Citations 13
Genome-wide Analysis Identifies Novel Loci Associated with Ovarian Cancer Outcomes: Findings from the Ovarian Cancer Association Consortium
Johnatty, Sharon E. , Kar, Siddhartha , Beesley, Jonathan, Lu, Yi , Gao, Bo , Fasching, Peter A. , Hein, Alexander , Ekici, Arif B. , Beckmann, Matthias W. , Lambrechts, Diether , Nieuwenhuysen, Els Van , Vergote, Ignace , Lambrechts, Sandrina, Rossing, Mary Anne, Chang‐Claude, Jenny , Ness, Roberta B., Moysich, Kirsten B., Levine, Douglas A. , Kiemeney, Lambertus A. , Massuger, Leon F.A.G. , Lubiński, Jan , Jakubowska, Anna , Brinton, Louise A. , Lissowska, Jolanta , Wentzensen, Nicolas , Song, Honglin , Rhenius, Valerie , Campbell, Ian , Eccles, Diana , Sieh, Weiva , Whittemore, Alice S. , McGuire, Valerie , Rothstein, Joseph H. , Sutphen, Rebecca , Gayther, Simon A. , Menon, Usha , Ramus, Susan J. , Pearce, Celeste Leigh, Pike, Malcolm C. , Wu, Anna H. , Kupryjańczyk, Jolanta , Dansonka‐Mieszkowska, Agnieszka , Rzepecka, Iwona K. , Śpiewankiewicz, Beata, Goodman, Marc T. , Carney, Michael E., Thompson, Pamela J., Heitz, Florian , Schwaab, Ira, Harter, Philipp , Pisterer, Jacobus, Hillemanns, Peter , Group, on behalf of the AGO Study, Walsh, Christine M. , Lester, Jenny, Oršulić, Sandra , Winham, Stacey J. , Earp, Madalene A. , Fogarty, Zachary C. , Høgdall, Estrid , Jensen, Allan , Cunningham, Julie M. , Vierkant, Robert A. , Schildkraut, Joellen M. , Iversen, Edwin S., Terry, Kathryn L. , Orlow, Irene , Bean, Yukie T., Høgdall, Claus , Lundvall, Lene, McNeish, Iain A. , Paul, James, Carty, Karen , Glasspool, Rosalind , Sellers, Thomas , Kennedy, Catherine J. , Chiew, Yoke-Eng , MacGregor, Stuart , Goode, Ellen L. , DeFazio, Anna , Webb, Penelope M. , Chenevix‐Trench, Georgia , Lambrechts, Diether , Earp, Madalene, Fazio, Anna de , Tyrer, Jonathan P. , Beesley, Jonathan, Doherty, Jennifer A. , Modugno, Francesmary , Gronwald, Jacek , Cybulski, Cezary , Anton‐Culver, Hoda , Ziogas, Argyrios , Gentry‐Maharaj, Aleksandra , Stram, Daniel O. , Wilkens, Lynne R. , Bois, Andreas du , Group, on behalf of the AGO Study, Karlan, Beth Y. , Lester, Jenny, Larson, Melissa C. , Kjær, Susanne K. , Fridley, Brooke L. , Cramer, Daniel W. , Bandera, Elisa V. , Pejovic, Tanja B. , Siddiqui, Nadeem , Berchuck, Andrew , Pharoah, Paul D.P. , Winham, Stacey J , Lambrechts, Diether , Kiemeney, Lambertus A , McNeish, Iain A , Ramus, Susan J , Webb, Penelope M , Hein, Alexander , Hillemanns, Peter , Jensen, Allan , Vierkant, Robert A , Eccles, Diana , Menon, Usha , Moysich, Kirsten , Orlow, Irene , Lissowska, Jolanta , Campbell, Ian G , Glasspool, Rosalind , Kennedy, Catherine J , Fogarty, Zachary C , Heitz, Florian , Jakubowska, Anna , Kupryjanczyk, Jolanta , Lambrechts, Diether , Sieh, Weiva , Ekici, Arif B , Lu, Yi , MacGregor, Stuart , Chenevix-Trench, Georgia , Høgdall, Estrid , Høgdall, Claus K , Kar, Siddhartha , Lubinski, Jan , Goodman, Marc T
Clinical Cancer Research | July 7, 2015 | Volume: 21 | Issue: 23 | Pages: 5264-5276
