Author: "Kopperud R.K." - Searchworks@Jio Institute Digital Library Search Results

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1. Cross-Cancer Genome-Wide Association Study of Endometrial Cancer and Epithelial Ovarian Cancer Identifies Genetic Risk Regions Associated with Risk of Both Cancers.

Author: Glubb D.M., Thompson D.J., Aben K.K.H., Alsulimani A., Amant F., Annibali D., Attia J., Barricarte A., Beckmann M.W., Berchuck A., Bermisheva M., Bernardini M.Q., Bischof K., Bjorge L., Bodelon C., Brand A.H., Brenton J.D., Brinton L.A., Bruinsma F., Buchanan D.D., Burghaus S., Butzow R., Cai H., Carney M.E., Chanock S.J., Chen C., Chen X.Q., Chen Z., Cook L.S., Cunningham J.M., De Vivo I., deFazio A., Doherty J.A., Dork T., du Bois A., Dunning A.M., Durst M., Edwards T., Edwards R.P., Ekici A.B., Ewing A., Fasching P.A., Ferguson S., Flanagan J.M., Fostira F., Fountzilas G., Friedenreich C.M., Gao B., Gaudet M.M., Gawelko J., Gentry-Maharaj A., Giles G.G., Glasspool R., Goodman M.T., Gronwald J., Harris H.R., Harter P., Hein A., Heitz F., Hildebrandt M.A.T., Hillemanns P., Hogdall E., Hogdall C.K., Holliday E.G., Huntsman D.G., Huzarski T., Jakubowska A., Jensen A., Jones M.E., Karlan B.Y., Karnezis A., Kelley J.L., Khusnutdinova E., Killeen J.L., Kjaer S.K., Klapdor R., Kobel M., Konopka B., Konstantopoulou I., Kopperud R.K., Koti M., Kraft P., Kupryjanczyk J., Lambrechts D., Larson M.C., Le Marchand L., Lele S., Lester J., Li A.J., Liang D., Liebrich C., Lipworth L., Lissowska J., Lu L., Lu K.H., Macciotta A., Mattiello A., May T., McAlpine J.N., McGuire V., McNeish I.A., Menon U., Modugno F., Moysich K.B., Nevanlinna H., Odunsi K., Olsson H., Orsulic S., Osorio A., Palli D., Park-Simon T.-W., Pearce C.L., Pejovic T., Permuth J.B., Podgorska A., Ramus S.J., Rebbeck T.R., Riggan M.J., Risch H.A., Rothstein J.H., Runnebaum I.B., Scott R.J., Sellers T.A., Senz J., Setiawan V.W., Siddiqui N., Sieh W., Spiewankiewicz B., Sutphen R., Swerdlow A.J., Szafron L.M., Teo S.H., Thompson P.J., Thomsen L.C.V., Titus L., Tone A., Tumino R., Turman C., Vanderstichele A., Edwards D.V., Vergote I., Vierkant R.A., Wang Z., Wang-Gohrke S., Webb P.M., White E., Whittemore A.S., Winham S.J., Wu X., Wu A.H., Yannoukakos D., Spurdle A.B., O'Mara T.A., Glubb D.M., Thompson D.J., Aben K.K.H., Alsulimani A., Amant F., Annibali D., Attia J., Barricarte A., Beckmann M.W., Berchuck A., Bermisheva M., Bernardini M.Q., Bischof K., Bjorge L., Bodelon C., Brand A.H., Brenton J.D., Brinton L.A., Bruinsma F., Buchanan D.D., Burghaus S., Butzow R., Cai H., Carney M.E., Chanock S.J., Chen C., Chen X.Q., Chen Z., Cook L.S., Cunningham J.M., De Vivo I., deFazio A., Doherty J.A., Dork T., du Bois A., Dunning A.M., Durst M., Edwards T., Edwards R.P., Ekici A.B., Ewing A., Fasching P.A., Ferguson S., Flanagan J.M., Fostira F., Fountzilas G., Friedenreich C.M., Gao B., Gaudet M.M., Gawelko J., Gentry-Maharaj A., Giles G.G., Glasspool R., Goodman M.T., Gronwald J., Harris H.R., Harter P., Hein A., Heitz F., Hildebrandt M.A.T., Hillemanns P., Hogdall E., Hogdall C.K., Holliday E.G., Huntsman D.G., Huzarski T., Jakubowska A., Jensen A., Jones M.E., Karlan B.Y., Karnezis A., Kelley J.L., Khusnutdinova E., Killeen J.L., Kjaer S.K., Klapdor R., Kobel M., Konopka B., Konstantopoulou I., Kopperud R.K., Koti M., Kraft P., Kupryjanczyk J., Lambrechts D., Larson M.C., Le Marchand L., Lele S., Lester J., Li A.J., Liang D., Liebrich C., Lipworth L., Lissowska J., Lu L., Lu K.H., Macciotta A., Mattiello A., May T., McAlpine J.N., McGuire V., McNeish I.A., Menon U., Modugno F., Moysich K.B., Nevanlinna H., Odunsi K., Olsson H., Orsulic S., Osorio A., Palli D., Park-Simon T.-W., Pearce C.L., Pejovic T., Permuth J.B., Podgorska A., Ramus S.J., Rebbeck T.R., Riggan M.J., Risch H.A., Rothstein J.H., Runnebaum I.B., Scott R.J., Sellers T.A., Senz J., Setiawan V.W., Siddiqui N., Sieh W., Spiewankiewicz B., Sutphen R., Swerdlow A.J., Szafron L.M., Teo S.H., Thompson P.J., Thomsen L.C.V., Titus L., Tone A., Tumino R., Turman C., Vanderstichele A., Edwards D.V., Vergote I., Vierkant R.A., Wang Z., Wang-Gohrke S., Webb P.M., White E., Whittemore A.S., Winham S.J., Wu X., Wu A.H., Yannoukakos D., Spurdle A.B., and O'Mara T.A.
Abstract: BACKGROUND: Accumulating evidence suggests a relationship between endometrial cancer and ovarian cancer. Independent genome-wide association studies (GWAS) for endometrial cancer and ovarian cancer have identified 16 and 27 risk regions, respectively, four of which overlap between the two cancers. We aimed to identify joint endometrial and ovarian cancer risk loci by performing a meta-analysis of GWAS summary statistics from these two cancers. METHOD(S): Using LDScore regression, we explored the genetic correlation between endometrial cancer and ovarian cancer. To identify loci associated with the risk of both cancers, we implemented a pipeline of statistical genetic analyses (i.e., inverse-variance meta-analysis, colocalization, and M-values) and performed analyses stratified by subtype. Candidate target genes were then prioritized using functional genomic data. RESULT(S): Genetic correlation analysis revealed significant genetic correlation between the two cancers (rG = 0.43, P = 2.66 x 10-5). We found seven loci associated with risk for both cancers (PBonferroni < 2.4 x 10-9). In addition, four novel subgenome-wide regions at 7p22.2, 7q22.1, 9p12, and 11q13.3 were identified (P < 5 x 10-7). Promoter-associated HiChIP chromatin loops from immortalized endometrium and ovarian cell lines and expression quantitative trait loci data highlighted candidate target genes for further investigation. CONCLUSION(S): Using cross-cancer GWAS meta-analysis, we have identified several joint endometrial and ovarian cancer risk loci and candidate target genes for future functional analysis. IMPACT: Our research highlights the shared genetic relationship between endometrial cancer and ovarian cancer. Further studies in larger sample sets are required to confirm our findings.Copyright ©2020 American Association for Cancer Research.
Published: 2022

2. Cross-Cancer Genome-Wide Association Study of Endometrial Cancer and Epithelial Ovarian Cancer Identifies Genetic Risk Regions Associated with Risk of Both Cancers.

Author: Glubb D.M., Thompson D.J., Aben K.K.H., Alsulimani A., Amant F., Annibali D., Attia J., Barricarte A., Beckmann M.W., Berchuck A., Bermisheva M., Bernardini M.Q., Bischof K., Bjorge L., Bodelon C., Brand A.H., Brenton J.D., Brinton L.A., Bruinsma F., Buchanan D.D., Burghaus S., Butzow R., Cai H., Carney M.E., Chanock S.J., Chen C., Chen X.Q., Chen Z., Cook L.S., Cunningham J.M., De Vivo I., deFazio A., Doherty J.A., Dork T., du Bois A., Dunning A.M., Durst M., Edwards T., Edwards R.P., Ekici A.B., Ewing A., Fasching P.A., Ferguson S., Flanagan J.M., Fostira F., Fountzilas G., Friedenreich C.M., Gao B., Gaudet M.M., Gawelko J., Gentry-Maharaj A., Giles G.G., Glasspool R., Goodman M.T., Gronwald J., Harris H.R., Harter P., Hein A., Heitz F., Hildebrandt M.A.T., Hillemanns P., Hogdall E., Hogdall C.K., Holliday E.G., Huntsman D.G., Huzarski T., Jakubowska A., Jensen A., Jones M.E., Karlan B.Y., Karnezis A., Kelley J.L., Khusnutdinova E., Killeen J.L., Kjaer S.K., Klapdor R., Kobel M., Konopka B., Konstantopoulou I., Kopperud R.K., Koti M., Kraft P., Kupryjanczyk J., Lambrechts D., Larson M.C., Le Marchand L., Lele S., Lester J., Li A.J., Liang D., Liebrich C., Lipworth L., Lissowska J., Lu L., Lu K.H., Macciotta A., Mattiello A., May T., McAlpine J.N., McGuire V., McNeish I.A., Menon U., Modugno F., Moysich K.B., Nevanlinna H., Odunsi K., Olsson H., Orsulic S., Osorio A., Palli D., Park-Simon T.-W., Pearce C.L., Pejovic T., Permuth J.B., Podgorska A., Ramus S.J., Rebbeck T.R., Riggan M.J., Risch H.A., Rothstein J.H., Runnebaum I.B., Scott R.J., Sellers T.A., Senz J., Setiawan V.W., Siddiqui N., Sieh W., Spiewankiewicz B., Sutphen R., Swerdlow A.J., Szafron L.M., Teo S.H., Thompson P.J., Thomsen L.C.V., Titus L., Tone A., Tumino R., Turman C., Vanderstichele A., Edwards D.V., Vergote I., Vierkant R.A., Wang Z., Wang-Gohrke S., Webb P.M., White E., Whittemore A.S., Winham S.J., Wu X., Wu A.H., Yannoukakos D., Spurdle A.B., O'Mara T.A., Glubb D.M., Thompson D.J., Aben K.K.H., Alsulimani A., Amant F., Annibali D., Attia J., Barricarte A., Beckmann M.W., Berchuck A., Bermisheva M., Bernardini M.Q., Bischof K., Bjorge L., Bodelon C., Brand A.H., Brenton J.D., Brinton L.A., Bruinsma F., Buchanan D.D., Burghaus S., Butzow R., Cai H., Carney M.E., Chanock S.J., Chen C., Chen X.Q., Chen Z., Cook L.S., Cunningham J.M., De Vivo I., deFazio A., Doherty J.A., Dork T., du Bois A., Dunning A.M., Durst M., Edwards T., Edwards R.P., Ekici A.B., Ewing A., Fasching P.A., Ferguson S., Flanagan J.M., Fostira F., Fountzilas G., Friedenreich C.M., Gao B., Gaudet M.M., Gawelko J., Gentry-Maharaj A., Giles G.G., Glasspool R., Goodman M.T., Gronwald J., Harris H.R., Harter P., Hein A., Heitz F., Hildebrandt M.A.T., Hillemanns P., Hogdall E., Hogdall C.K., Holliday E.G., Huntsman D.G., Huzarski T., Jakubowska A., Jensen A., Jones M.E., Karlan B.Y., Karnezis A., Kelley J.L., Khusnutdinova E., Killeen J.L., Kjaer S.K., Klapdor R., Kobel M., Konopka B., Konstantopoulou I., Kopperud R.K., Koti M., Kraft P., Kupryjanczyk J., Lambrechts D., Larson M.C., Le Marchand L., Lele S., Lester J., Li A.J., Liang D., Liebrich C., Lipworth L., Lissowska J., Lu L., Lu K.H., Macciotta A., Mattiello A., May T., McAlpine J.N., McGuire V., McNeish I.A., Menon U., Modugno F., Moysich K.B., Nevanlinna H., Odunsi K., Olsson H., Orsulic S., Osorio A., Palli D., Park-Simon T.-W., Pearce C.L., Pejovic T., Permuth J.B., Podgorska A., Ramus S.J., Rebbeck T.R., Riggan M.J., Risch H.A., Rothstein J.H., Runnebaum I.B., Scott R.J., Sellers T.A., Senz J., Setiawan V.W., Siddiqui N., Sieh W., Spiewankiewicz B., Sutphen R., Swerdlow A.J., Szafron L.M., Teo S.H., Thompson P.J., Thomsen L.C.V., Titus L., Tone A., Tumino R., Turman C., Vanderstichele A., Edwards D.V., Vergote I., Vierkant R.A., Wang Z., Wang-Gohrke S., Webb P.M., White E., Whittemore A.S., Winham S.J., Wu X., Wu A.H., Yannoukakos D., Spurdle A.B., and O'Mara T.A.
Abstract: BACKGROUND: Accumulating evidence suggests a relationship between endometrial cancer and ovarian cancer. Independent genome-wide association studies (GWAS) for endometrial cancer and ovarian cancer have identified 16 and 27 risk regions, respectively, four of which overlap between the two cancers. We aimed to identify joint endometrial and ovarian cancer risk loci by performing a meta-analysis of GWAS summary statistics from these two cancers. METHOD(S): Using LDScore regression, we explored the genetic correlation between endometrial cancer and ovarian cancer. To identify loci associated with the risk of both cancers, we implemented a pipeline of statistical genetic analyses (i.e., inverse-variance meta-analysis, colocalization, and M-values) and performed analyses stratified by subtype. Candidate target genes were then prioritized using functional genomic data. RESULT(S): Genetic correlation analysis revealed significant genetic correlation between the two cancers (rG = 0.43, P = 2.66 x 10-5). We found seven loci associated with risk for both cancers (PBonferroni < 2.4 x 10-9). In addition, four novel subgenome-wide regions at 7p22.2, 7q22.1, 9p12, and 11q13.3 were identified (P < 5 x 10-7). Promoter-associated HiChIP chromatin loops from immortalized endometrium and ovarian cell lines and expression quantitative trait loci data highlighted candidate target genes for further investigation. CONCLUSION(S): Using cross-cancer GWAS meta-analysis, we have identified several joint endometrial and ovarian cancer risk loci and candidate target genes for future functional analysis. IMPACT: Our research highlights the shared genetic relationship between endometrial cancer and ovarian cancer. Further studies in larger sample sets are required to confirm our findings.Copyright ©2020 American Association for Cancer Research.
Published: 2022

3. Expression of L1CAM in curettage or high L1CAM level in preoperative blood samples predicts lymph node metastases and poor outcome in endometrial cancer patients

