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  1. Article ; Online: Offspring sex and risk of epithelial ovarian cancer: a multinational pooled analysis of 12 case-control studies.

    Modugno, Francesmary / Fu, Zhuxuan / Jordan, Susan J / Group, Aocs / Chang-Claude, Jenny / Fortner, Renée T / Goodman, Marc T / Moysich, Kirsten B / Schildkraut, Joellen M / Berchuck, Andrew / Bandera, Elisa V / Qin, Bo / Sutphen, Rebecca / McLaughlin, John R / Menon, Usha / Ramus, Susan J / Gayther, Simon A / Gentry-Maharaj, Aleksandra / Karpinskyj, Chloe /
    Pearce, Celeste L / Wu, Anna H / Risch, Harvey A / Webb, Penelope M

    European journal of epidemiology

    2020  Volume 35, Issue 11, Page(s) 1025–1042

    Abstract: While childbearing protects against risk of epithelial ovarian cancer (EOC), few studies have explored the impact on maternal EOC risk of sex of offspring, which may affect the maternal environment during pregnancy. We performed a pooled analysis among ... ...

    Abstract While childbearing protects against risk of epithelial ovarian cancer (EOC), few studies have explored the impact on maternal EOC risk of sex of offspring, which may affect the maternal environment during pregnancy. We performed a pooled analysis among parous participants from 12 case-controls studies comprising 6872 EOC patients and 9101 controls. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated using multivariable logistic regression for case-control associations and polytomous logistic regression for histotype-specific associations, all adjusted for potential confounders. In general, no associations were found between offspring sex and EOC risk. However, compared to bearing only female offspring, bearing one or more male offspring was associated with increased risk of mucinous EOC (OR = 1.45; 95% CI = 1.01-2.07), which appeared to be limited to women reporting menarche before age 13 compared to later menarche (OR = 1.71 vs 0.99; P-interaction = 0.02). Bearing increasing numbers of male offspring was associated with greater risks of mucinous tumors (OR = 1.31, 1.84, 2.31, for 1, 2 and 3 or more male offspring, respectively; trend-p = 0.005). Stratifying by hormonally-associated conditions suggested that compared to bearing all female offspring, bearing a male offspring was associated with lower risk of endometrioid cancer among women with a history of adult acne, hirsutism, or polycystic ovary syndrome (OR = 0.49, 95% CI = 0.28-0.83) but with higher risk among women without any of those conditions (OR = 1.64 95% CI = 1.14-2.34; P-interaction = 0.003). Offspring sex influences the childbearing-EOC risk relationship for specific histotypes and conditions. These findings support the differing etiologic origins of EOC histotypes and highlight the importance of EOC histotype-specific epidemiologic studies. These findings also suggest the need to better understand how pregnancy affects EOC risk.
    MeSH term(s) Adult ; Carcinoma, Ovarian Epithelial/etiology ; Carcinoma, Ovarian Epithelial/pathology ; Endometriosis/etiology ; Endometriosis/pathology ; Female ; Gender Identity ; Humans ; Infant, Newborn ; Male ; Middle Aged ; Ovarian Neoplasms/etiology ; Ovarian Neoplasms/pathology ; Pregnancy
    Language English
    Publishing date 2020-09-21
    Publishing country Netherlands
    Document type Journal Article ; Meta-Analysis
    ZDB-ID 632614-6
    ISSN 1573-7284 ; 0393-2990
    ISSN (online) 1573-7284
    ISSN 0393-2990
    DOI 10.1007/s10654-020-00682-9
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article ; Online: Population-based targeted sequencing of 54 candidate genes identifies

    Song, Honglin / Dicks, Ed M / Tyrer, Jonathan / Intermaggio, Maria / Chenevix-Trench, Georgia / Bowtell, David D / Traficante, Nadia / Group, Aocs / Brenton, James / Goranova, Teodora / Hosking, Karen / Piskorz, Anna / van Oudenhove, Elke / Doherty, Jen / Harris, Holly R / Rossing, Mary Anne / Duerst, Matthias / Dork, Thilo / Bogdanova, Natalia V /
    Modugno, Francesmary / Moysich, Kirsten / Odunsi, Kunle / Ness, Roberta / Karlan, Beth Y / Lester, Jenny / Jensen, Allan / Krüger Kjaer, Susanne / Høgdall, Estrid / Campbell, Ian G / Lázaro, Conxi / Pujara, Miguel Angel / Cunningham, Julie / Vierkant, Robert / Winham, Stacey J / Hildebrandt, Michelle / Huff, Chad / Li, Donghui / Wu, Xifeng / Yu, Yao / Permuth, Jennifer B / Levine, Douglas A / Schildkraut, Joellen M / Riggan, Marjorie J / Berchuck, Andrew / Webb, Penelope M / Group, Opal Study / Cybulski, Cezary / Gronwald, Jacek / Jakubowska, Anna / Lubinski, Jan / Alsop, Jennifer / Harrington, Patricia / Chan, Isaac / Menon, Usha / Pearce, Celeste L / Wu, Anna H / de Fazio, Anna / Kennedy, Catherine J / Goode, Ellen / Ramus, Susan / Gayther, Simon / Pharoah, Paul