Abstract Purpose: Chemotherapy resistance remains a major challenge in the treatment of ovarian cancer. We hypothesize that germline polymorphisms might be associated with clinical outcome. Experimental Design: We analyzed approximately 2.8 million genotyped and imputed SNPs from the iCOGS experiment for progression-free survival (PFS) and overall survival (OS) in 2,901 European epithelial ovarian cancer (EOC) patients who underwent first-line treatment of cytoreductive surgery and chemotherapy regardless of regimen, and in a subset of 1,098 patients treated with ≥4 cycles of paclitaxel and carboplatin at standard doses. We evaluated the top SNPs in 4,434 EOC patients, including patients from The Cancer Genome Atlas. In addition, we conducted pathway analysis of all intragenic SNPs and tested their association with PFS and OS using gene set enrichment analysis. Results: Five SNPs were significantly associated (P ≤ 1.0 × 10−5) with poorer outcomes in at least one of the four analyses, three of which, rs4910232 (11p15.3), rs2549714 (16q23), and rs6674079 (1q22), were located in long noncoding RNAs (lncRNAs) RP11-179A10.1, RP11-314O13.1, and RP11-284F21.8, respectively (P ≤ 7.1 × 10−6). ENCODE ChIP-seq data at 1q22 for normal ovary show evidence of histone modification around RP11-284F21.8, and rs6674079 is perfectly correlated with another SNP within the super-enhancer MEF2D, expression levels of which were reportedly associated with prognosis in another solid tumor. YAP1- and WWTR1 (TAZ)-stimulated gene expression and high-density lipoprotein (HDL)-mediated lipid transport pathways were associated with PFS and OS, respectively, in the cohort who had standard chemotherapy (pGSEA ≤6 × 10−3). Conclusions: We have identified SNPs in three lncRNAs that might be important targets for novel EOC therapies. Clin Cancer Res; 21(23); 5264–76. ©2015 AACR.
Cell-type-specific enrichment of risk-associated regulatory elements at ovarian cancer susceptibility loci
Coetzee, Simon G. , Shen, Howard C., Hazelett, Dennis J. , Lawrenson, Kate , Kuchenbaecker, Karoline , Rhie, Suhn K. , Levanon, Keren , Karst, Alison M., Drapkin, Ronny , Ramus, Susan J. , Offit, Kenneth, Chenevix‐Trench, Georgia , Monteiro, Álvaro N.A. , Antoniou, Antonis C. , Freedman, Matthew L., Coetzee, Gerhard A. , Gayther, Simon A. , Antonenkova, Natalia, Bean, Yukie T., Beckmann, Matthias W. , Bisogna, Maria, Bogdanova, Natalia , Brinton, Louise A. , Bruinsma, Fiona , Chang‐Claude, Jenny, Chen, Ann , Chen, Zhihua , Cunningham, Julie M. , Dansonka‐Mieszkowska, Agnieszka , Dicks, Ed , Dörk, Thilo , Eccles, Diana , Easton, Douglas F. , Edwards, Robert P., Eilber, Ursula, Ekici, Arif B. , Fasching, Peter A. , Gao, Yu‐Tang , Giles, Graham G. , Glasspool, Rosalind , Goode, Ellen L. , Grownwald, Jacek, Harrington, Patricia, Harter, Philipp , Hasmad, Hanis Nazihah, Hein, Alexander , Heitz, Florian , Hildebrandt, Michelle A.T., Hillemanns, Peter , Høgdall, Claus , Hosono, Satoyo , Iversen, Edwin S., Jakubowska, Anna , James, Paul A. , Jensen, Allan , Ji, Bu‐Tian , Kjær, Susanne K. , Kelemen, Linda E. , Kellar, Melissa, Kelley, Joseph L., Kiemeney, Lambertus A. , Krakstad, Camilla , Kupryjańczyk, Jolanta , Lambrechts, Diether , Lambrechts, Sandrina, Le, Nhu D. , Lele, Shashi, Leminen, Arto, Lester, Jenny, Levine, Douglas A. , Lissowska, Jolanta , Lu, Karen, Lubiński, Jan , Lundvall, Lene, Massuger, Leon F.A.G. , Matsuo, Keitaro , McGuire, Valerie , McLaughlin, John R., McNeish, Ian, Menon, Usha , Moysich, Kirsten B., Narod, Steven A., Nedergaard, Lotte , Ness, Roberta B., Azmi, Mat Adenan Noor, Odunsi, Kunle , Oršulić, Sandra , Pearce, Celeste Leigh, Pelttari, Liisa M. , Permuth‐Wey, Jennifer, Phelan, Catherine M., Pike, Malcolm C., Rossing, Mary Anne, Rothstein, Joseph H. , Runnebaum, Ingo B., Rzepecka, Iwona K. , Salvesen, Helga B., Schildkraut, Joellen M. , Schwaab, Ira, Sellers, Thomas A. , Shu, Xiao‐Ou, Shvetsov, Yurii B. , Sieh, Weiva , Song, Honglin , Southey, Melissa C. , Sucheston, Lara, Tangen, Ingvild L. , Teo, Soo‐Hwang , Thompson, Pamela J., Timorek, Agnieszka, Tworoger, Shelley S. , Altena, Anne M. van , Nieuwenhuysen, Els Van , Vergote, Ignace , Vierkant, Robert A. , Wang‐Gohrke, Shan , Walsh, Christine , Wentzensen, Nicolas, Whittemore, Alice S. , Wicklund, Kristine G. , Woo, Yin Ling , Wu, Xifeng , Wu, Anna H. , Lu, Karen H. , McNeish, Iain A. , Lambrechts, Diether , Tyrer, Jonathan P. , Couch, Fergus J. , Pharoah, Paul D.P. , Noushmehr, Houtan , Anton‐Culver, Hoda , Baker, Helen H. , Bandera, Elisa V. , Berchuck, Andrew , Bjørge, Line , Brooks‐Wilson, Angela , Bützow, Ralf C. , Campbell, Ian , Carty, Karen , Cook, Linda S. , Cramer, Daniel W. , Cybulski, Cezary , Dennis, Joe , Doherty, Jennifer A. , Bois, Andreas du , Dürst, Matthias , Fridley, Brooke L. , Gentry‐Maharaj, Aleksandra , Goodman, Marc T. , Hildebrandt, Michelle A.T. , Høgdall, Estrid , Karlan, Beth Y. , Lester, Jenny, Liang, Dong , Lu, Karen, McLaughlin, John R., McNeish, Ian, Modugno, Francesmary , Olson, Sara H. , Orlow, Irene , Weber, Rachel Palmieri , Pejovic, Tanja B. , Poole, Elizabeth M. , Risch, Harvey A. , Rosen, Barry P. , Rudolph, Anja , Siddiqui, Nadeem , Terry, Kathryn L. , Wentzensen, Nicolas , Wilkens, Lynne R. , Yang, Hannah , Zheng, Wei , Ziogas, Argyrios , Pelttari, L M , Dörk, Thilo , Lambrechts, Diether , Giles, Graham G , James, Paul , Kiemeney, Lambertus A , Kjaer, Susanne K , McNeish, Iain A , Ramus, Susan J , Teo, Soo H , Tworoger, Shelley S , Hein, Alexander , Hillemanns, Peter , Jensen, Allan , Vierkant, Robert A , Eccles, Diana , Menon, Usha , Lawrenson, Kate , Hazelett, Dennis J , Coetzee, Simon G , Monteiro, Alvaro N , Lissowska, Jolanta , Southey, Melissa C , Glasspool, Rosalind , Matsuo, Keitaro , Heitz, Florian , Jakubowska, Anna , Kupryjanczyk, Jolanta , Lambrechts, Diether , Sieh, Weiva , Ekici, Arif B , Bogdanova, Natalia V , Chenevix-Trench, Georgia , Drapkin, Ronny , Høgdall, Claus K , Lubinski, Jan
Human Molecular Genetics | March 24, 2015 | Volume: 24 | Issue: 13 | Pages: 3595-3607
Consortium analysis of gene and gene–folate interactions in purine and pyrimidine metabolism pathways with ovarian carcinoma risk
Kelemen, Linda E. , Terry, Kathryn L. , Goodman, Marc T. , Webb, Penelope M. , McGuire, Valerie , Rossing, Mary Anne, Wang, Qinggang , Dicks, Ed , Song, Honglin , Kupryjańczyk, Jolanta , Dansonka‐Mieszkowska, Agnieszka , Plisiecka-Hałasa, Joanna, Timorek, Agnieszka, Menon, Usha , Gayther, Simon A. , Ramus, Susan J. , Narod, Steven A., McLaughlin, John R., Glasspool, Rosalind , Lubiński, Jan , Jakubowska, Anna , Kiemeney, Lambertus A. , Massuger, Leon F.A.G. , Altena, Anne M. van , Aben, Katja K.H. , Olson, Sara H. , Orlow, Irene , Levine, Douglas A. , Bisogna, Maria, Southey, Melissa C. , Bruinsma, Fiona , Kjær, Susanne K. , Høgdall, Estrid , Jensen, Allan , Høgdall, Claus , Lundvall, Lene, Engelholm, Svend‐Aage, Harter, Philipp , Schwaab, Ira, Nevanlinna, Heli , Pelttari, Liisa M. , Leminen, Arto, Thompson, Pamela J., Lurie, Galina, Lambrechts, Diether , Nieuwenhuysen, Els Van , Lambrechts, Sandrina, Vergote, Ignace , Beesley, Jonathan, Investigators, AOCS Study Group/ACS, Fasching, Peter A. , Beckmann, Matthias W. , Hein, Alexander , Ekici, Arif B. , Wu, Anna H. , Pearce, Celeste Leigh, Pike, Malcolm C., Chang‐Claude, Jenny , Dörk, Thilo , Hillemanns, Peter , Runnebaum, Ingo B. , Bogdanova, Natalia , Antonenkova, Natalia, Odunsi, Kunle , Edwards, Robert P., Kelley, Joseph L., Ness, Roberta B., Walsh, Christine , Lester, Jenny, Oršulić, Sandra , Vierkant, Robert A. , Cunningham, Julie