Author: Tangen, I.L., Kopperud, R.K., Visser, N.C.M., Staff, A.C., Tingulstad, S., Marcickiewicz, J., Amant, F., Bjorge, L., Pijnenborg, J.M.A., Salvesen, H.B., Werner, H.M., Trovik, J., Krakstad, C., Tangen, I.L., Kopperud, R.K., Visser, N.C.M., Staff, A.C., Tingulstad, S., Marcickiewicz, J., Amant, F., Bjorge, L., Pijnenborg, J.M.A., Salvesen, H.B., Werner, H.M., Trovik, J., and Krakstad, C.
Abstract: Item does not contain fulltext, BACKGROUND: Several studies have identified L1 cell adhesion molecule (L1CAM) as a strong prognostic marker in endometrial cancer. To further underline the clinical usefulness of this biomarker, we investigated L1CAM as a predictive marker for lymph node metastases and its prognostic impact in curettage specimens and preoperative plasma samples. In addition, we aimed to validate the prognostic value of L1CAM in hysterectomy specimen. METHODS: Immunohistochemical staining of L1CAM was performed for 795 hysterectomy and 1134 curettage specimen from endometrial cancer patients. The L1CAM level in preoperative blood samples from 372 patients was determined using ELISA. RESULTS: Expression of L1CAM in curettage specimen was significantly correlated to L1CAM level in corresponding hysterectomy specimen (P<0.001). Both in curettage and preoperative plasma samples L1CAM upregulation was significantly associated with features of aggressive disease and poor outcome (P<0.001). The L1CAM was an independent predictor of lymph node metastases, after correction for curettage histology, both in curettage specimen (P=0.002) and plasma samples (P=0.048). In the hysterectomy samples L1CAM was significantly associated with poor outcome (P<0.001). CONCLUSIONS: We demonstrate that preoperative evaluation of L1CAM levels, both in curettage or plasma samples, predicts lymph node metastases and adds valuable information on patient prognosis.
Published: 2017