    Journal of medical genetics

    2020  Volume 58, Issue 5, Page(s) 305–313

    Abstract: Purpose: The known epithelial ovarian cancer (EOC) susceptibility genes account for less than 50% of the heritable risk of ovarian cancer suggesting that other susceptibility genes exist. The aim of this study was to evaluate the contribution to ovarian ...

    Abstract Purpose: The known epithelial ovarian cancer (EOC) susceptibility genes account for less than 50% of the heritable risk of ovarian cancer suggesting that other susceptibility genes exist. The aim of this study was to evaluate the contribution to ovarian cancer susceptibility of rare deleterious germline variants in a set of candidate genes.
    Methods: We sequenced the coding region of 54 candidate genes in 6385 invasive EOC cases and 6115 controls of broad European ancestry. Genes with an increased frequency of putative deleterious variants in cases versus controls were further examined in an independent set of 14 135 EOC cases and 28 655 controls from the Ovarian Cancer Association Consortium and the UK Biobank. For each gene, we estimated the EOC risks and evaluated associations between germline variant status and clinical characteristics.
    Results: The ORs associated for high-grade serous ovarian cancer were 3.01 for
    Conclusions: We have found strong evidence that carriers of
    MeSH term(s) Case-Control Studies ; Fanconi Anemia Complementation Group N Protein/genetics ; Female ; Genetic Predisposition to Disease ; Genetic Variation ; Humans ; Ovarian Neoplasms/genetics ; Risk Assessment
    Chemical Substances Fanconi Anemia Complementation Group N Protein ; PALB2 protein, human
    Language English
    Publishing date 2020-06-16
    Publishing country England
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't ; Research Support, U.S. Gov't, Non-P.H.S.
    ZDB-ID 220881-7
    ISSN 1468-6244 ; 0022-2593
    ISSN (online) 1468-6244
    ISSN 0022-2593
    DOI 10.1136/jmedgenet-2019-106739
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  3. Article ; Online: Germline whole exome sequencing and large-scale replication identifies

    Dicks, Ed / Song, Honglin / Ramus, Susan J / Oudenhove, Elke Van / Tyrer, Jonathan P / Intermaggio, Maria P / Kar, Siddhartha / Harrington, Patricia / Bowtell, David D / Group, Aocs Study / Cicek, Mine S / Cunningham, Julie M / Fridley, Brooke L / Alsop, Jennifer / Jimenez-Linan, Mercedes / Piskorz, Anna / Goranova, Teodora / Kent, Emma / Siddiqui, Nadeem /
    Paul, James / Crawford, Robin / Poblete, Samantha / Lele, Shashi / Sucheston-Campbell, Lara / Moysich, Kirsten B / Sieh, Weiva / McGuire, Valerie / Lester, Jenny / Odunsi, Kunle / Whittemore, Alice S / Bogdanova, Natalia / Dürst, Matthias / Hillemanns, Peter / Karlan, Beth Y / Gentry-Maharaj, Aleksandra / Menon, Usha / Tischkowitz, Marc / Levine, Douglas / Brenton, James D / Dörk, Thilo / Goode, Ellen L / Gayther, Simon A / Pharoah, D P Paul

    Oncotarget

    2017  Volume 8, Issue 31, Page(s) 50930–50940

    Abstract: We analyzed whole exome sequencing data in germline DNA from 412 high grade serous ovarian cancer (HGSOC) cases from The Cancer Genome Atlas Project and identified 5,517 genes harboring a predicted deleterious germline coding mutation in at least one ... ...

    Abstract We analyzed whole exome sequencing data in germline DNA from 412 high grade serous ovarian cancer (HGSOC) cases from The Cancer Genome Atlas Project and identified 5,517 genes harboring a predicted deleterious germline coding mutation in at least one HGSOC case. Gene-set enrichment analysis showed enrichment for genes involved in DNA repair (p = 1.8×10
    Language English
    Publishing date 2017-03-03
    Publishing country United States
    Document type Journal Article
    ZDB-ID 2560162-3
    ISSN 1949-2553 ; 1949-2553
    ISSN (online) 1949-2553
    ISSN 1949-2553
    DOI 10.18632/oncotarget.15871
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  4. Article ; Online: Analyses of germline variants associated with ovarian cancer survival identify functional candidates at the 1q22 and 19p12 outcome loci.

