., and Gard G.

Abstract

The Ovarian Cancer Association Consortium selected 7 candidate single nucleotide polymorphisms (SNPs), for which there is evidence from previous studies of an association with variation in ovarian cancer or breast cancer risks. The SNPs selected for analysis were F31I (rs2273535) in AURKA, N372H (rs144848) in BRCA2, rs2854344 in intron 17 of RB1, rs2811712 5' flanking CDKN2A, rs523349 in the 3' UTR of SRD5A2, D302H (rs1045485) in CASP8 and L10P (rs1982073) in TGFB1. Fourteen studies genotyped 4,624 invasive epithelial ovarian cancer cases and 8,113 controls of white non-Hispanic origin. A marginally significant association was found for RB1 when all studies were included [ordinal odds ratio (OR) 0.88 (95% confidence interval (CI) 0.79-1.00) p = 0.041 and dominant OR 0.87 (95% CI 0.76-0.98) p = 0.025]; when the studies that originally suggested an association were excluded, the result was suggestive although no longer statistically significant (ordinal OR 0.92, 95% CI 0.79-1.06). This SNP has also been shown to have an association with decreased risk in breast cancer. There was a suggestion of an association for AURKA, when one study that caused significant study heterogeneity was excluded [ordinal OR 1.10 (95% CI 1.01-1.20) p = 0.027; dominant OR 1.12 (95% CI 1.01-1.24) p = 0.03]. The other 5 SNPs in BRCA2, CDKN2A, SRD5A2, CASP8 and TGFB1 showed no association with ovarian cancer risk; given the large sample size, these results can also be considered to be informative. These null results for SNPs identified from relatively large initial studies shows the importance of replicating associations by a consortium approach. © 2008 Wiley-Liss, Inc.

Published
2008

17. Talcum powder, chronic pelvic inflammation and NSAIDs in relation to risk of epithelial ovarian cancer.

Author

Proietto A., Vanden Bergh T., Maidens J., Brand A., Jaworski R., Harnett P., Wain G., Crandon A., Cummings M., Horwood K., Obermair A., Wyld D., Nicklin J., Perrin L., Ward B., Davy M., Hall C., Dodd T., Healy T., Pittman K., Henderson D., Hyde S., Miller J., Pierdes J., Blomfield P., Challis D., McIntosh R., Parker A., Brown B., Rome R., Allen D., Grant P., Laurie R., Robbie M., Healy D., Maniolitas T., McNealage J., Rogers P., Susil B., Veitch A., Constable J., Ping Tong S., Robinson I., Simpson I., Phillips K., Rischin D., Waring P., Loughrey M., O'Callaghan N., Murray B., Billson V., Galloway S., Pyman J., Quinn M., Hammond I., McCartney A., Leung Y., Haviv I., Zeps N., Parsons P.G., Hayward N., Purdie D., Whiteman D., Jobling T., Tran H., Merritt M.A., Green A.C., Nagle C.M., Webb P.M., Bowtell D., Chenevix-Trench G., Green A., DeFazio A., Gertig D., Traficante N., Moore S., Hung J., Fereday S., Harrap K., Sadkowsky T., Mellon A., Robertson R., Nattress K., Chiew Y.E., Stenlake A., Sullivan H., Alexander B., Ashover P., Brown S., Corrish T., Green L., Jackman L., Martin K., Ranieri B., White J., Jayde V., Bowes L., Mamers P., Schmidt T., Shirley H., Viduka S., Bilic S., Glavinas L., Braye S., Otton G., Bonaventura T., Stewart J., Friedlander M., Bell D., Baron-Hay S., Ferrier A., Gard G., Nevell D., Young B., Camaris C., Crouch R., Edwards L., Hacker N., Marsden D., Robertson G., Beale P., Beith J., Carter J., Dalrymple C., Hamilton A., Houghton R., Russell P., Proietto A., Vanden Bergh T., Maidens J., Brand A., Jaworski R., Harnett P., Wain G., Crandon A., Cummings M., Horwood K., Obermair A., Wyld D., Nicklin J., Perrin L., Ward B., Davy M., Hall C., Dodd T., Healy T., Pittman K., Henderson D., Hyde S., Miller J., Pierdes J., Blomfield P., Challis D., McIntosh R., Parker A., Brown B., Rome R., Allen D., Grant P., Laurie R., Robbie M., Healy D., Maniolitas T., McNealage J., Rogers P., Susil B., Veitch A., Constable J., Ping Tong S., Robinson I., Simpson I., Phillips K., Rischin D., Waring P., Loughrey M., O'Callaghan N., Murray B., Billson V., Galloway S., Pyman J., Quinn M., Hammond I., McCartney A., Leung Y., Haviv I., Zeps N., Parsons P.G., Hayward N., Purdie D., Whiteman D., Jobling T., Tran H., Merritt M.A., Green A.C., Nagle C.M., Webb P.M., Bowtell D., Chenevix-Trench G., Green A., DeFazio A., Gertig D., Traficante N., Moore S., Hung J., Fereday S., Harrap K., Sadkowsky T., Mellon A., Robertson R., Nattress K., Chiew Y.E., Stenlake A., Sullivan H., Alexander B., Ashover P., Brown S., Corrish T., Green L., Jackman L., Martin K., Ranieri B., White J., Jayde V., Bowes L., Mamers P., Schmidt T., Shirley H., Viduka S., Bilic S., Glavinas L., Braye S., Otton G., Bonaventura T., Stewart J., Friedlander M., Bell D., Baron-Hay S., Ferrier A., Gard G., Nevell D., Young B., Camaris C., Crouch R., Edwards L., Hacker N., Marsden D., Robertson G., Beale P., Beith J., Carter J., Dalrymple C., Hamilton A., Houghton R., and Russell P.

Abstract

Chronic inflammation has been proposed as the possible causal mechanism that explains the observed association between certain risk factors, such as the use of talcum powder (talc) in the pelvic region and epithelial ovarian cancer. To address this issue we evaluated the potential role of chronic local ovarian inflammation in the development of the major subtypes of epithelial ovarian cancer. Factors potentially linked to ovarian inflammation were examined in an Australia-wide case-control study comprising 1,576 women with invasive and low malignant potential (LMP) ovarian tumours and 1,509 population-based controls. We confirmed a statistically significant increase in ovarian cancer risk associated with use of talc in the pelvic region (adjusted odds ratio 1.17, 95% CI: 1.01-1.36) that was strongest for the serous and endometrioid subtypes although the latter was not statistically significant (adjusted odds ratios 1.21, 95% CI 1.03-1.44 and 1.18, 95% CI 0.81-1.70, respectively). Other factors potentially associated with ovarian inflammation (pelvic inflammatory disease, human papilloma virus infection and mumps) were not associated with risk but, like others, we found an increased risk of endometrioid and clear cell ovarian cancer only among women with a history of endometriosis. Regular use of aspirin and other nonsteroidal anti-inflammatory drugs was inversely associated with risk of LMP mucinous ovarian tumours only. We conclude that on balance chronic inflammation does not play a major role in the development of ovarian cancer. © 2007 Wiley-Liss, Inc.

Published
2007

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