4. Identification of 12 new susceptibility loci for different histotypes of epithelial ovarian cancer

Author: Phelan, C. (Catherine), Kuchenbaecker, K.B. (Karoline), Tyrer, J.P. (Jonathan P.), Kar, S.P. (Siddhartha P.), Lawrenson, K. (Kate), Winham, S.J. (Stacey J.), Dennis, J. (Joe), Pirie, A. (Ailith), Riggan, M.J. (Marjorie J.), Chornokur, G. (Ganna), Earp, M.A. (Madalene A.), Lyra, P.C. (Paulo C.), Lee, J.M. (Janet M.), Coetzee, S. (Simon), Beesley, J. (Jonathan), McGuffog, L. (Lesley), Soucy, P. (Penny), Dicks, E. (Ed), Lee, A. (Andrew), Barrowdale, D. (Daniel), Lecarpentier, J. (Julie), Leslie, G. (Goska), Aalfs, C.M. (Cora), Aben, K.K.H. (Katja), Adams, M. (Marcia), Adlard, J.W. (Julian), Andrulis, I.L. (Irene), Anton-Culver, H. (Hoda), Antonenkova, N. (Natalia), Aravantinos, G. (Gerasimos), Arnold, N. (Norbert), Arun, B.K. (Banu), Arver, B. (Brita), Azzollini, J., Balmana, J. (Judith), Banerjee, S. (Susana), Barjhoux, L. (Laure), Barkardottir, R.B. (Rosa B.), Bean, Y. (Yukie), Beckmann, M.W. (Matthias), Beeghly-Fadiel, A. (Alicia), Benítez, J. (Javier), Bermisheva, M. (Marina), Bernardini, M.Q. (Marcus Q.), Birrer, M.J. (Michael J.), Bjorge, L. (Line), Black, A., Blankstein, K. (Kenneth), Blok, M.J. (Marinus), Bodelon, C. (Clara), Bogdanova, N. (Natalia), Bojesen, A. (Anders), Bonanni, B. (Bernardo), Borg, Å. (Åke), Bradbury, A.R. (Angela R.), Brenton, J.D. (James D.), Brewer, C. (Carole), Brinton, L.A. (Louise), Broberg, P. (Per), Brooks-Wilson, A. (Angela), Bruinsma, F. (Fiona), Brunet, J. (Joan), Buecher, B. (Bruno), Butzow, R. (Ralf), Buys, S.S. (Saundra), Caldes, T. (Trinidad), Caligo, M.A. (Maria A.), Campbell, I. (Ian), Cannioto, R. (Rikki), Carney, M.E. (Michael), Cescon, T. (Terence), Chan, S. (Salina), Chang-Claude, J. (Jenny), Chanock, S.J. (Stephen), Chen, X.Q. (Xiao Qing), Chiew, Y.-E. (Yoke-Eng), Chiquette, J. (Jocelyne), Chung, W. (Wendy), Claes, K. (Kathleen), Conner, T. (Thomas), Cook, L.S. (Linda S.), Cook, J. (Jackie), Cramer, D.W. (Daniel), Cunningham, J.M. (Julie), D'Aloisio, A.A. (Aimee A.), Daly, M.B. (Mary), Damiola, F. (Francesca), Damirovna, S.D. (Sakaeva Dina), Dansonka-Mieszkowska, A. (Agnieszka), Dao, F. (Fanny), Davidson, R. (Rosemarie), DeFazio, A. (Anna), Delnatte, C.D. (Capucine), Doheny, K.F. (Kimberly), Díez, O. (Orland), Ding, Y.C. (Yuan Chun), Doherty, J.A. (Jennifer), Domchek, S.M. (Susan), Dorfling, C.M. (Cecilia), Dörk, T. (Thilo), Dossus, L. (Laure), Duran, M. (Mercedes), Dürst, M. (Matthias), Dworniczak, B. (Bernd), Eccles, D. (Diana), Edwards, T. (Todd), Eeles, R. (Rosalind), Eilber, U. (Ursula), Ejlertsen, B. (Bent), Ekici, A.B. (Arif), Ellis, S. (Steve), Elvira, M. (Mingajeva), Eng, K.H. (Kevin H.), Engel, C. (Christoph), Evans, D.G. (Gareth), Fasching, P.A. (Peter), Ferguson, S. (Sarah), Ferrer, S.F., Flanagan, J.M. (James), Fogarty, Z.C. (Zachary C.), Fortner, R.T. (Renée T.), Fostira, F. (Florentia), Foulkes, W.D. (William D.), Fountzilas, G. (George), Fridley, B.L. (Brooke), Friebel, M.O.W. (Mark ), Friedman, E. (Eitan), Frost, D. (Debra), Ganz, P.A. (Patricia), Garber, J. (Judy), García, M.J. (María J.), Garcia-Barberan, V. (Vanesa), Gehrig, P.A. (Paola A.), Gentry-Maharaj, A. (Aleksandra), Gerdes, A-M. (Anne-Marie), Giles, G.G. (Graham G.), Glasspool, R. (Rosalind), Glendon, G. (Gord), Godwin, A.K. (Andrew K.), Radice, P. (Paolo), Goranova, T. (Teodora), Gore, M. (Martin), Greene, M.H. (Mark H.), Gronwald, J. (Jacek), Gruber, S.B. (Stephen), Hahnen, E. (Eric), Haiman, C.A. (Christopher), Håkansson, N. (Niclas), Hamann, U. (Ute), Hansen, T.V.O. (Thomas V.O.), Harrington, P.A. (Patricia A.), Harris, H.R. (Holly), Hauke, J. (Jan), Hein, A. (Alexander), Henderson, A. (Alex), Hildebrandt, M.A.T. (Michelle A.T.), Hillemanns, P. (Peter), Hodgson, S. (Shirley), Høgdall, C.K. (Claus), Høgdall, E. (Estrid), Hogervorst, F.B.L. (Frans B. L.), Holland, H. (Helene), Hooning, M.J. (Maartje J.), Hosking, K. (Karen), Huang, R.-Y. (Ruea-Yea), Hulick, P.J. (Peter), Hung, J. (Jillian), Hunter, D.J. (David J.), Huntsman, D.G. (David G.), Huzarski, T. (Tomasz), Imyanitov, E.N. (Evgeny), Isaacs, C. (Claudine), Iversen, E. (Erik), Izatt, L. (Louise), Izquierdo, A. (A.), Jakubowska, A. (Anna), James, P. (Paul), Janavicius, R. (Ramunas), Jernetz, M. (Mats), Jensen, A. (Allan), Jensen, U.B., John, E.M. (Esther), Johnatty, S.E. (Sharon), Jones, M.E. (Michael E.), Kannisto, P. (Päivi), Karlan, B.Y. (Beth), Karnezis, A. (Anthony), Kast, K. (Karin), Kennedy, C.J. (Catherine J.), Khusnutdinova, E.K. (Elza), Kiemeney, L.A.L.M. (Bart), Kiiski, J.I. (Johanna I.), Kim, S.-W. (Sung-Won), Kjaer, M. (Michael), Köbel, M. (Martin), Kopperud, R.K. (Reidun K.), Kruse, T.A. (Torben), Kupryjanczyk, J. (Jolanta), Kwong, A. (Ava), Laitman, Y. (Yael), Lambrechts, D. (Diether), Larrañaga, N. (Nerea), Larson, M.C. (Melissa), Lazaro, C. (Conxi), Le, N.D. (Nhu D.), Le Marchand, L. (Loic), Lee, J.W. (Jong Won), Lele, S.B. (Shashikant B.), Leminen, A. (Arto), Leroux, D. (Dominique), Lester, J. (Jenny), Lesueur, F. (Fabienne), Levine, D.A. (Douglas), Liang, D. (Dong), Liebrich, C. (Clemens), Lilyquist, J. (Jenna), Lipworth, L. (Loren), Lissowska, J. (Jolanta), Lu, K.H. (Karen), Lubinski, J. (Jan), Luccarini, C. (Craig), Lundvall, L. (Lene), Mai, P.L. (Phuong), Mendoza-Fandiño, G. (Gustavo), Manoukian, S. (Siranoush), Massuger, L.F. (Leon), May, T. (Taymaa), Mazoyer, S. (Sylvie), McAlpine, J.N. (Jessica N.), McGuire, V. (Valerie), McLaughlin, J. (John), McNeish, I. (Iain), Meijers-Heijboer, E.J. (Hanne), Meindl, A. (Alfons), Menon, U. (Usha), Mensenkamp, A.R. (Arjen R.), Merritt, M.A. (Melissa A.), Milne, R.L. (Roger), Mitchell, G. (Gillian), Modugno, F. (Francesmary), Moes-Sosnowska, J. (Joanna), Moffitt, M. (Melissa), Montagna, M. (Marco), Moysich, K.B. (Kirsten), Mulligan, A.M. (Anna Marie), Musinsky, J. (Jacob), Nathanson, K.L. (Katherine), Nedergaard, L. (Lotte), Ness, R.B. (Roberta), Neuhausen, S.L. (Susan), Nevanlinna, H. (Heli), Niederacher, D. (Dieter), Nussbaum, R. (Robert), Odunsi, K. (Kunle), Olah, E. (Edith), Olopade, O.I. (Olofunmilayo), Olsson, H. (Håkan), Olswold, C. (Curtis), O'Malley, D.M. (David M.), Ong, K.-R. (Kai-Ren), Onland-Moret, N.C. (Charlotte), Orr, N. (Nick), Orsulic, S. (Sandra), Osorio, A. (Ana), Palli, D. (Domenico), Papi, L. (Laura), Park-Simon, T.-W., Paul, J. (James), Pearce, C.L. (Celeste), Pedersen, I.S. (Inge Søkilde), Peeters, P.H.M., Peissel, B. (Bernard), Peixoto, A. (Ana), Pejovic, T. (Tanja), Pelttari, L.M. (Liisa M.), Permuth, J.B. (Jennifer B.), Peterlongo, P. (Paolo), Pezzani, L. (Lidia), Pfeiler, G. (Georg), Phillips, K.-A. (Kelly-Anne), Piedmonte, M. (Marion), Pike, M.C. (Malcolm), Piskorz, A.M. (Anna M.), Poblete, S.R. (Samantha R.), Pócza, T. (Tímea), Poole, E.M. (Elizabeth M.), Poppe, B. (Bruce), Porteous, M.E. (Mary), Prieur, F. (Fabienne), Prokofyeva, D. (Darya), Pugh, E. (Elizabeth), Pujana, M.A. (Miquel Angel), Pujol, P. (Pascal), Rantala, J. (Johanna), Rappaport-Fuerhauser, C. (Christine), Rennert, G. (Gad), Rhiem, K. (Kerstin), Rice, P. (Patricia), Richardson, A.L. (Andrea), Robson, M. (Mark), Rodriguez, G.C. (Gustavo), Rodríguez-Antona, C. (Cristina), Romm, J. (Jane), Rookus, M.A. (Matti), Rossing, M.A. (Mary Anne), Rothstein, J.H. (Joseph H.), Rudolph, A. (Anja), Runnebaum, I.B. (Ingo), Salvesen, H.B. (Helga), Sandler, D.P. (Dale P.), Schoemaker, M.J. (Minouk J.), Senter, L. (Leigha), Setiawan, V.W. (V. Wendy), Severi, G. (Gianluca), Sharma, P. (Priyanka), Shelford, T. (Tameka), Siddiqui, N. (Nadeem), Side, L. (Lucy), Sieh, W. (Weiva), Singer, C.F. (Christian), Sobol, H. (Hagay), Song, H. (Honglin), Southey, M.C. (Melissa), Spurdle, A.B. (Amanda), Stadler, Z. (Zsofia), Steinemann, D. (Doris), Stoppa-Lyonnet, D. (Dominique), Sucheston-Campbell, L.E. (Lara E.), Sukiennicki, G. (Grzegorz), Sutphen, R. (Rebecca), Sutter, C. (Christian), Swerdlow, A.J. (Anthony ), Szabo, C. (Csilla), Szafron, L. (Lukasz), Tan, Y.Y. (Yen Y.), Taylor, J.A. (Jack A.), Tea, M.-K., Teixeira, P.J., Teo, S.-H. (Soo-Hwang), Terry, K.L. (Kathryn L.), Thompson, P.J. (Pamela J.), Thomsen, L.C.V. (Liv Cecilie Vestrheim), Thull, D.L. (Darcy L.), Tihomirova, L. (Laima), Tinker, A.V. (Anna V.), Tischkowitz, M. (Marc), Tognazzo, S. (Silvia), Toland, A.E. (Amanda Ewart), Tone, A. (Alicia), Trabert, B. (Britton), Travis, S.P.L. (Simon), Trichopoulou, A. (Antonia), Tung, N. (Nadine), Tworoger, S. (Shelley), Van Altena, A.M. (Anne M.), Van Den Berg, D. (David), Van Der Hout, A.H. (Annemarie H.), Luijt, R.B. (Rob) van der, Van Heetvelde, M. (Mattias), Van Nieuwenhuysen, E. (Els), Rensburg, E.J. (Elizabeth) van, Vanderstichele, A. (Adriaan), Varon-Mateeva, R. (Raymonda), Vega, A. (Ana), Edwards, D.V. (Digna Velez), Vergote, I., Vierkant, R.A. (Robert), Vijai, J. (Joseph), Vratimos, A. (Athanassios), Walker, L.J. (Lisa), Walsh, C. (Christine), Wand, D. (Dorothea), Wang-Gohrke, S. (Shan), Wappenschmidt, B. (Barbara), Webb, P.M. (Penelope M.), Weinberg, C.R. (Clarice R.), Weitzel, J.N. (Jeffrey), Wentzensen, N. (N.), Whittemore, A.S. (Alice), Wijnen, J.T. (Juul), Wilkens, L.R. (Lynne), Wolk, K. (Kerstin), Woo, M. (Michelle), Wu, X. (Xifeng), Wu, A.H. (Anna), Yang, H.P. (Hannah), Yannoukakos, D. (Drakoulis), Ziogas, A. (Argyrios), Zorn, K.K. (Kristin K.), Narod, S.A. (Steven A.), Easton, D.F. (Douglas), Amos, W., Schildkraut, J.M. (Joellen), Ramus, S.J. (Susan), Ottini, L. (Laura), Goodman, M.T. (Marc), Park, S.K. (Sue K.), Kelemen, L.E. (Linda), Risch, H. (Harvey), Thomassen, M. (Mads), Offit, K. (Kenneth), Simard, J. (Jacques), Schmutzler, R.K. (Rita), Hazelett, D. (Dennis), Monteiro, A.N.A. (Alvaro N.), Couch, F.J. (Fergus), Berchuck, A. (Andrew), Chenevix-Trench, G. (Georgia), Goode, E.L. (Ellen), Sellers, T.F., Gayther, S.A. (Simon), Antoniou, A.C. (Antonis), Pharoah, P.D.P. (Paul), Phelan, C. (Catherine), Kuchenbaecker, K.B. (Karoline), Tyrer, J.P. (Jonathan P.), Kar, S.P. (Siddhartha P.), Lawrenson, K. (Kate), Winham, S.J. (Stacey J.), Dennis, J. (Joe), Pirie, A. (Ailith), Riggan, M.J. (Marjorie J.), Chornokur, G. (Ganna), Earp, M.A. (Madalene A.), Lyra, P.C. (Paulo C.), Lee, J.M. (Janet M.), Coetzee, S. (Simon), Beesley, J. (Jonathan), McGuffog, L. (Lesley), Soucy, P. (Penny), Dicks, E. (Ed), Lee, A. (Andrew), Barrowdale, D. (Daniel), Lecarpentier, J. (Julie), Leslie, G. (Goska), Aalfs, C.M. (Cora), Aben, K.K.H. (Katja), Adams, M. (Marcia), Adlard, J.W. (Julian), Andrulis, I.L. (Irene), Anton-Culver, H. (Hoda), Antonenkova, N. (Natalia), Aravantinos, G. (Gerasimos), Arnold, N. (Norbert), Arun, B.K. (Banu), Arver, B. (Brita), Azzollini, J., Balmana, J. (Judith), Banerjee, S. (Susana), Barjhoux, L. (Laure), Barkardottir, R.B. (Rosa B.), Bean, Y. (Yukie), Beckmann, M.W. (Matthias), Beeghly-Fadiel, A. (Alicia), Benítez, J. (Javier), Bermisheva, M. (Marina), Bernardini, M.Q. (Marcus Q.), Birrer, M.J. (Michael J.), Bjorge, L. (Line), Black, A., Blankstein, K. (Kenneth), Blok, M.J. (Marinus), Bodelon, C. (Clara), Bogdanova, N. (Natalia), Bojesen, A. (Anders), Bonanni, B. (Bernardo), Borg, Å. (Åke), Bradbury, A.R. (Angela R.), Brenton, J.D. (James D.), Brewer, C. (Carole), Brinton, L.A. (Louise), Broberg, P. (Per), Brooks-Wilson, A. (Angela), Bruinsma, F. (Fiona), Brunet, J. (Joan), Buecher, B. (Bruno), Butzow, R. (Ralf), Buys, S.S. (Saundra), Caldes, T. (Trinidad), Caligo, M.A. (Maria A.), Campbell, I. (Ian), Cannioto, R. (Rikki), Carney, M.E. (Michael), Cescon, T. (Terence), Chan, S. (Salina), Chang-Claude, J. (Jenny), Chanock, S.J. (Stephen), Chen, X.Q. (Xiao Qing), Chiew, Y.-E. (Yoke-Eng), Chiquette, J. (Jocelyne), Chung, W. (Wendy), Claes, K. (Kathleen), Conner, T. (Thomas), Cook, L.S. (Linda S.), Cook, J. (Jackie), Cramer, D.W. (Daniel), Cunningham, J.M. (Julie), D'Aloisio, A.A. (Aimee A.), Daly, M.B. (Mary), Damiola, F. (Francesca), Damirovna, S.D. (Sakaeva Dina), Dansonka-Mieszkowska, A. (Agnieszka), Dao, F. (Fanny), Davidson, R. (Rosemarie), DeFazio, A. (Anna), Delnatte, C.D. (Capucine), Doheny, K.F. (Kimberly), Díez, O. (Orland), Ding, Y.C. (Yuan Chun), Doherty, J.A. (Jennifer), Domchek, S.M. (Susan), Dorfling, C.M. (Cecilia), Dörk, T. (Thilo), Dossus, L. (Laure), Duran, M. (Mercedes), Dürst, M. (Matthias), Dworniczak, B. (Bernd), Eccles, D. (Diana), Edwards, T. (Todd), Eeles, R. (Rosalind), Eilber, U. (Ursula), Ejlertsen, B. (Bent), Ekici, A.B. (Arif), Ellis, S. (Steve), Elvira, M. (Mingajeva), Eng, K.H. (Kevin H.), Engel, C. (Christoph), Evans, D.G. (Gareth), Fasching, P.A. (Peter), Ferguson, S. (Sarah), Ferrer, S.F., Flanagan, J.M. (James), Fogarty, Z.C. (Zachary C.), Fortner, R.T. (Renée T.), Fostira, F. (Florentia), Foulkes, W.D. (William D.), Fountzilas, G. (George), Fridley, B.L. (Brooke), Friebel, M.O.W. (Mark ), Friedman, E. (Eitan), Frost, D. (Debra), Ganz, P.A. (Patricia), Garber, J. (Judy), García, M.J. (María J.), Garcia-Barberan, V. (Vanesa), Gehrig, P.A. (Paola A.), Gentry-Maharaj, A. (Aleksandra), Gerdes, A-M. (Anne-Marie), Giles, G.G. (Graham G.), Glasspool, R. (Rosalind), Glendon, G. (Gord), Godwin, A.K. (Andrew K.), Radice, P. (Paolo), Goranova, T. (Teodora), Gore, M. (Martin), Greene, M.H. (Mark H.), Gronwald, J. (Jacek), Gruber, S.B. (Stephen), Hahnen, E. (Eric), Haiman, C.A. (Christopher), Håkansson, N. (Niclas), Hamann, U. (Ute), Hansen, T.V.O. (Thomas V.O.), Harrington, P.A. (Patricia A.), Harris, H.R. (Holly), Hauke, J. (Jan), Hein, A. (Alexander), Henderson, A. (Alex), Hildebrandt, M.A.T. (Michelle A.T.), Hillemanns, P. (Peter), Hodgson, S. (Shirley), Høgdall, C.K. (Claus), Høgdall, E. (Estrid), Hogervorst, F.B.L. (Frans B. L.), Holland, H. (Helene), Hooning, M.J. (Maartje J.), Hosking, K. (Karen), Huang, R.-Y. (Ruea-Yea), Hulick, P.J. (Peter), Hung, J. (Jillian), Hunter, D.J. (David J.), Huntsman, D.G. (David G.), Huzarski, T. (Tomasz), Imyanitov, E.N. (Evgeny), Isaacs, C. (Claudine), Iversen, E. (Erik), Izatt, L. (Louise), Izquierdo, A. (A.), Jakubowska, A. (Anna), James, P. (Paul), Janavicius, R. (Ramunas), Jernetz, M. (Mats), Jensen, A. (Allan), Jensen, U.B., John, E.M. (Esther), Johnatty, S.E. (Sharon), Jones, M.E. (Michael E.), Kannisto, P. (Päivi), Karlan, B.Y. (Beth), Karnezis, A. (Anthony), Kast, K. (Karin), Kennedy, C.J. (Catherine J.), Khusnutdinova, E.K. (Elza), Kiemeney, L.A.L.M. (Bart), Kiiski, J.I. (Johanna I.), Kim, S.-W. (Sung-Won), Kjaer, M. (Michael), Köbel, M. (Martin), Kopperud, R.K. (Reidun K.), Kruse, T.A. (Torben), Kupryjanczyk, J. (Jolanta), Kwong, A. (Ava), Laitman, Y. (Yael), Lambrechts, D. (Diether), Larrañaga, N. (Nerea), Larson, M.C. (Melissa), Lazaro, C. (Conxi), Le, N.D. (Nhu D.), Le Marchand, L. (Loic), Lee, J.W. (Jong Won), Lele, S.B. (Shashikant B.), Leminen, A. (Arto), Leroux, D. (Dominique), Lester, J. (Jenny), Lesueur, F. (Fabienne), Levine, D.A. (Douglas), Liang, D. (Dong), Liebrich, C. (Clemens), Lilyquist, J. (Jenna), Lipworth, L. (Loren), Lissowska, J. (Jolanta), Lu, K.H. (Karen), Lubinski, J. (Jan), Luccarini, C. (Craig), Lundvall, L. (Lene), Mai, P.L. (Phuong), Mendoza-Fandiño, G. (Gustavo), Manoukian, S. (Siranoush), Massuger, L.F. (Leon), May, T. (Taymaa), Mazoyer, S. (Sylvie), McAlpine, J.N. (Jessica N.), McGuire, V. (Valerie), McLaughlin, J. (John), McNeish, I. (Iain), Meijers-Heijboer, E.J. (Hanne), Meindl, A. (Alfons), Menon, U. (Usha), Mensenkamp, A.R. (Arjen R.), Merritt, M.A. (Melissa A.), Milne, R.L. (Roger), Mitchell, G. (Gillian), Modugno, F. (Francesmary), Moes-Sosnowska, J. (Joanna), Moffitt, M. (Melissa), Montagna, M. (Marco), Moysich, K.B. (Kirsten), Mulligan, A.M. (Anna Marie), Musinsky, J. (Jacob), Nathanson, K.L. (Katherine), Nedergaard, L. (Lotte), Ness, R.B. (Roberta), Neuhausen, S.L. (Susan), Nevanlinna, H. (Heli), Niederacher, D. (Dieter), Nussbaum, R. (Robert), Odunsi, K. (Kunle), Olah, E. (Edith), Olopade, O.I. (Olofunmilayo), Olsson, H. (Håkan), Olswold, C. (Curtis), O'Malley, D.M. (David M.), Ong, K.-R. (Kai-Ren), Onland-Moret, N.C. (Charlotte), Orr, N. (Nick), Orsulic, S. (Sandra), Osorio, A. (Ana), Palli, D. (Domenico), Papi, L. (Laura), Park-Simon, T.-W., Paul, J. (James), Pearce, C.L. (Celeste), Pedersen, I.S. (Inge Søkilde), Peeters, P.H.M., Peissel, B. (Bernard), Peixoto, A. (Ana), Pejovic, T. (Tanja), Pelttari, L.M. (Liisa M.), Permuth, J.B. (Jennifer B.), Peterlongo, P. (Paolo), Pezzani, L. (Lidia), Pfeiler, G. (Georg), Phillips, K.-A. (Kelly-Anne), Piedmonte, M. (Marion), Pike, M.C. (Malcolm), Piskorz, A.M. (Anna M.), Poblete, S.R. (Samantha R.), Pócza, T. (Tímea), Poole, E.M. (Elizabeth M.), Poppe, B. (Bruce), Porteous, M.E. (Mary), Prieur, F. (Fabienne), Prokofyeva, D. (Darya), Pugh, E. (Elizabeth), Pujana, M.A. (Miquel Angel), Pujol, P. (Pascal), Rantala, J. (Johanna), Rappaport-Fuerhauser, C. (Christine), Rennert, G. (Gad), Rhiem, K. (Kerstin), Rice, P. (Patricia), Richardson, A.L. (Andrea), Robson, M. (Mark), Rodriguez, G.C. (Gustavo), Rodríguez-Antona, C. (Cristina), Romm, J. (Jane), Rookus, M.A. (Matti), Rossing, M.A. (Mary Anne), Rothstein, J.H. (Joseph H.), Rudolph, A. (Anja), Runnebaum, I.B. (Ingo), Salvesen, H.B. (Helga), Sandler, D.P. (Dale P.), Schoemaker, M.J. (Minouk J.), Senter, L. (Leigha), Setiawan, V.W. (V. Wendy), Severi, G. (Gianluca), Sharma, P. (Priyanka), Shelford, T. (Tameka), Siddiqui, N. (Nadeem), Side, L. (Lucy), Sieh, W. (Weiva), Singer, C.F. (Christian), Sobol, H. (Hagay), Song, H. (Honglin), Southey, M.C. (Melissa), Spurdle, A.B. (Amanda), Stadler, Z. (Zsofia), Steinemann, D. (Doris), Stoppa-Lyonnet, D. (Dominique), Sucheston-Campbell, L.E. (Lara E.), Sukiennicki, G. (Grzegorz), Sutphen, R. (Rebecca), Sutter, C. (Christian), Swerdlow, A.J. (Anthony ), Szabo, C. (Csilla), Szafron, L. (Lukasz), Tan, Y.Y. (Yen Y.), Taylor, J.A. (Jack A.), Tea, M.-K., Teixeira, P.J., Teo, S.-H. (Soo-Hwang), Terry, K.L. (Kathryn L.), Thompson, P.J. (Pamela J.), Thomsen, L.C.V. (Liv Cecilie Vestrheim), Thull, D.L. (Darcy L.), Tihomirova, L. (Laima), Tinker, A.V. (Anna V.), Tischkowitz, M. (Marc), Tognazzo, S. (Silvia), Toland, A.E. (Amanda Ewart), Tone, A. (Alicia), Trabert, B. (Britton), Travis, S.P.L. (Simon), Trichopoulou, A. (Antonia), Tung, N. (Nadine), Tworoger, S. (Shelley), Van Altena, A.M. (Anne M.), Van Den Berg, D. (David), Van Der Hout, A.H. (Annemarie H.), Luijt, R.B. (Rob) van der, Van Heetvelde, M. (Mattias), Van Nieuwenhuysen, E. (Els), Rensburg, E.J. (Elizabeth) van, Vanderstichele, A. (Adriaan), Varon-Mateeva, R. (Raymonda), Vega, A. (Ana), Edwards, D.V. (Digna Velez), Vergote, I., Vierkant, R.A. (Robert), Vijai, J. (Joseph), Vratimos, A. (Athanassios), Walker, L.J. (Lisa), Walsh, C. (Christine), Wand, D. (Dorothea), Wang-Gohrke, S. (Shan), Wappenschmidt, B. (Barbara), Webb, P.M. (Penelope M.), Weinberg, C.R. (Clarice R.), Weitzel, J.N. (Jeffrey), Wentzensen, N. (N.), Whittemore, A.S. (Alice), Wijnen, J.T. (Juul), Wilkens, L.R. (Lynne), Wolk, K. (Kerstin), Woo, M. (Michelle), Wu, X. (Xifeng), Wu, A.H. (Anna), Yang, H.P. (Hannah), Yannoukakos, D. (Drakoulis), Ziogas, A. (Argyrios), Zorn, K.K. (Kristin K.), Narod, S.A. (Steven A.), Easton, D.F. (Douglas), Amos, W., Schildkraut, J.M. (Joellen), Ramus, S.J. (Susan), Ottini, L. (Laura), Goodman, M.T. (Marc), Park, S.K. (Sue K.), Kelemen, L.E. (Linda), Risch, H. (Harvey), Thomassen, M. (Mads), Offit, K. (Kenneth), Simard, J. (Jacques), Schmutzler, R.K. (Rita), Hazelett, D. (Dennis), Monteiro, A.N.A. (Alvaro N.), Couch, F.J. (Fergus), Berchuck, A. (Andrew), Chenevix-Trench, G. (Georgia), Goode, E.L. (Ellen), Sellers, T.F., Gayther, S.A. (Simon), Antoniou, A.C. (Antonis), and Pharoah, P.D.P. (Paul)
Abstract: To identify common alleles associated with different histotypes of epithelial ovarian cancer (EOC), we pooled data from multiple genome-wide genotyping projects totaling 25,509 EOC cases and 40,941 controls. We identified nine new susceptibility loci for different EOC histotypes: six for serous EOC histotypes (3q28, 4q32.3, 8q21.11, 10q24.33, 18q11.2 and 22q12.1), two for mucinous EOC (3q22.3 and 9q31.1) and one for endometrioid EOC (5q12.3). We then performed meta-analysis on the results for high-grade serous ovarian cancer with the results from analysis of 31,448 BRCA1 and BRCA2 mutation carriers, including 3,887 mutation carriers with EOC. This identified three additional susceptibility loci at 2q13, 8q24.1 and 12q24.31. Integrated analyses of genes and regulatory biofeatures at each locus predicted candidate susceptibility genes, including OBFC1, a new candidate susceptibility gene for low-grade and borderline serous EOC.
Published: 2017
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5. Expression of L1CAM in curettage or high L1CAM level in preoperative blood samples predicts lymph node metastases and poor outcome in endometrial cancer patients