    Glubb, Dylan M / Johnatty, Sharon E / Quinn, Michael C J / O'Mara, Tracy A / Tyrer, Jonathan P / Gao, Bo / Fasching, Peter A / Beckmann, Matthias W / Lambrechts, Diether / Vergote, Ignace / Velez Edwards, Digna R / Beeghly-Fadiel, Alicia / Benitez, Javier / Garcia, Maria J / Goodman, Marc T / Thompson, Pamela J / Dörk, Thilo / Dürst, Matthias / Modungo, Francesmary /
    Moysich, Kirsten / Heitz, Florian / du Bois, Andreas / Pfisterer, Jacobus / Hillemanns, Peter / Karlan, Beth Y / Lester, Jenny / Goode, Ellen L / Cunningham, Julie M / Winham, Stacey J / Larson, Melissa C / McCauley, Bryan M / Kjær, Susanne Krüger / Jensen, Allan / Schildkraut, Joellen M / Berchuck, Andrew / Cramer, Daniel W / Terry, Kathryn L / Salvesen, Helga B / Bjorge, Line / Webb, Penny M / Grant, Peter / Pejovic, Tanja / Moffitt, Melissa / Hogdall, Claus K / Hogdall, Estrid / Paul, James / Glasspool, Rosalind / Bernardini, Marcus / Tone, Alicia / Huntsman, David / Woo, Michelle / Group, Aocs / deFazio, Anna / Kennedy, Catherine J / Pharoah, Paul D P / MacGregor, Stuart / Chenevix-Trench, Georgia

    Oncotarget

    2017  Volume 8, Issue 39, Page(s) 64670–64684

    Abstract: We previously identified associations with ovarian cancer outcome at five genetic loci. To identify putatively causal genetic variants and target genes, we prioritized two ovarian outcome loci (1q22 and 19p12) for further study. Bioinformatic and ... ...

    Abstract We previously identified associations with ovarian cancer outcome at five genetic loci. To identify putatively causal genetic variants and target genes, we prioritized two ovarian outcome loci (1q22 and 19p12) for further study. Bioinformatic and functional genetic analyses indicated that
    Language English
    Publishing date 2017-06-15
    Publishing country United States
    Document type Journal Article
    ZDB-ID 2560162-3
    ISSN 1949-2553 ; 1949-2553
    ISSN (online) 1949-2553
    ISSN 1949-2553
    DOI 10.18632/oncotarget.18501
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  5. Article ; Online: Development and Validation of the Gene Expression Predictor of High-grade Serous Ovarian Carcinoma Molecular SubTYPE (PrOTYPE).