M. , Wu, Xifeng , Lu, Karen H., Hildebrandt, Michelle A.T., Weber, Rachel Palmieri , Iversen, Edwin S., Tworoger, Shelley S. , Salvesen, Helga B., Tangen, Ingvild L. , Bean, Yukie T., Kellar, Melissa, Wentzensen, Nicolas , Brinton, Louise A. , Lissowska, Jolanta , García‐Closas, Montserrat , Campbell, Ian , Eccles, Diana , Whittemore, Alice S. , Sieh, Weiva , Rothstein, Joseph H. , Phelan, Catherine M., Moysich, Kirsten B., Goode, Ellen L. , Schildkraut, Joellen M. , Sellers, Thomas A. , Le, Nhu D. , Lu, Karen H. , Zheng, Wei , Lambrechts, Diether , Bandera, Elisa V. , Tyrer, Jonathan P. , Gentry‐Maharaj, Aleksandra , Risch, Harvey A. , McLaughlin, John R., Siddiqui, Nadeem , Paul, James , Carty, Karen , Gronwald, Jacek , Cybulski, Cezary , Cramer, Daniel W. , Giles, Graham G. , Heitz, Florian , Bois, Andreas du , Bützow, Ralf C. , Wilkens, Lynne R. , Beesley, Jonathan, Investigators, AOCS Study Group/ACS, Doherty, Jennifer A. , Stram, Daniel O. , Rudolph, Anja , Dürst, Matthias , Modugno, Francesmary , Karlan, Beth Y. , Fridley, Brooke L. , Liang, Dong , Hildebrandt, Michelle A.T. , Poole, Elizabeth M. , Krakstad, Camilla , Bjørge, Line , Pejovic, Tanja B. , Anton‐Culver, Hoda , Ziogas, Argyrios , Berchuck, Andrew , Pharoah, Paul D.P. , Brooks‐Wilson, Angela , Cook, Linda S. , Pelttari, L M , Nevanlinna, H , Dörk, Thilo , Lambrechts, Diether , Kiemeney, Lambertus A , Kjaer, Susanne K , Ramus, Susan J , Tworoger, Shelley S , Webb, Penelope M , Hein, Alexander , Hillemanns, Peter , Jensen, Allan , Vierkant, Robert A , Eccles, Diana , Menon, Usha , Moysich, Kirsten , Orlow, Irene , Lissowska, Jolanta , Campbell, Ian G , Southey, Melissa C , Glasspool, Rosalind , Jakubowska, Anna , Kupryjanczyk, Jolanta , Lambrechts, Diether , Sieh, Weiva , García-Closas, Montserrat , Ekici, Arif B , Bogdanova, Natalia V , Zheng, Wei , Høgdall, Estrid , Høgdall, Claus K , Lubinski, Jan , Goodman, Marc T
Molecular Nutrition & Food Research | July 28, 2014 | Volume: 58 | Issue: 10 | Pages: 2023-2035
ScopeWe reevaluated previously reported associations between variants in pathways of one‐carbon (1‐C) (folate) transfer genes and ovarian carcinoma (OC) risk, and in related pathways of purine and pyrimidine metabolism, and assessed interactions with folate intake.Methods and resultsOdds ratios (OR) for 446 genetic variants were estimated among 13 410 OC cases and 22 635 controls, and among 2281 cases and 3444 controls with folate information. Following multiple testing correction, the most significant main effect associations were for dihydropyrimidine dehydrogenase (DPYD) variants rs11587873 (OR = 0.92; p = 6 × 10−5) and rs828054 (OR = 1.06; p = 1 × 10−4). Thirteen variants in the pyrimidine metabolism genes, DPYD, DPYS, PPAT, and TYMS, also interacted significantly with folate in a multivariant analysis (corrected p = 9.9 × 10−6) but collectively explained only 0.2% of OC risk. Although no other associations were significant after multiple testing correction, variants in SHMT1 in 1‐C transfer, previously reported with OC, suggested lower risk at higher folate (pinteraction = 0.03–0.006).ConclusionVariation in pyrimidine metabolism genes, particularly DPYD, which was previously reported to be associated with OC, may influence risk; however, stratification by folate intake is unlikely to modify disease risk appreciably in these women. SHMT1 SNP‐by‐folate interactions are plausible but require further validation. Polymorphisms in selected genes in purine metabolism were not associated with OC.