Author: Tangen, I.L., Kopperud, R.K., Visser, N.C.M., Staff, A.C., Tingulstad, S., Marcickiewicz, J., Amant, F., Bjorge, L., Pijnenborg, J.M.A., Salvesen, H.B., Werner, H.M., Trovik, J., Krakstad, C., Tangen, I.L., Kopperud, R.K., Visser, N.C.M., Staff, A.C., Tingulstad, S., Marcickiewicz, J., Amant, F., Bjorge, L., Pijnenborg, J.M.A., Salvesen, H.B., Werner, H.M., Trovik, J., and Krakstad, C.
Abstract: Item does not contain fulltext, BACKGROUND: Several studies have identified L1 cell adhesion molecule (L1CAM) as a strong prognostic marker in endometrial cancer. To further underline the clinical usefulness of this biomarker, we investigated L1CAM as a predictive marker for lymph node metastases and its prognostic impact in curettage specimens and preoperative plasma samples. In addition, we aimed to validate the prognostic value of L1CAM in hysterectomy specimen. METHODS: Immunohistochemical staining of L1CAM was performed for 795 hysterectomy and 1134 curettage specimen from endometrial cancer patients. The L1CAM level in preoperative blood samples from 372 patients was determined using ELISA. RESULTS: Expression of L1CAM in curettage specimen was significantly correlated to L1CAM level in corresponding hysterectomy specimen (P<0.001). Both in curettage and preoperative plasma samples L1CAM upregulation was significantly associated with features of aggressive disease and poor outcome (P<0.001). The L1CAM was an independent predictor of lymph node metastases, after correction for curettage histology, both in curettage specimen (P=0.002) and plasma samples (P=0.048). In the hysterectomy samples L1CAM was significantly associated with poor outcome (P<0.001). CONCLUSIONS: We demonstrate that preoperative evaluation of L1CAM levels, both in curettage or plasma samples, predicts lymph node metastases and adds valuable information on patient prognosis.
Published: 2017

6. L1CAM expression in endometrial carcinomas: an ENITEC collaboration study

Author: Putten, L.J.M. van der, Visser, N.C.M., Vijver, K. van der, Santacana, M., Bronsert, P., Bulten, J., Hirschfeld, M., Colas, E., Gil-Moreno, A., Garcia, A., Mancebo, G., Alameda, F., Trovik, J., Kopperud, R.K., Huvila, J., Schrauwen, S., Koskas, M., Walker, F., Weinberger, V., Minar, L., Jandakova, E., Snijders, M.P.M.L., Erp, S. van, Matias-Guiu, X., Salvesen, H.B., Amant, F., Massuger, L.F.A.G., Pijnenborg, J.M.A., Putten, L.J.M. van der, Visser, N.C.M., Vijver, K. van der, Santacana, M., Bronsert, P., Bulten, J., Hirschfeld, M., Colas, E., Gil-Moreno, A., Garcia, A., Mancebo, G., Alameda, F., Trovik, J., Kopperud, R.K., Huvila, J., Schrauwen, S., Koskas, M., Walker, F., Weinberger, V., Minar, L., Jandakova, E., Snijders, M.P.M.L., Erp, S. van, Matias-Guiu, X., Salvesen, H.B., Amant, F., Massuger, L.F.A.G., and Pijnenborg, J.M.A.
Abstract: Contains fulltext : 165692.pdf (publisher's version ) (Open Access), BACKGROUND: Identification of aggressive endometrioid endometrial carcinomas (EECs) and non-endometrioid carcinomas (NEECs) is essential to improve outcome. L1 cell adhesion molecule (L1CAM) expression is a strong prognostic marker in stage I EECs, but less is known about L1CAM expression in advanced-stage EECs and NEECs. This study analyses L1CAM expression in a clinically representative cohort of endometrial carcinomas. METHODS: The expression of L1CAM was immunohistochemically determined in 1199 endometrial carcinomas, treated at one of the European Network for Individualized Treatment of Endometrial Cancer (ENITEC) centres. Staining was considered positive when >10% of the tumour cells expressed L1CAM. The association between L1CAM expression and several clincopathological characteristics and disease outcome was calculated. RESULTS: In all, L1CAM was expressed in 10% of the 935 stage I EECs, 18% of the 160 advanced stage EECs, and 75% of the 104 NEECs. The expression of L1CAM was associated with advanced stage, nodal involvement, high tumour grade, non-endometrioid histology, lymphovascular space invasion, and distant recurrences in all cases, and with reduced survival in the EECs, but not in the NEECs. CONCLUSIONS: The expression of L1CAM is a strong predictor of poor outcome in EECs, but not NEECs. It is strongly associated with non-endometrioid histology and distant spread, and could improve the postoperative selection of high-risk endometrial carcinomas. The value of L1CAM expression in the preoperative selection of high-risk endometrial carcinomas should be studied.
Published: 2016

7. Assessing the genetic architecture of epithelial ovarian cancer histological subtypes

Author: Cuellar-Partida, G., Lu, Y., Dixon, S.C., Fasching, P.A., Hein, A., Burghaus, S., Beckmann, M.W., Lambrechts, D., Nieuwenhuysen, E. Van, Vergote, I., Vanderstichele, A., Doherty, J.A., Rossing, M.A., Chang-Claude, J., Rudolph, A., Wang-Gohrke, S., Goodman, M.T., Bogdanova, N., Dork, T., Durst, M., Hillemanns, P., Runnebaum, I.B., Antonenkova, N., Butzow, R., Leminen, A., Nevanlinna, H., Pelttari, L.M., Edwards, R.P., Kelley, J.L., Modugno, F., Moysich, K.B., Ness, R.B., Cannioto, R., Hogdall, E., Hogdall, C., Jensen, A., Giles, G.G., Bruinsma, F., Kjaer, S.K., Hildebrandt, M.A.T., Liang, D., Lu, K.H., Wu, X., Bisogna, M., Dao, F., Levine, D.A., Cramer, D.W, Terry, K.L., Tworoger, S.S., Stampfer, M., Missmer, S., Bjorge, L., Salvesen, H.B., Kopperud, R.K., Bischof, K., Aben, K.K.H., Kiemeney, L.A.L.M., Massuger, L.F.A.G., Brooks-Wilson, A., Olson, S.H., McGuire, V., Rothstein, J.H., Sieh, W., Whittemore, A.S., Cook, L.S., Le, N.D., Gilks, C. Blake, Gronwald, J., Jakubowska, A., Lubinski, J., Kluz, T., Song, H., Tyrer, J.P., Wentzensen, N., Brinton, L., Trabert, B., Lissowska, J., McLaughlin, J.R., Narod, S.A., Phelan, C., Anton-Culver, H., Ziogas, A., Eccles, D., Campbell, I., Gayther, S.A., Gentry-Maharaj, A., Menon, U., Ramus, S.J., Wu, A.H., Dansonka-Mieszkowska, A., Kupryjanczyk, J., Timorek, A., Szafron, L., Cunningham, J.M., Fridley, B.L., Winham, S.J., Bandera, E.V., Poole, E.M., Morgan, T.K., Goode, E.L., Cuellar-Partida, G., Lu, Y., Dixon, S.C., Fasching, P.A., Hein, A., Burghaus, S., Beckmann, M.W., Lambrechts, D., Nieuwenhuysen, E. Van, Vergote, I., Vanderstichele, A., Doherty, J.A., Rossing, M.A., Chang-Claude, J., Rudolph, A., Wang-Gohrke, S., Goodman, M.T., Bogdanova, N., Dork, T., Durst, M., Hillemanns, P., Runnebaum, I.B., Antonenkova, N., Butzow, R., Leminen, A., Nevanlinna, H., Pelttari, L.M., Edwards, R.P., Kelley, J.L., Modugno, F., Moysich, K.B., Ness, R.B., Cannioto, R., Hogdall, E., Hogdall, C., Jensen, A., Giles, G.G., Bruinsma, F., Kjaer, S.K., Hildebrandt, M.A.T., Liang, D., Lu, K.H., Wu, X., Bisogna, M., Dao, F., Levine, D.A., Cramer, D.W, Terry, K.L., Tworoger, S.S., Stampfer, M., Missmer, S., Bjorge, L., Salvesen, H.B., Kopperud, R.K., Bischof, K., Aben, K.K.H., Kiemeney, L.A.L.M., Massuger, L.F.A.G., Brooks-Wilson, A., Olson, S.H., McGuire, V., Rothstein, J.H., Sieh, W., Whittemore, A.S., Cook, L.S., Le, N.D., Gilks, C. Blake, Gronwald, J., Jakubowska, A., Lubinski, J., Kluz, T., Song, H., Tyrer, J.P., Wentzensen, N., Brinton, L., Trabert, B., Lissowska, J., McLaughlin, J.R., Narod, S.A., Phelan, C., Anton-Culver, H., Ziogas, A., Eccles, D., Campbell, I., Gayther, S.A., Gentry-Maharaj, A., Menon, U., Ramus, S.J., Wu, A.H., Dansonka-Mieszkowska, A., Kupryjanczyk, J., Timorek, A., Szafron, L., Cunningham, J.M., Fridley, B.L., Winham, S.J., Bandera, E.V., Poole, E.M., Morgan, T.K., and Goode, E.L.
Abstract: Contains fulltext : 171782.pdf (publisher's version ) (Closed access), Epithelial ovarian cancer (EOC) is one of the deadliest common cancers. The five most common types of disease are high-grade and low-grade serous, endometrioid, mucinous and clear cell carcinoma. Each of these subtypes present distinct molecular pathogeneses and sensitivities to treatments. Recent studies show that certain genetic variants confer susceptibility to all subtypes while other variants are subtype-specific. Here, we perform an extensive analysis of the genetic architecture of EOC subtypes. To this end, we used data of 10,014 invasive EOC patients and 21,233 controls from the Ovarian Cancer Association Consortium genotyped in the iCOGS array (211,155 SNPs). We estimate the array heritability (attributable to variants tagged on arrays) of each subtype and their genetic correlations. We also look for genetic overlaps with factors such as obesity, smoking behaviors, diabetes, age at menarche and height. We estimated the array heritabilities of high-grade serous disease ([Formula: see text] = 8.8 +/- 1.1 %), endometrioid ([Formula: see text] = 3.2 +/- 1.6 %), clear cell ([Formula: see text] = 6.7 +/- 3.3 %) and all EOC ([Formula: see text] = 5.6 +/- 0.6 %). Known associated loci contributed approximately 40 % of the total array heritability for each subtype. The contribution of each chromosome to the total heritability was not proportional to chromosome size. Through bivariate and cross-trait LD score regression, we found evidence of shared genetic backgrounds between the three high-grade subtypes: serous, endometrioid and undifferentiated. Finally, we found significant genetic correlations of all EOC with diabetes and obesity using a polygenic prediction approach.
Published: 2016