    Talhouk, Aline / George, Joshy / Wang, Chen / Budden, Timothy / Tan, Tuan Zea / Chiu, Derek S / Kommoss, Stefan / Leong, Huei San / Chen, Stephanie / Intermaggio, Maria P / Gilks, Blake / Nazeran, Tayyebeh M / Volchek, Mila / Elatre, Wafaa / Bentley, Rex C / Senz, Janine / Lum, Amy / Chow, Veronica / Sudderuddin, Hanwei /
    Mackenzie, Robertson / Leong, Samuel C Y / Liu, Geyi / Johnson, Dustin / Chen, Billy / Group, Aocs / Alsop, Jennifer / Banerjee, Susana N / Behrens, Sabine / Bodelon, Clara / Brand, Alison H / Brinton, Louise / Carney, Michael E / Chiew, Yoke-Eng / Cushing-Haugen, Kara L / Cybulski, Cezary / Ennis, Darren / Fereday, Sian / Fortner, Renée T / García-Donas, Jesús / Gentry-Maharaj, Aleksandra / Glasspool, Rosalind / Goranova, Teodora / Greene, Casey S / Haluska, Paul / Harris, Holly R / Hendley, Joy / Hernandez, Brenda Y / Herpel, Esther / Jimenez-Linan, Mercedes / Karpinskyj, Chloe / Kaufmann, Scott H / Keeney, Gary L / Kennedy, Catherine J / Köbel, Martin / Koziak, Jennifer M / Larson, Melissa C / Lester, Jenny / Lewsley, Liz-Anne / Lissowska, Jolanta / Lubiński, Jan / Luk, Hugh / Macintyre, Geoff / Mahner, Sven / McNeish, Iain A / Menkiszak, Janusz / Nevins, Nikilyn / Osorio, Ana / Oszurek, Oleg / Palacios, José / Hinsley, Samantha / Pearce, Celeste L / Pike, Malcolm C / Piskorz, Anna M / Ray-Coquard, Isabelle / Rhenius, Valerie / Rodriguez-Antona, Cristina / Sharma, Raghwa / Sherman, Mark E / De Silva, Dilrini / Singh, Naveena / Sinn, Peter / Slamon, Dennis / Song, Honglin / Steed, Helen / Stronach, Euan A / Thompson, Pamela J / Tołoczko, Aleksandra / Trabert, Britton / Traficante, Nadia / Tseng, Chiu-Chen / Widschwendter, Martin / Wilkens, Lynne R / Winham, Stacey J / Winterhoff, Boris / Beeghly-Fadiel, Alicia / Benitez, Javier / Berchuck, Andrew / Brenton, James D / Brown, Robert / Chang-Claude, Jenny / Chenevix-Trench, Georgia / deFazio, Anna / Fasching, Peter A / García, María J / Gayther, Simon A / Goodman, Marc T / Gronwald, Jacek / Henderson, Michelle J / Karlan, Beth Y / Kelemen, Linda E / Menon, Usha / Orsulic, Sandra / Pharoah, Paul D P / Wentzensen, Nicolas / Wu, Anna H / Schildkraut, Joellen M / Rossing, Mary Anne / Konecny, Gottfried E / Huntsman, David G / Huang, Ruby Yun-Ju / Goode, Ellen L / Ramus, Susan J / Doherty, Jennifer A / Bowtell, David D / Anglesio, Michael S

    Clinical cancer research : an official journal of the American Association for Cancer Research

    2020  Volume 26, Issue 20, Page(s) 5411–5423

    Abstract: Purpose: Gene expression-based molecular subtypes of high-grade serous tubo-ovarian cancer (HGSOC), demonstrated across multiple studies, may provide improved stratification for molecularly targeted trials. However, evaluation of clinical utility has ... ...

    Abstract Purpose: Gene expression-based molecular subtypes of high-grade serous tubo-ovarian cancer (HGSOC), demonstrated across multiple studies, may provide improved stratification for molecularly targeted trials. However, evaluation of clinical utility has been hindered by nonstandardized methods, which are not applicable in a clinical setting. We sought to generate a clinical grade minimal gene set assay for classification of individual tumor specimens into HGSOC subtypes and confirm previously reported subtype-associated features.
    Experimental design: Adopting two independent approaches, we derived and internally validated algorithms for subtype prediction using published gene expression data from 1,650 tumors. We applied resulting models to NanoString data on 3,829 HGSOCs from the Ovarian Tumor Tissue Analysis consortium. We further developed, confirmed, and validated a reduced, minimal gene set predictor, with methods suitable for a single-patient setting.
    Results: Gene expression data were used to derive the predictor of high-grade serous ovarian carcinoma molecular subtype (PrOTYPE) assay. We established a
    Conclusions: We validated the PrOTYPE assay following the Institute of Medicine guidelines for the development of omics-based tests. This fully defined and locked-down clinical grade assay will enable trial design with molecular subtype stratification and allow for objective assessment of the predictive value of HGSOC molecular subtypes in precision medicine applications.
    MeSH term(s) Aged ; Algorithms ; Cystadenoma, Serous/classification ; Cystadenoma, Serous/genetics ; Cystadenoma, Serous/pathology ; Female ; Gene Expression Regulation, Neoplastic/genetics ; Humans ; Lymphocytes, Tumor-Infiltrating/pathology ; Middle Aged ; Neoplasm Grading ; Neoplasm Proteins/genetics ; Neoplasm, Residual/classification ; Neoplasm, Residual/genetics ; Neoplasm, Residual/pathology ; Ovarian Neoplasms/classification ; Ovarian Neoplasms/genetics ; Ovarian Neoplasms/pathology ; Transcriptome/genetics
    Chemical Substances Neoplasm Proteins
    Language English
    Publishing date 2020-06-17
    Publishing country United States
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't ; Research Support, U.S. Gov't, Non-P.H.S.
    ZDB-ID 1225457-5
    ISSN 1557-3265 ; 1078-0432
    ISSN (online) 1557-3265
    ISSN 1078-0432
    DOI 10.1158/1078-0432.CCR-20-0103
    Database MEDical Literature Analysis and Retrieval System OnLINE

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