8. Adult body mass index and risk of ovarian cancer by subtype: a Mendelian randomization study

Author: Dixon, S.C., Nagle, C.M., Thrift, A.P., Pharoah, P.D., Pearce, C.L., Zheng, W., Painter, J.N., Chenevix-Trench, G., Fasching, P.A., Beckmann, M.W., Lambrechts, D., Vergote, I., Lambrechts, S., Nieuwenhuysen, E. Van, Rossing, M.A., Doherty, J.A., Wicklund, K.G., Chang-Claude, J., Rudolph, A., Moysich, K.B., Odunsi, K., Goodman, M.T., Wilkens, L.R., Thompson, P.J., Shvetsov, Y.B., Dork, T., Park-Simon, T.W., Hillemanns, P., Bogdanova, N., Butzow, R., Nevanlinna, H., Pelttari, L.M., Leminen, A., Modugno, F., Ness, R.B., Edwards, R.P., Kelley, J.L., Heitz, F., Karlan, B.Y., Kjaer, S.K., Hogdall, E., Jensen, A., Goode, E.L., Fridley, B.L., Cunningham, J.M., Winham, S.J., Giles, G.G., Bruinsma, F., Milne, R.L., Southey, M.C., Hildebrandt, M.A.T., Wu, X., Lu, K.H., Liang, D., Levine, D.A., Bisogna, M., Schildkraut, J.M., Berchuck, A., Cramer, D.W, Terry, K.L., Bandera, E.V., Olson, S.H., Salvesen, H.B., Thomsen, L.C., Kopperud, R.K., Bjorge, L., Kiemeney, L.A.L.M., Massuger, L.F.A.G., Pejovic, T., Cook, L.S., Le, N.D., Swenerton, K.D., Brooks-Wilson, A., Kelemen, L.E., Lubinski, J., Huzarski, T., Gronwald, J., Menkiszak, J., Wentzensen, N., Brinton, L., Yang, H., Lissowska, J., Hogdall, C.K., Lundvall, L., Song, H., Tyrer, J.P., Campbell, I., Eccles, D., Paul, J., Glasspool, R., Siddiqui, N., Whittemore, A.S., Sieh, W., McGuire, V., Rothstein, J.H., Narod, S.A., Phelan, C., Risch, H.A., McLaughlin, J.R., Anton-Culver, H., et al., Dixon, S.C., Nagle, C.M., Thrift, A.P., Pharoah, P.D., Pearce, C.L., Zheng, W., Painter, J.N., Chenevix-Trench, G., Fasching, P.A., Beckmann, M.W., Lambrechts, D., Vergote, I., Lambrechts, S., Nieuwenhuysen, E. Van, Rossing, M.A., Doherty, J.A., Wicklund, K.G., Chang-Claude, J., Rudolph, A., Moysich, K.B., Odunsi, K., Goodman, M.T., Wilkens, L.R., Thompson, P.J., Shvetsov, Y.B., Dork, T., Park-Simon, T.W., Hillemanns, P., Bogdanova, N., Butzow, R., Nevanlinna, H., Pelttari, L.M., Leminen, A., Modugno, F., Ness, R.B., Edwards, R.P., Kelley, J.L., Heitz, F., Karlan, B.Y., Kjaer, S.K., Hogdall, E., Jensen, A., Goode, E.L., Fridley, B.L., Cunningham, J.M., Winham, S.J., Giles, G.G., Bruinsma, F., Milne, R.L., Southey, M.C., Hildebrandt, M.A.T., Wu, X., Lu, K.H., Liang, D., Levine, D.A., Bisogna, M., Schildkraut, J.M., Berchuck, A., Cramer, D.W, Terry, K.L., Bandera, E.V., Olson, S.H., Salvesen, H.B., Thomsen, L.C., Kopperud, R.K., Bjorge, L., Kiemeney, L.A.L.M., Massuger, L.F.A.G., Pejovic, T., Cook, L.S., Le, N.D., Swenerton, K.D., Brooks-Wilson, A., Kelemen, L.E., Lubinski, J., Huzarski, T., Gronwald, J., Menkiszak, J., Wentzensen, N., Brinton, L., Yang, H., Lissowska, J., Hogdall, C.K., Lundvall, L., Song, H., Tyrer, J.P., Campbell, I., Eccles, D., Paul, J., Glasspool, R., Siddiqui, N., Whittemore, A.S., Sieh, W., McGuire, V., Rothstein, J.H., Narod, S.A., Phelan, C., Risch, H.A., McLaughlin, J.R., and Anton-Culver, H., et al.
Abstract: Contains fulltext : 170949.pdf (publisher's version ) (Closed access), BACKGROUND: Observational studies have reported a positive association between body mass index (BMI) and ovarian cancer risk. However, questions remain as to whether this represents a causal effect, or holds for all histological subtypes. The lack of association observed for serous cancers may, for instance, be due to disease-associated weight loss. Mendelian randomization (MR) uses genetic markers as proxies for risk factors to overcome limitations of observational studies. We used MR to elucidate the relationship between BMI and ovarian cancer, hypothesizing that genetically predicted BMI would be associated with increased risk of non-high grade serous ovarian cancers (non-HGSC) but not HGSC. METHODS: We pooled data from 39 studies (14 047 cases, 23 003 controls) in the Ovarian Cancer Association Consortium. We constructed a weighted genetic risk score (GRS, partial F-statistic = 172), summing alleles at 87 single nucleotide polymorphisms previously associated with BMI, weighting by their published strength of association with BMI. Applying two-stage predictor-substitution MR, we used logistic regression to estimate study-specific odds ratios (OR) and 95% confidence intervals (CI) for the association between genetically predicted BMI and risk, and pooled these using random-effects meta-analysis. RESULTS: Higher genetically predicted BMI was associated with increased risk of non-HGSC (pooled OR = 1.29, 95% CI 1.03-1.61 per 5 units BMI) but not HGSC (pooled OR = 1.06, 95% CI 0.88-1.27). Secondary analyses stratified by behaviour/subtype suggested that, consistent with observational data, the association was strongest for low-grade/borderline serous cancers (OR = 1.93, 95% CI 1.33-2.81). CONCLUSIONS: Our data suggest that higher BMI increases risk of non-HGSC, but not the more common and aggressive HGSC subtype, confirming the observational evidence.
Published: 2016

9. Association of vitamin D levels and risk of ovarian cancer: a Mendelian randomization study

Author: Ong, J.S., Cuellar-Partida, G., Lu, Y., Fasching, P.A., Hein, A., Burghaus, S., Beckmann, M.W., Lambrechts, D., Nieuwenhuysen, E. Van, Vergote, I., Vanderstichele, A., Doherty, J., Rossing, M. Anne, Chang-Claude, J., Eilber, U., Rudolph, A., Wang-Gohrke, S., Goodman, M.T., Bogdanova, N., Dork, T., Durst, M., Hillemanns, P., Runnebaum, I.B., Antonenkova, N., Butzow, R., Leminen, A., Nevanlinna, H., Pelttari, L.M., Edwards, R.P., Kelley, J.L., Modugno, F., Moysich, K.B., Ness, R.B., Cannioto, R., Hogdall, E., Hogdall, C.K., Jensen, A., Giles, G.G., Bruinsma, F., Kjaer, S.K., Hildebrandt, M.A.T., Liang, D., Lu, K.H., Wu, X., Bisogna, M., Dao, F., Levine, D.A., Cramer, D.W, Terry, K.L., Tworoger, S.S., Stampfer, M., Missmer, S., Bjorge, L., Salvesen, H.B., Kopperud, R.K., Bischof, K., Aben, K.K.H., Kiemeney, L.A.L.M., Massuger, L.F.A.G., Brooks-Wilson, A., Olson, S.H., McGuire, V., Rothstein, J.H., Sieh, W., Whittemore, A.S., Cook, L.S., Le, N.D., Gilks, C.B., Gronwald, J., Jakubowska, A., Lubinski, J., Kluz, T., Song, H., Tyrer, J.P., Wentzensen, N., Brinton, L., Trabert, B., Lissowska, J., McLaughlin, J.R., Narod, S.A., Phelan, C., Anton-Culver, H., Ziogas, A., Eccles, D., Campbell, I., Gayther, S.A., Gentry-Maharaj, A., Menon, U., Ramus, S.J., Wu, A.H., Dansonka-Mieszkowska, A., Kupryjanczyk, J., Timorek, A., Szafron, L., Cunningham, J.M., Fridley, B.L., Winham, S.J., Bandera, E.V., Poole, E.M., Morgan, T.K., Ong, J.S., Cuellar-Partida, G., Lu, Y., Fasching, P.A., Hein, A., Burghaus, S., Beckmann, M.W., Lambrechts, D., Nieuwenhuysen, E. Van, Vergote, I., Vanderstichele, A., Doherty, J., Rossing, M. Anne, Chang-Claude, J., Eilber, U., Rudolph, A., Wang-Gohrke, S., Goodman, M.T., Bogdanova, N., Dork, T., Durst, M., Hillemanns, P., Runnebaum, I.B., Antonenkova, N., Butzow, R., Leminen, A., Nevanlinna, H., Pelttari, L.M., Edwards, R.P., Kelley, J.L., Modugno, F., Moysich, K.B., Ness, R.B., Cannioto, R., Hogdall, E., Hogdall, C.K., Jensen, A., Giles, G.G., Bruinsma, F., Kjaer, S.K., Hildebrandt, M.A.T., Liang, D., Lu, K.H., Wu, X., Bisogna, M., Dao, F., Levine, D.A., Cramer, D.W, Terry, K.L., Tworoger, S.S., Stampfer, M., Missmer, S., Bjorge, L., Salvesen, H.B., Kopperud, R.K., Bischof, K., Aben, K.K.H., Kiemeney, L.A.L.M., Massuger, L.F.A.G., Brooks-Wilson, A., Olson, S.H., McGuire, V., Rothstein, J.H., Sieh, W., Whittemore, A.S., Cook, L.S., Le, N.D., Gilks, C.B., Gronwald, J., Jakubowska, A., Lubinski, J., Kluz, T., Song, H., Tyrer, J.P., Wentzensen, N., Brinton, L., Trabert, B., Lissowska, J., McLaughlin, J.R., Narod, S.A., Phelan, C., Anton-Culver, H., Ziogas, A., Eccles, D., Campbell, I., Gayther, S.A., Gentry-Maharaj, A., Menon, U., Ramus, S.J., Wu, A.H., Dansonka-Mieszkowska, A., Kupryjanczyk, J., Timorek, A., Szafron, L., Cunningham, J.M., Fridley, B.L., Winham, S.J., Bandera, E.V., Poole, E.M., and Morgan, T.K.
Abstract: Contains fulltext : 171904.pdf (publisher's version ) (Closed access), BACKGROUND: In vitro and observational epidemiological studies suggest that vitamin D may play a role in cancer prevention. However, the relationship between vitamin D and ovarian cancer is uncertain, with observational studies generating conflicting findings. A potential limitation of observational studies is inadequate control of confounding. To overcome this problem, we used Mendelian randomization (MR) to evaluate the association between single nucleotide polymorphisms (SNPs) associated with circulating 25-hydroxyvitamin D [25(OH)D] concentration and risk of ovarian cancer. METHODS: We employed SNPs with well-established associations with 25(OH)D concentration as instrumental variables for MR: rs7944926 (DHCR7), rs12794714 (CYP2R1) and rs2282679 (GC). We included 31 719 women of European ancestry (10 065 cases, 21 654 controls) from the Ovarian Cancer Association Consortium, who were genotyped using customized Illumina Infinium iSelect (iCOGS) arrays. A two-sample (summary data) MR approach was used and analyses were performed separately for all ovarian cancer (10 065 cases) and for high-grade serous ovarian cancer (4121 cases). RESULTS: The odds ratio for epithelial ovarian cancer risk (10 065 cases) estimated by combining the individual SNP associations using inverse variance weighting was 1.27 (95% confidence interval: 1.06 to 1.51) per 20 nmol/L decrease in 25(OH)D concentration. The estimated odds ratio for high-grade serous epithelial ovarian cancer (4121 cases) was 1.54 (1.19, 2.01). CONCLUSIONS: Genetically lowered 25-hydroxyvitamin D concentrations were associated with higher ovarian cancer susceptibility in Europeans. These findings suggest that increasing plasma vitamin D levels may reduce risk of ovarian cancer.
Published: 2016

10. L1CAM expression in endometrial carcinomas: an ENITEC collaboration study

Author: Putten, L.J.M. van der, Visser, N.C.M., Vijver, K. van der, Santacana, M., Bronsert, P., Bulten, J., Hirschfeld, M., Colas, E., Gil-Moreno, A., Garcia, A., Mancebo, G., Alameda, F., Trovik, J., Kopperud, R.K., Huvila, J., Schrauwen, S., Koskas, M., Walker, F., Weinberger, V., Minar, L., Jandakova, E., Snijders, M.P.M.L., Erp, S. van, Matias-Guiu, X., Salvesen, H.B., Amant, F., Massuger, L.F.A.G., Pijnenborg, J.M.A., Putten, L.J.M. van der, Visser, N.C.M., Vijver, K. van der, Santacana, M., Bronsert, P., Bulten, J., Hirschfeld, M., Colas, E., Gil-Moreno, A., Garcia, A., Mancebo, G., Alameda, F., Trovik, J., Kopperud, R.K., Huvila, J., Schrauwen, S., Koskas, M., Walker, F., Weinberger, V., Minar, L., Jandakova, E., Snijders, M.P.M.L., Erp, S. van, Matias-Guiu, X., Salvesen, H.B., Amant, F., Massuger, L.F.A.G., and Pijnenborg, J.M.A.
Abstract: Contains fulltext : 165692.pdf (publisher's version ) (Open Access), BACKGROUND: Identification of aggressive endometrioid endometrial carcinomas (EECs) and non-endometrioid carcinomas (NEECs) is essential to improve outcome. L1 cell adhesion molecule (L1CAM) expression is a strong prognostic marker in stage I EECs, but less is known about L1CAM expression in advanced-stage EECs and NEECs. This study analyses L1CAM expression in a clinically representative cohort of endometrial carcinomas. METHODS: The expression of L1CAM was immunohistochemically determined in 1199 endometrial carcinomas, treated at one of the European Network for Individualized Treatment of Endometrial Cancer (ENITEC) centres. Staining was considered positive when >10% of the tumour cells expressed L1CAM. The association between L1CAM expression and several clincopathological characteristics and disease outcome was calculated. RESULTS: In all, L1CAM was expressed in 10% of the 935 stage I EECs, 18% of the 160 advanced stage EECs, and 75% of the 104 NEECs. The expression of L1CAM was associated with advanced stage, nodal involvement, high tumour grade, non-endometrioid histology, lymphovascular space invasion, and distant recurrences in all cases, and with reduced survival in the EECs, but not in the NEECs. CONCLUSIONS: The expression of L1CAM is a strong predictor of poor outcome in EECs, but not NEECs. It is strongly associated with non-endometrioid histology and distant spread, and could improve the postoperative selection of high-risk endometrial carcinomas. The value of L1CAM expression in the preoperative selection of high-risk endometrial carcinomas should be studied.
Published: 2016

11. Assessing the genetic architecture of epithelial ovarian cancer histological subtypes

Author: Cuellar-Partida, G., Lu, Y., Dixon, S.C., Fasching, P.A., Hein, A., Burghaus, S., Beckmann, M.W., Lambrechts, D., Nieuwenhuysen, E. Van, Vergote, I., Vanderstichele, A., Doherty, J.A., Rossing, M.A., Chang-Claude, J., Rudolph, A., Wang-Gohrke, S., Goodman, M.T., Bogdanova, N., Dork, T., Durst, M., Hillemanns, P., Runnebaum, I.B., Antonenkova, N., Butzow, R., Leminen, A., Nevanlinna, H., Pelttari, L.M., Edwards, R.P., Kelley, J.L., Modugno, F., Moysich, K.B., Ness, R.B., Cannioto, R., Hogdall, E., Hogdall, C., Jensen, A., Giles, G.G., Bruinsma, F., Kjaer, S.K., Hildebrandt, M.A.T., Liang, D., Lu, K.H., Wu, X., Bisogna, M., Dao, F., Levine, D.A., Cramer, D.W, Terry, K.L., Tworoger, S.S., Stampfer, M., Missmer, S., Bjorge, L., Salvesen, H.B., Kopperud, R.K., Bischof, K., Aben, K.K.H., Kiemeney, L.A.L.M., Massuger, L.F.A.G., Brooks-Wilson, A., Olson, S.H., McGuire, V., Rothstein, J.H., Sieh, W., Whittemore, A.S., Cook, L.S., Le, N.D., Gilks, C. Blake, Gronwald, J., Jakubowska, A., Lubinski, J., Kluz, T., Song, H., Tyrer, J.P., Wentzensen, N., Brinton, L., Trabert, B., Lissowska, J., McLaughlin, J.R., Narod, S.A., Phelan, C., Anton-Culver, H., Ziogas, A., Eccles, D., Campbell, I., Gayther, S.A., Gentry-Maharaj, A., Menon, U., Ramus, S.J., Wu, A.H., Dansonka-Mieszkowska, A., Kupryjanczyk, J., Timorek, A., Szafron, L., Cunningham, J.M., Fridley, B.L., Winham, S.J., Bandera, E.V., Poole, E.M., Morgan, T.K., Goode, E.L., Cuellar-Partida, G., Lu, Y., Dixon, S.C., Fasching, P.A., Hein, A., Burghaus, S., Beckmann, M.W., Lambrechts, D., Nieuwenhuysen, E. Van, Vergote, I., Vanderstichele, A., Doherty, J.A., Rossing, M.A., Chang-Claude, J., Rudolph, A., Wang-Gohrke, S., Goodman, M.T., Bogdanova, N., Dork, T., Durst, M., Hillemanns, P., Runnebaum, I.B., Antonenkova, N., Butzow, R., Leminen, A., Nevanlinna, H., Pelttari, L.M., Edwards, R.P., Kelley, J.L., Modugno, F., Moysich, K.B., Ness, R.B., Cannioto, R., Hogdall, E., Hogdall, C., Jensen, A., Giles, G.G., Bruinsma, F., Kjaer, S.K., Hildebrandt, M.A.T., Liang, D., Lu, K.H., Wu, X., Bisogna, M., Dao, F., Levine, D.A., Cramer, D.W, Terry, K.L., Tworoger, S.S., Stampfer, M., Missmer, S., Bjorge, L., Salvesen, H.B., Kopperud, R.K., Bischof, K., Aben, K.K.H., Kiemeney, L.A.L.M., Massuger, L.F.A.G., Brooks-Wilson, A., Olson, S.H., McGuire, V., Rothstein, J.H., Sieh, W., Whittemore, A.S., Cook, L.S., Le, N.D., Gilks, C. Blake, Gronwald, J., Jakubowska, A., Lubinski, J., Kluz, T., Song, H., Tyrer, J.P., Wentzensen, N., Brinton, L., Trabert, B., Lissowska, J., McLaughlin, J.R., Narod, S.A., Phelan, C., Anton-Culver, H., Ziogas, A., Eccles, D., Campbell, I., Gayther, S.A., Gentry-Maharaj, A., Menon, U., Ramus, S.J., Wu, A.H., Dansonka-Mieszkowska, A., Kupryjanczyk, J., Timorek, A., Szafron, L., Cunningham, J.M., Fridley, B.L., Winham, S.J., Bandera, E.V., Poole, E.M., Morgan, T.K., and Goode, E.L.
Abstract: Contains fulltext : 171782.pdf (publisher's version ) (Closed access), Epithelial ovarian cancer (EOC) is one of the deadliest common cancers. The five most common types of disease are high-grade and low-grade serous, endometrioid, mucinous and clear cell carcinoma. Each of these subtypes present distinct molecular pathogeneses and sensitivities to treatments. Recent studies show that certain genetic variants confer susceptibility to all subtypes while other variants are subtype-specific. Here, we perform an extensive analysis of the genetic architecture of EOC subtypes. To this end, we used data of 10,014 invasive EOC patients and 21,233 controls from the Ovarian Cancer Association Consortium genotyped in the iCOGS array (211,155 SNPs). We estimate the array heritability (attributable to variants tagged on arrays) of each subtype and their genetic correlations. We also look for genetic overlaps with factors such as obesity, smoking behaviors, diabetes, age at menarche and height. We estimated the array heritabilities of high-grade serous disease ([Formula: see text] = 8.8 +/- 1.1 %), endometrioid ([Formula: see text] = 3.2 +/- 1.6 %), clear cell ([Formula: see text] = 6.7 +/- 3.3 %) and all EOC ([Formula: see text] = 5.6 +/- 0.6 %). Known associated loci contributed approximately 40 % of the total array heritability for each subtype. The contribution of each chromosome to the total heritability was not proportional to chromosome size. Through bivariate and cross-trait LD score regression, we found evidence of shared genetic backgrounds between the three high-grade subtypes: serous, endometrioid and undifferentiated. Finally, we found significant genetic correlations of all EOC with diabetes and obesity using a polygenic prediction approach.
Published: 2016

12. Adult body mass index and risk of ovarian cancer by subtype: a Mendelian randomization study

Author: Dixon, S.C., Nagle, C.M., Thrift, A.P., Pharoah, P.D., Pearce, C.L., Zheng, W., Painter, J.N., Chenevix-Trench, G., Fasching, P.A., Beckmann, M.W., Lambrechts, D., Vergote, I., Lambrechts, S., Nieuwenhuysen, E. Van, Rossing, M.A., Doherty, J.A., Wicklund, K.G., Chang-Claude, J., Rudolph, A., Moysich, K.B., Odunsi, K., Goodman, M.T., Wilkens, L.R., Thompson, P.J., Shvetsov, Y.B., Dork, T., Park-Simon, T.W., Hillemanns, P., Bogdanova, N., Butzow, R., Nevanlinna, H., Pelttari, L.M., Leminen, A., Modugno, F., Ness, R.B., Edwards, R.P., Kelley, J.L., Heitz, F., Karlan, B.Y., Kjaer, S.K., Hogdall, E., Jensen, A., Goode, E.L., Fridley, B.L., Cunningham, J.M., Winham, S.J., Giles, G.G., Bruinsma, F., Milne, R.L., Southey, M.C., Hildebrandt, M.A.T., Wu, X., Lu, K.H., Liang, D., Levine, D.A., Bisogna, M., Schildkraut, J.M., Berchuck, A., Cramer, D.W, Terry, K.L., Bandera, E.V., Olson, S.H., Salvesen, H.B., Thomsen, L.C., Kopperud, R.K., Bjorge, L., Kiemeney, L.A.L.M., Massuger, L.F.A.G., Pejovic, T., Cook, L.S., Le, N.D., Swenerton, K.D., Brooks-Wilson, A., Kelemen, L.E., Lubinski, J., Huzarski, T., Gronwald, J., Menkiszak, J., Wentzensen, N., Brinton, L., Yang, H., Lissowska, J., Hogdall, C.K., Lundvall, L., Song, H., Tyrer, J.P., Campbell, I., Eccles, D., Paul, J., Glasspool, R., Siddiqui, N., Whittemore, A.S., Sieh, W., McGuire, V., Rothstein, J.H., Narod, S.A., Phelan, C., Risch, H.A., McLaughlin, J.R., Anton-Culver, H., et al., Dixon, S.C., Nagle, C.M., Thrift, A.P., Pharoah, P.D., Pearce, C.L., Zheng, W., Painter, J.N., Chenevix-Trench, G., Fasching, P.A., Beckmann, M.W., Lambrechts, D., Vergote, I., Lambrechts, S., Nieuwenhuysen, E. Van, Rossing, M.A., Doherty, J.A., Wicklund, K.G., Chang-Claude, J., Rudolph, A., Moysich, K.B., Odunsi, K., Goodman, M.T., Wilkens, L.R., Thompson, P.J., Shvetsov, Y.B., Dork, T., Park-Simon, T.W., Hillemanns, P., Bogdanova, N., Butzow, R., Nevanlinna, H., Pelttari, L.M., Leminen, A., Modugno, F., Ness, R.B., Edwards, R.P., Kelley, J.L., Heitz, F., Karlan, B.Y., Kjaer, S.K., Hogdall, E., Jensen, A., Goode, E.L., Fridley, B.L., Cunningham, J.M., Winham, S.J., Giles, G.G., Bruinsma, F., Milne, R.L., Southey, M.C., Hildebrandt, M.A.T., Wu, X., Lu, K.H., Liang, D., Levine, D.A., Bisogna, M., Schildkraut, J.M., Berchuck, A., Cramer, D.W, Terry, K.L., Bandera, E.V., Olson, S.H., Salvesen, H.B., Thomsen, L.C., Kopperud, R.K., Bjorge, L., Kiemeney, L.A.L.M., Massuger, L.F.A.G., Pejovic, T., Cook, L.S., Le, N.D., Swenerton, K.D., Brooks-Wilson, A., Kelemen, L.E., Lubinski, J., Huzarski, T., Gronwald, J., Menkiszak, J., Wentzensen, N., Brinton, L., Yang, H., Lissowska, J., Hogdall, C.K., Lundvall, L., Song, H., Tyrer, J.P., Campbell, I., Eccles, D., Paul, J., Glasspool, R., Siddiqui, N., Whittemore, A.S., Sieh, W., McGuire, V., Rothstein, J.H., Narod, S.A., Phelan, C., Risch, H.A., McLaughlin, J.R., and Anton-Culver, H., et al.
Abstract: Contains fulltext : 170949.pdf (publisher's version ) (Closed access), BACKGROUND: Observational studies have reported a positive association between body mass index (BMI) and ovarian cancer risk. However, questions remain as to whether this represents a causal effect, or holds for all histological subtypes. The lack of association observed for serous cancers may, for instance, be due to disease-associated weight loss. Mendelian randomization (MR) uses genetic markers as proxies for risk factors to overcome limitations of observational studies. We used MR to elucidate the relationship between BMI and ovarian cancer, hypothesizing that genetically predicted BMI would be associated with increased risk of non-high grade serous ovarian cancers (non-HGSC) but not HGSC. METHODS: We pooled data from 39 studies (14 047 cases, 23 003 controls) in the Ovarian Cancer Association Consortium. We constructed a weighted genetic risk score (GRS, partial F-statistic = 172), summing alleles at 87 single nucleotide polymorphisms previously associated with BMI, weighting by their published strength of association with BMI. Applying two-stage predictor-substitution MR, we used logistic regression to estimate study-specific odds ratios (OR) and 95% confidence intervals (CI) for the association between genetically predicted BMI and risk, and pooled these using random-effects meta-analysis. RESULTS: Higher genetically predicted BMI was associated with increased risk of non-HGSC (pooled OR = 1.29, 95% CI 1.03-1.61 per 5 units BMI) but not HGSC (pooled OR = 1.06, 95% CI 0.88-1.27). Secondary analyses stratified by behaviour/subtype suggested that, consistent with observational data, the association was strongest for low-grade/borderline serous cancers (OR = 1.93, 95% CI 1.33-2.81). CONCLUSIONS: Our data suggest that higher BMI increases risk of non-HGSC, but not the more common and aggressive HGSC subtype, confirming the observational evidence.
Published: 2016

13. Association of vitamin D levels and risk of ovarian cancer: a Mendelian randomization study

Author: Ong, J.S., Cuellar-Partida, G., Lu, Y., Fasching, P.A., Hein, A., Burghaus, S., Beckmann, M.W., Lambrechts, D., Nieuwenhuysen, E. Van, Vergote, I., Vanderstichele, A., Doherty, J., Rossing, M. Anne, Chang-Claude, J., Eilber, U., Rudolph, A., Wang-Gohrke, S., Goodman, M.T., Bogdanova, N., Dork, T., Durst, M., Hillemanns, P., Runnebaum, I.B., Antonenkova, N., Butzow, R., Leminen, A., Nevanlinna, H., Pelttari, L.M., Edwards, R.P., Kelley, J.L., Modugno, F., Moysich, K.B., Ness, R.B., Cannioto, R., Hogdall, E., Hogdall, C.K., Jensen, A., Giles, G.G., Bruinsma, F., Kjaer, S.K., Hildebrandt, M.A.T., Liang, D., Lu, K.H., Wu, X., Bisogna, M., Dao, F., Levine, D.A., Cramer, D.W, Terry, K.L., Tworoger, S.S., Stampfer, M., Missmer, S., Bjorge, L., Salvesen, H.B., Kopperud, R.K., Bischof, K., Aben, K.K.H., Kiemeney, L.A.L.M., Massuger, L.F.A.G., Brooks-Wilson, A., Olson, S.H., McGuire, V., Rothstein, J.H., Sieh, W., Whittemore, A.S., Cook, L.S., Le, N.D., Gilks, C.B., Gronwald, J., Jakubowska, A., Lubinski, J., Kluz, T., Song, H., Tyrer, J.P., Wentzensen, N., Brinton, L., Trabert, B., Lissowska, J., McLaughlin, J.R., Narod, S.A., Phelan, C., Anton-Culver, H., Ziogas, A., Eccles, D., Campbell, I., Gayther, S.A., Gentry-Maharaj, A., Menon, U., Ramus, S.J., Wu, A.H., Dansonka-Mieszkowska, A., Kupryjanczyk, J., Timorek, A., Szafron, L., Cunningham, J.M., Fridley, B.L., Winham, S.J., Bandera, E.V., Poole, E.M., Morgan, T.K., Ong, J.S., Cuellar-Partida, G., Lu, Y., Fasching, P.A., Hein, A., Burghaus, S., Beckmann, M.W., Lambrechts, D., Nieuwenhuysen, E. Van, Vergote, I., Vanderstichele, A., Doherty, J., Rossing, M. Anne, Chang-Claude, J., Eilber, U., Rudolph, A., Wang-Gohrke, S., Goodman, M.T., Bogdanova, N., Dork, T., Durst, M., Hillemanns, P., Runnebaum, I.B., Antonenkova, N., Butzow, R., Leminen, A., Nevanlinna, H., Pelttari, L.M., Edwards, R.P., Kelley, J.L., Modugno, F., Moysich, K.B., Ness, R.B., Cannioto, R., Hogdall, E., Hogdall, C.K., Jensen, A., Giles, G.G., Bruinsma, F., Kjaer, S.K., Hildebrandt, M.A.T., Liang, D., Lu, K.H., Wu, X., Bisogna, M., Dao, F., Levine, D.A., Cramer, D.W, Terry, K.L., Tworoger, S.S., Stampfer, M., Missmer, S., Bjorge, L., Salvesen, H.B., Kopperud, R.K., Bischof, K., Aben, K.K.H., Kiemeney, L.A.L.M., Massuger, L.F.A.G., Brooks-Wilson, A., Olson, S.H., McGuire, V., Rothstein, J.H., Sieh, W., Whittemore, A.S., Cook, L.S., Le, N.D., Gilks, C.B., Gronwald, J., Jakubowska, A., Lubinski, J., Kluz, T., Song, H., Tyrer, J.P., Wentzensen, N., Brinton, L., Trabert, B., Lissowska, J., McLaughlin, J.R., Narod, S.A., Phelan, C., Anton-Culver, H., Ziogas, A., Eccles, D., Campbell, I., Gayther, S.A., Gentry-Maharaj, A., Menon, U., Ramus, S.J., Wu, A.H., Dansonka-Mieszkowska, A., Kupryjanczyk, J., Timorek, A., Szafron, L., Cunningham, J.M., Fridley, B.L., Winham, S.J., Bandera, E.V., Poole, E.M., and Morgan, T.K.
Abstract: Contains fulltext : 171904.pdf (publisher's version ) (Closed access), BACKGROUND: In vitro and observational epidemiological studies suggest that vitamin D may play a role in cancer prevention. However, the relationship between vitamin D and ovarian cancer is uncertain, with observational studies generating conflicting findings. A potential limitation of observational studies is inadequate control of confounding. To overcome this problem, we used Mendelian randomization (MR) to evaluate the association between single nucleotide polymorphisms (SNPs) associated with circulating 25-hydroxyvitamin D [25(OH)D] concentration and risk of ovarian cancer. METHODS: We employed SNPs with well-established associations with 25(OH)D concentration as instrumental variables for MR: rs7944926 (DHCR7), rs12794714 (CYP2R1) and rs2282679 (GC). We included 31 719 women of European ancestry (10 065 cases, 21 654 controls) from the Ovarian Cancer Association Consortium, who were genotyped using customized Illumina Infinium iSelect (iCOGS) arrays. A two-sample (summary data) MR approach was used and analyses were performed separately for all ovarian cancer (10 065 cases) and for high-grade serous ovarian cancer (4121 cases). RESULTS: The odds ratio for epithelial ovarian cancer risk (10 065 cases) estimated by combining the individual SNP associations using inverse variance weighting was 1.27 (95% confidence interval: 1.06 to 1.51) per 20 nmol/L decrease in 25(OH)D concentration. The estimated odds ratio for high-grade serous epithelial ovarian cancer (4121 cases) was 1.54 (1.19, 2.01). CONCLUSIONS: Genetically lowered 25-hydroxyvitamin D concentrations were associated with higher ovarian cancer susceptibility in Europeans. These findings suggest that increasing plasma vitamin D levels may reduce risk of ovarian cancer.
Published: 2016

14. L1CAM expression in endometrial carcinomas: an ENITEC collaboration study

Author: Putten, L.J.M. van der, Visser, N.C.M., Vijver, K. van der, Santacana, M., Bronsert, P., Bulten, J., Hirschfeld, M., Colas, E., Gil-Moreno, A., Garcia, A., Mancebo, G., Alameda, F., Trovik, J., Kopperud, R.K., Huvila, J., Schrauwen, S., Koskas, M., Walker, F., Weinberger, V., Minar, L., Jandakova, E., Snijders, M.P.M.L., Erp, S. van, Matias-Guiu, X., Salvesen, H.B., Amant, F., Massuger, L.F.A.G., Pijnenborg, J.M.A., Putten, L.J.M. van der, Visser, N.C.M., Vijver, K. van der, Santacana, M., Bronsert, P., Bulten, J., Hirschfeld, M., Colas, E., Gil-Moreno, A., Garcia, A., Mancebo, G., Alameda, F., Trovik, J., Kopperud, R.K., Huvila, J., Schrauwen, S., Koskas, M., Walker, F., Weinberger, V., Minar, L., Jandakova, E., Snijders, M.P.M.L., Erp, S. van, Matias-Guiu, X., Salvesen, H.B., Amant, F., Massuger, L.F.A.G., and Pijnenborg, J.M.A.
Abstract: Contains fulltext : 165692.pdf (publisher's version ) (Open Access), BACKGROUND: Identification of aggressive endometrioid endometrial carcinomas (EECs) and non-endometrioid carcinomas (NEECs) is essential to improve outcome. L1 cell adhesion molecule (L1CAM) expression is a strong prognostic marker in stage I EECs, but less is known about L1CAM expression in advanced-stage EECs and NEECs. This study analyses L1CAM expression in a clinically representative cohort of endometrial carcinomas. METHODS: The expression of L1CAM was immunohistochemically determined in 1199 endometrial carcinomas, treated at one of the European Network for Individualized Treatment of Endometrial Cancer (ENITEC) centres. Staining was considered positive when >10% of the tumour cells expressed L1CAM. The association between L1CAM expression and several clincopathological characteristics and disease outcome was calculated. RESULTS: In all, L1CAM was expressed in 10% of the 935 stage I EECs, 18% of the 160 advanced stage EECs, and 75% of the 104 NEECs. The expression of L1CAM was associated with advanced stage, nodal involvement, high tumour grade, non-endometrioid histology, lymphovascular space invasion, and distant recurrences in all cases, and with reduced survival in the EECs, but not in the NEECs. CONCLUSIONS: The expression of L1CAM is a strong predictor of poor outcome in EECs, but not NEECs. It is strongly associated with non-endometrioid histology and distant spread, and could improve the postoperative selection of high-risk endometrial carcinomas. The value of L1CAM expression in the preoperative selection of high-risk endometrial carcinomas should be studied.
Published: 2016

15. Adult body mass index and risk of ovarian cancer by subtype: a Mendelian randomization study

Author: Dixon, S.C., Nagle, C.M., Thrift, A.P., Pharoah, P.D., Pearce, C.L., Zheng, W., Painter, J.N., Chenevix-Trench, G., Fasching, P.A., Beckmann, M.W., Lambrechts, D., Vergote, I., Lambrechts, S., Nieuwenhuysen, E. Van, Rossing, M.A., Doherty, J.A., Wicklund, K.G., Chang-Claude, J., Rudolph, A., Moysich, K.B., Odunsi, K., Goodman, M.T., Wilkens, L.R., Thompson, P.J., Shvetsov, Y.B., Dork, T., Park-Simon, T.W., Hillemanns, P., Bogdanova, N., Butzow, R., Nevanlinna, H., Pelttari, L.M., Leminen, A., Modugno, F., Ness, R.B., Edwards, R.P., Kelley, J.L., Heitz, F., Karlan, B.Y., Kjaer, S.K., Hogdall, E., Jensen, A., Goode, E.L., Fridley, B.L., Cunningham, J.M., Winham, S.J., Giles, G.G., Bruinsma, F., Milne, R.L., Southey, M.C., Hildebrandt, M.A.T., Wu, X., Lu, K.H., Liang, D., Levine, D.A., Bisogna, M., Schildkraut, J.M., Berchuck, A., Cramer, D.W, Terry, K.L., Bandera, E.V., Olson, S.H., Salvesen, H.B., Thomsen, L.C., Kopperud, R.K., Bjorge, L., Kiemeney, L.A.L.M., Massuger, L.F.A.G., Pejovic, T., Cook, L.S., Le, N.D., Swenerton, K.D., Brooks-Wilson, A., Kelemen, L.E., Lubinski, J., Huzarski, T., Gronwald, J., Menkiszak, J., Wentzensen, N., Brinton, L., Yang, H., Lissowska, J., Hogdall, C.K., Lundvall, L., Song, H., Tyrer, J.P., Campbell, I., Eccles, D., Paul, J., Glasspool, R., Siddiqui, N., Whittemore, A.S., Sieh, W., McGuire, V., Rothstein, J.H., Narod, S.A., Phelan, C., Risch, H.A., McLaughlin, J.R., Anton-Culver, H., et al., Dixon, S.C., Nagle, C.M., Thrift, A.P., Pharoah, P.D., Pearce, C.L., Zheng, W., Painter, J.N., Chenevix-Trench, G., Fasching, P.A., Beckmann, M.W., Lambrechts, D., Vergote, I., Lambrechts, S., Nieuwenhuysen, E. Van, Rossing, M.A., Doherty, J.A., Wicklund, K.G., Chang-Claude, J., Rudolph, A., Moysich, K.B., Odunsi, K., Goodman, M.T., Wilkens, L.R., Thompson, P.J., Shvetsov, Y.B., Dork, T., Park-Simon, T.W., Hillemanns, P., Bogdanova, N., Butzow, R., Nevanlinna, H., Pelttari, L.M., Leminen, A., Modugno, F., Ness, R.B., Edwards, R.P., Kelley, J.L., Heitz, F., Karlan, B.Y., Kjaer, S.K., Hogdall, E., Jensen, A., Goode, E.L., Fridley, B.L., Cunningham, J.M., Winham, S.J., Giles, G.G., Bruinsma, F., Milne, R.L., Southey, M.C., Hildebrandt, M.A.T., Wu, X., Lu, K.H., Liang, D., Levine, D.A., Bisogna, M., Schildkraut, J.M., Berchuck, A., Cramer, D.W, Terry, K.L., Bandera, E.V., Olson, S.H., Salvesen, H.B., Thomsen, L.C., Kopperud, R.K., Bjorge, L., Kiemeney, L.A.L.M., Massuger, L.F.A.G., Pejovic, T., Cook, L.S., Le, N.D., Swenerton, K.D., Brooks-Wilson, A., Kelemen, L.E., Lubinski, J., Huzarski, T., Gronwald, J., Menkiszak, J., Wentzensen, N., Brinton, L., Yang, H., Lissowska, J., Hogdall, C.K., Lundvall, L., Song, H., Tyrer, J.P., Campbell, I., Eccles, D., Paul, J., Glasspool, R., Siddiqui, N., Whittemore, A.S., Sieh, W., McGuire, V., Rothstein, J.H., Narod, S.A., Phelan, C., Risch, H.A., McLaughlin, J.R., and Anton-Culver, H., et al.
Abstract: Contains fulltext : 170949.pdf (publisher's version ) (Closed access), BACKGROUND: Observational studies have reported a positive association between body mass index (BMI) and ovarian cancer risk. However, questions remain as to whether this represents a causal effect, or holds for all histological subtypes. The lack of association observed for serous cancers may, for instance, be due to disease-associated weight loss. Mendelian randomization (MR) uses genetic markers as proxies for risk factors to overcome limitations of observational studies. We used MR to elucidate the relationship between BMI and ovarian cancer, hypothesizing that genetically predicted BMI would be associated with increased risk of non-high grade serous ovarian cancers (non-HGSC) but not HGSC. METHODS: We pooled data from 39 studies (14 047 cases, 23 003 controls) in the Ovarian Cancer Association Consortium. We constructed a weighted genetic risk score (GRS, partial F-statistic = 172), summing alleles at 87 single nucleotide polymorphisms previously associated with BMI, weighting by their published strength of association with BMI. Applying two-stage predictor-substitution MR, we used logistic regression to estimate study-specific odds ratios (OR) and 95% confidence intervals (CI) for the association between genetically predicted BMI and risk, and pooled these using random-effects meta-analysis. RESULTS: Higher genetically predicted BMI was associated with increased risk of non-HGSC (pooled OR = 1.29, 95% CI 1.03-1.61 per 5 units BMI) but not HGSC (pooled OR = 1.06, 95% CI 0.88-1.27). Secondary analyses stratified by behaviour/subtype suggested that, consistent with observational data, the association was strongest for low-grade/borderline serous cancers (OR = 1.93, 95% CI 1.33-2.81). CONCLUSIONS: Our data suggest that higher BMI increases risk of non-HGSC, but not the more common and aggressive HGSC subtype, confirming the observational evidence.
Published: 2016

16. Shared genetics underlying epidemiological association between endometriosis and ovarian cancer

Author: Lu, Y., Cuellar-Partida, G., Painter, J.N., Nyholt, D.R., Morris, A.P., Fasching, P.A., Hein, A., Burghaus, S., Beckmann, M.W., Lambrechts, D., Nieuwenhuysen, E. Van, Vergote, I., Vanderstichele, A., Doherty, J.A., Rossing, M.A., Wicklund, K.G., Chang-Claude, J., Eilber, U., Rudolph, A., Wang-Gohrke, S., Goodman, M.T., Bogdanova, N., Dork, T., Durst, M., Hillemanns, P., Runnebaum, I.B., Antonenkova, N., Butzow, R., Leminen, A., Nevanlinna, H., Pelttari, L.M., Edwards, R.P., Kelley, J.L., Modugno, F., Moysich, K.B., Ness, R.B., Cannioto, R., Hogdall, E., Jensen, A., Giles, G.G., Bruinsma, F., Kjaer, S.K., Hildebrandt, M.A., Liang, D., Lu, K.H., Wu, X., Bisogna, M., Dao, F., Levine, D.A., Cramer, D.W, Terry, K.L., Tworoger, S.S., Missmer, S., Bjorge, L., Salvesen, H.B., Kopperud, R.K., Bischof, K., Aben, K.K.H., Kiemeney, L.A.L.M., Massuger, L.F.A.G., Brooks-Wilson, A., Olson, S.H., McGuire, V., Rothstein, J.H., Sieh, W., Whittemore, A.S., Cook, L.S., Le, N.D., Gilks, C.B., Gronwald, J., Jakubowska, A., Lubinski, J., Gawelko, J., Song, H., Tyrer, J.P., Wentzensen, N., Brinton, L., Trabert, B., Lissowska, J., McLaughlin, J.R., Narod, S.A., Phelan, C., Anton-Culver, H., Ziogas, A., Eccles, D., Gayther, S.A., Gentry-Maharaj, A., Menon, U., Ramus, S.J., Wu, A.H., Dansonka-Mieszkowska, A., Kupryjanczyk, J., Timorek, A., Szafron, L., Cunningham, J.M., Fridley, B.L., Winham, S.J., Bandera, E.V., Poole, E.M., Morgan, T.K., et al., Lu, Y., Cuellar-Partida, G., Painter, J.N., Nyholt, D.R., Morris, A.P., Fasching, P.A., Hein, A., Burghaus, S., Beckmann, M.W., Lambrechts, D., Nieuwenhuysen, E. Van, Vergote, I., Vanderstichele, A., Doherty, J.A., Rossing, M.A., Wicklund, K.G., Chang-Claude, J., Eilber, U., Rudolph, A., Wang-Gohrke, S., Goodman, M.T., Bogdanova, N., Dork, T., Durst, M., Hillemanns, P., Runnebaum, I.B., Antonenkova, N., Butzow, R., Leminen, A., Nevanlinna, H., Pelttari, L.M., Edwards, R.P., Kelley, J.L., Modugno, F., Moysich, K.B., Ness, R.B., Cannioto, R., Hogdall, E., Jensen, A., Giles, G.G., Bruinsma, F., Kjaer, S.K., Hildebrandt, M.A., Liang, D., Lu, K.H., Wu, X., Bisogna, M., Dao, F., Levine, D.A., Cramer, D.W, Terry, K.L., Tworoger, S.S., Missmer, S., Bjorge, L., Salvesen, H.B., Kopperud, R.K., Bischof, K., Aben, K.K.H., Kiemeney, L.A.L.M., Massuger, L.F.A.G., Brooks-Wilson, A., Olson, S.H., McGuire, V., Rothstein, J.H., Sieh, W., Whittemore, A.S., Cook, L.S., Le, N.D., Gilks, C.B., Gronwald, J., Jakubowska, A., Lubinski, J., Gawelko, J., Song, H., Tyrer, J.P., Wentzensen, N., Brinton, L., Trabert, B., Lissowska, J., McLaughlin, J.R., Narod, S.A., Phelan, C., Anton-Culver, H., Ziogas, A., Eccles, D., Gayther, S.A., Gentry-Maharaj, A., Menon, U., Ramus, S.J., Wu, A.H., Dansonka-Mieszkowska, A., Kupryjanczyk, J., Timorek, A., Szafron, L., Cunningham, J.M., Fridley, B.L., Winham, S.J., Bandera, E.V., Poole, E.M., Morgan, T.K., and et al.
Abstract: Contains fulltext : 153959.pdf (publisher's version ) (Closed access), Epidemiological studies have demonstrated associations between endometriosis and certain histotypes of ovarian cancer, including clear cell, low-grade serous and endometrioid carcinomas. We aimed to determine whether the observed associations might be due to shared genetic aetiology. To address this, we used two endometriosis datasets genotyped on common arrays with full-genome coverage (3194 cases and 7060 controls) and a large ovarian cancer dataset genotyped on the customized Illumina Infinium iSelect (iCOGS) arrays (10 065 cases and 21 663 controls). Previous work has suggested that a large number of genetic variants contribute to endometriosis and ovarian cancer (all histotypes combined) susceptibility. Here, using the iCOGS data, we confirmed polygenic architecture for most histotypes of ovarian cancer. This led us to evaluate if the polygenic effects are shared across diseases. We found evidence for shared genetic risks between endometriosis and all histotypes of ovarian cancer, except for the intestinal mucinous type. Clear cell carcinoma showed the strongest genetic correlation with endometriosis (0.51, 95% CI = 0.18-0.84). Endometrioid and low-grade serous carcinomas had similar correlation coefficients (0.48, 95% CI = 0.07-0.89 and 0.40, 95% CI = 0.05-0.75, respectively). High-grade serous carcinoma, which often arises from the fallopian tubes, showed a weaker genetic correlation with endometriosis (0.25, 95% CI = 0.11-0.39), despite the absence of a known epidemiological association. These results suggest that the epidemiological association between endometriosis and ovarian adenocarcinoma may be attributable to shared genetic susceptibility loci.
Published: 2015

17. Shared genetics underlying epidemiological association between endometriosis and ovarian cancer

Author: Lu, Y., Cuellar-Partida, G., Painter, J.N., Nyholt, D.R., Morris, A.P., Fasching, P.A., Hein, A., Burghaus, S., Beckmann, M.W., Lambrechts, D., Nieuwenhuysen, E. Van, Vergote, I., Vanderstichele, A., Doherty, J.A., Rossing, M.A., Wicklund, K.G., Chang-Claude, J., Eilber, U., Rudolph, A., Wang-Gohrke, S., Goodman, M.T., Bogdanova, N., Dork, T., Durst, M., Hillemanns, P., Runnebaum, I.B., Antonenkova, N., Butzow, R., Leminen, A., Nevanlinna, H., Pelttari, L.M., Edwards, R.P., Kelley, J.L., Modugno, F., Moysich, K.B., Ness, R.B., Cannioto, R., Hogdall, E., Jensen, A., Giles, G.G., Bruinsma, F., Kjaer, S.K., Hildebrandt, M.A., Liang, D., Lu, K.H., Wu, X., Bisogna, M., Dao, F., Levine, D.A., Cramer, D.W, Terry, K.L., Tworoger, S.S., Missmer, S., Bjorge, L., Salvesen, H.B., Kopperud, R.K., Bischof, K., Aben, K.K.H., Kiemeney, L.A.L.M., Massuger, L.F.A.G., Brooks-Wilson, A., Olson, S.H., McGuire, V., Rothstein, J.H., Sieh, W., Whittemore, A.S., Cook, L.S., Le, N.D., Gilks, C.B., Gronwald, J., Jakubowska, A., Lubinski, J., Gawelko, J., Song, H., Tyrer, J.P., Wentzensen, N., Brinton, L., Trabert, B., Lissowska, J., McLaughlin, J.R., Narod, S.A., Phelan, C., Anton-Culver, H., Ziogas, A., Eccles, D., Gayther, S.A., Gentry-Maharaj, A., Menon, U., Ramus, S.J., Wu, A.H., Dansonka-Mieszkowska, A., Kupryjanczyk, J., Timorek, A., Szafron, L., Cunningham, J.M., Fridley, B.L., Winham, S.J., Bandera, E.V., Poole, E.M., Morgan, T.K., et al., Lu, Y., Cuellar-Partida, G., Painter, J.N., Nyholt, D.R., Morris, A.P., Fasching, P.A., Hein, A., Burghaus, S., Beckmann, M.W., Lambrechts, D., Nieuwenhuysen, E. Van, Vergote, I., Vanderstichele, A., Doherty, J.A., Rossing, M.A., Wicklund, K.G., Chang-Claude, J., Eilber, U., Rudolph, A., Wang-Gohrke, S., Goodman, M.T., Bogdanova, N., Dork, T., Durst, M., Hillemanns, P., Runnebaum, I.B., Antonenkova, N., Butzow, R., Leminen, A., Nevanlinna, H., Pelttari, L.M., Edwards, R.P., Kelley, J.L., Modugno, F., Moysich, K.B., Ness, R.B., Cannioto, R., Hogdall, E., Jensen, A., Giles, G.G., Bruinsma, F., Kjaer, S.K., Hildebrandt, M.A., Liang, D., Lu, K.H., Wu, X., Bisogna, M., Dao, F., Levine, D.A., Cramer, D.W, Terry, K.L., Tworoger, S.S., Missmer, S., Bjorge, L., Salvesen, H.B., Kopperud, R.K., Bischof, K., Aben, K.K.H., Kiemeney, L.A.L.M., Massuger, L.F.A.G., Brooks-Wilson, A., Olson, S.H., McGuire, V., Rothstein, J.H., Sieh, W., Whittemore, A.S., Cook, L.S., Le, N.D., Gilks, C.B., Gronwald, J., Jakubowska, A., Lubinski, J., Gawelko, J., Song, H., Tyrer, J.P., Wentzensen, N., Brinton, L., Trabert, B., Lissowska, J., McLaughlin, J.R., Narod, S.A., Phelan, C., Anton-Culver, H., Ziogas, A., Eccles, D., Gayther, S.A., Gentry-Maharaj, A., Menon, U., Ramus, S.J., Wu, A.H., Dansonka-Mieszkowska, A., Kupryjanczyk, J., Timorek, A., Szafron, L., Cunningham, J.M., Fridley, B.L., Winham, S.J., Bandera, E.V., Poole, E.M., Morgan, T.K., and et al.
Abstract: Contains fulltext : 153959.pdf (publisher's version ) (Closed access), Epidemiological studies have demonstrated associations between endometriosis and certain histotypes of ovarian cancer, including clear cell, low-grade serous and endometrioid carcinomas. We aimed to determine whether the observed associations might be due to shared genetic aetiology. To address this, we used two endometriosis datasets genotyped on common arrays with full-genome coverage (3194 cases and 7060 controls) and a large ovarian cancer dataset genotyped on the customized Illumina Infinium iSelect (iCOGS) arrays (10 065 cases and 21 663 controls). Previous work has suggested that a large number of genetic variants contribute to endometriosis and ovarian cancer (all histotypes combined) susceptibility. Here, using the iCOGS data, we confirmed polygenic architecture for most histotypes of ovarian cancer. This led us to evaluate if the polygenic effects are shared across diseases. We found evidence for shared genetic risks between endometriosis and all histotypes of ovarian cancer, except for the intestinal mucinous type. Clear cell carcinoma showed the strongest genetic correlation with endometriosis (0.51, 95% CI = 0.18-0.84). Endometrioid and low-grade serous carcinomas had similar correlation coefficients (0.48, 95% CI = 0.07-0.89 and 0.40, 95% CI = 0.05-0.75, respectively). High-grade serous carcinoma, which often arises from the fallopian tubes, showed a weaker genetic correlation with endometriosis (0.25, 95% CI = 0.11-0.39), despite the absence of a known epidemiological association. These results suggest that the epidemiological association between endometriosis and ovarian adenocarcinoma may be attributable to shared genetic susceptibility loci.
Published: 2015

18. Shared genetics underlying epidemiological association between endometriosis and ovarian cancer

Author: Lu, Y., Cuellar-Partida, G., Painter, J.N., Nyholt, D.R., Morris, A.P., Fasching, P.A., Hein, A., Burghaus, S., Beckmann, M.W., Lambrechts, D., Nieuwenhuysen, E. Van, Vergote, I., Vanderstichele, A., Doherty, J.A., Rossing, M.A., Wicklund, K.G., Chang-Claude, J., Eilber, U., Rudolph, A., Wang-Gohrke, S., Goodman, M.T., Bogdanova, N., Dork, T., Durst, M., Hillemanns, P., Runnebaum, I.B., Antonenkova, N., Butzow, R., Leminen, A., Nevanlinna, H., Pelttari, L.M., Edwards, R.P., Kelley, J.L., Modugno, F., Moysich, K.B., Ness, R.B., Cannioto, R., Hogdall, E., Jensen, A., Giles, G.G., Bruinsma, F., Kjaer, S.K., Hildebrandt, M.A., Liang, D., Lu, K.H., Wu, X., Bisogna, M., Dao, F., Levine, D.A., Cramer, D.W, Terry, K.L., Tworoger, S.S., Missmer, S., Bjorge, L., Salvesen, H.B., Kopperud, R.K., Bischof, K., Aben, K.K.H., Kiemeney, L.A.L.M., Massuger, L.F.A.G., Brooks-Wilson, A., Olson, S.H., McGuire, V., Rothstein, J.H., Sieh, W., Whittemore, A.S., Cook, L.S., Le, N.D., Gilks, C.B., Gronwald, J., Jakubowska, A., Lubinski, J., Gawelko, J., Song, H., Tyrer, J.P., Wentzensen, N., Brinton, L., Trabert, B., Lissowska, J., McLaughlin, J.R., Narod, S.A., Phelan, C., Anton-Culver, H., Ziogas, A., Eccles, D., Gayther, S.A., Gentry-Maharaj, A., Menon, U., Ramus, S.J., Wu, A.H., Dansonka-Mieszkowska, A., Kupryjanczyk, J., Timorek, A., Szafron, L., Cunningham, J.M., Fridley, B.L., Winham, S.J., Bandera, E.V., Poole, E.M., Morgan, T.K., et al., Lu, Y., Cuellar-Partida, G., Painter, J.N., Nyholt, D.R., Morris, A.P., Fasching, P.A., Hein, A., Burghaus, S., Beckmann, M.W., Lambrechts, D., Nieuwenhuysen, E. Van, Vergote, I., Vanderstichele, A., Doherty, J.A., Rossing, M.A., Wicklund, K.G., Chang-Claude, J., Eilber, U., Rudolph, A., Wang-Gohrke, S., Goodman, M.T., Bogdanova, N., Dork, T., Durst, M., Hillemanns, P., Runnebaum, I.B., Antonenkova, N., Butzow, R., Leminen, A., Nevanlinna, H., Pelttari, L.M., Edwards, R.P., Kelley, J.L., Modugno, F., Moysich, K.B., Ness, R.B., Cannioto, R., Hogdall, E., Jensen, A., Giles, G.G., Bruinsma, F., Kjaer, S.K., Hildebrandt, M.A., Liang, D., Lu, K.H., Wu, X., Bisogna, M., Dao, F., Levine, D.A., Cramer, D.W, Terry, K.L., Tworoger, S.S., Missmer, S., Bjorge, L., Salvesen, H.B., Kopperud, R.K., Bischof, K., Aben, K.K.H., Kiemeney, L.A.L.M., Massuger, L.F.A.G., Brooks-Wilson, A., Olson, S.H., McGuire, V., Rothstein, J.H., Sieh, W., Whittemore, A.S., Cook, L.S., Le, N.D., Gilks, C.B., Gronwald, J., Jakubowska, A., Lubinski, J., Gawelko, J., Song, H., Tyrer, J.P., Wentzensen, N., Brinton, L., Trabert, B., Lissowska, J., McLaughlin, J.R., Narod, S.A., Phelan, C., Anton-Culver, H., Ziogas, A., Eccles, D., Gayther, S.A., Gentry-Maharaj, A., Menon, U., Ramus, S.J., Wu, A.H., Dansonka-Mieszkowska, A., Kupryjanczyk, J., Timorek, A., Szafron, L., Cunningham, J.M., Fridley, B.L., Winham, S.J., Bandera, E.V., Poole, E.M., Morgan, T.K., and et al.
Abstract: Contains fulltext : 153959.pdf (publisher's version ) (Closed access), Epidemiological studies have demonstrated associations between endometriosis and certain histotypes of ovarian cancer, including clear cell, low-grade serous and endometrioid carcinomas. We aimed to determine whether the observed associations might be due to shared genetic aetiology. To address this, we used two endometriosis datasets genotyped on common arrays with full-genome coverage (3194 cases and 7060 controls) and a large ovarian cancer dataset genotyped on the customized Illumina Infinium iSelect (iCOGS) arrays (10 065 cases and 21 663 controls). Previous work has suggested that a large number of genetic variants contribute to endometriosis and ovarian cancer (all histotypes combined) susceptibility. Here, using the iCOGS data, we confirmed polygenic architecture for most histotypes of ovarian cancer. This led us to evaluate if the polygenic effects are shared across diseases. We found evidence for shared genetic risks between endometriosis and all histotypes of ovarian cancer, except for the intestinal mucinous type. Clear cell carcinoma showed the strongest genetic correlation with endometriosis (0.51, 95% CI = 0.18-0.84). Endometrioid and low-grade serous carcinomas had similar correlation coefficients (0.48, 95% CI = 0.07-0.89 and 0.40, 95% CI = 0.05-0.75, respectively). High-grade serous carcinoma, which often arises from the fallopian tubes, showed a weaker genetic correlation with endometriosis (0.25, 95% CI = 0.11-0.39), despite the absence of a known epidemiological association. These results suggest that the epidemiological association between endometriosis and ovarian adenocarcinoma may be attributable to shared genetic susceptibility loci.
Published: 2015

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18 results on '"Kopperud R.K."'

1. Cross-Cancer Genome-Wide Association Study of Endometrial Cancer and Epithelial Ovarian Cancer Identifies Genetic Risk Regions Associated with Risk of Both Cancers.

2. Cross-Cancer Genome-Wide Association Study of Endometrial Cancer and Epithelial Ovarian Cancer Identifies Genetic Risk Regions Associated with Risk of Both Cancers.

3. Expression of L1CAM in curettage or high L1CAM level in preoperative blood samples predicts lymph node metastases and poor outcome in endometrial cancer patients

4. Identification of 12 new susceptibility loci for different histotypes of epithelial ovarian cancer

5. Expression of L1CAM in curettage or high L1CAM level in preoperative blood samples predicts lymph node metastases and poor outcome in endometrial cancer patients

6. L1CAM expression in endometrial carcinomas: an ENITEC collaboration study

7. Assessing the genetic architecture of epithelial ovarian cancer histological subtypes

8. Adult body mass index and risk of ovarian cancer by subtype: a Mendelian randomization study

9. Association of vitamin D levels and risk of ovarian cancer: a Mendelian randomization study

10. L1CAM expression in endometrial carcinomas: an ENITEC collaboration study

11. Assessing the genetic architecture of epithelial ovarian cancer histological subtypes

12. Adult body mass index and risk of ovarian cancer by subtype: a Mendelian randomization study

13. Association of vitamin D levels and risk of ovarian cancer: a Mendelian randomization study

14. L1CAM expression in endometrial carcinomas: an ENITEC collaboration study

15. Adult body mass index and risk of ovarian cancer by subtype: a Mendelian randomization study

16. Shared genetics underlying epidemiological association between endometriosis and ovarian cancer

17. Shared genetics underlying epidemiological association between endometriosis and ovarian cancer

18. Shared genetics underlying epidemiological association between endometriosis and ovarian cancer

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18 results on '"Kopperud R.K."'

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