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Article ; Online: Disentangling the relationships of body mass index and circulating sex hormone concentrations in mammographic density using Mendelian randomization.

Haas, Cameron B / Chen, Hongjie / Harrison, Tabitha / Fan, Shaoqi / Gago-Dominguez, Manuela / Castelao, Jose E / Bolla, Manjeet K / Wang, Qin / Dennis, Joe / Michailidou, Kyriaki / Dunning, Alison M / Easton, Douglas F / Antoniou, Antonis C / Hall, Per / Czene, Kamila / Andrulis, Irene L / Mulligan, Anna Marie / Milne, Roger L / Fasching, Peter A /

Breast cancer research and treatment

2024

Abstract: Purpose: Mammographic density phenotypes, adjusted for age and body mass index (BMI), are strong predictors of breast cancer risk. BMI is associated with mammographic density measures, but the role of circulating sex hormone concentrations is less clear. ...

Abstract	Purpose: Mammographic density phenotypes, adjusted for age and body mass index (BMI), are strong predictors of breast cancer risk. BMI is associated with mammographic density measures, but the role of circulating sex hormone concentrations is less clear. We investigated the relationship between BMI, circulating sex hormone concentrations, and mammographic density phenotypes using Mendelian randomization (MR). Methods: We applied two-sample MR approaches to assess the association between genetically predicted circulating concentrations of sex hormones [estradiol, testosterone, sex hormone-binding globulin (SHBG)], BMI, and mammographic density phenotypes (dense and non-dense area). We created instrumental variables from large European ancestry-based genome-wide association studies and applied estimates to mammographic density phenotypes in up to 14,000 women of European ancestry. We performed analyses overall and by menopausal status. Results: Genetically predicted BMI was positively associated with non-dense area (IVW: β = 1.79; 95% CI = 1.58, 2.00; p = 9.57 × 10 Conclusion: Our findings support a positive causal association between BMI and mammographic non-dense area and an inverse association between BMI and dense area. Evidence was weaker and inconsistent for a causal effect of circulating sex hormone concentrations on mammographic density phenotypes. Based on our findings, associations between circulating sex hormone concentrations and mammographic density phenotypes are weak at best.
Language	English
Publishing date	2024-04-24
Publishing country	Netherlands
Document type	Journal Article
ZDB-ID	604563-7
ISSN	1573-7217 ; 0167-6806
ISSN (online)	1573-7217
ISSN	0167-6806
DOI	10.1007/s10549-024-07306-w
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Article ; Online: Author Correction: Exome sequencing identifies breast cancer susceptibility genes and defines the contribution of coding variants to breast cancer risk.

Wilcox, Naomi / Dumont, Martine / González-Neira, Anna / Carvalho, Sara / Joly Beauparlant, Charles / Crotti, Marco / Luccarini, Craig / Soucy, Penny / Dubois, Stéphane / Nuñez-Torres, Rocio / Pita, Guillermo / Gardner, Eugene J / Dennis, Joe / Alonso, M Rosario / Álvarez, Nuria / Baynes, Caroline / Collin-Deschesnes, Annie Claude / Desjardins, Sylvie / Becher, Heiko /

Behrens, Sabine / Bolla, Manjeet K / Castelao, Jose E / Chang-Claude, Jenny / Cornelissen, Sten / Dörk, Thilo / Engel, Christoph / Gago-Dominguez, Manuela / Guénel, Pascal / Hadjisavvas, Andreas / Hahnen, Eric / Hartman, Mikael / Herráez, Belén / Jung, Audrey / Keeman, Renske / Kiechle, Marion / Li, Jingmei / Loizidou, Maria A / Lush, Michael / Michailidou, Kyriaki / Panayiotidis, Mihalis I / Sim, Xueling / Teo, Soo Hwang / Tyrer, Jonathan P / van der Kolk, Lizet E / Wahlström, Cecilia / Wang, Qin / Perry, John R B / Benitez, Javier / Schmidt, Marjanka K / Schmutzler, Rita K / Pharoah, Paul D P / Droit, Arnaud / Dunning, Alison M / Kvist, Anders / Devilee, Peter / Easton, Douglas F / Simard, Jacques

Nature genetics

2023 Volume 55, Issue 11, Page(s) 2009

Language	English
Publishing date	2023-09-26
Publishing country	United States
Document type	Published Erratum
ZDB-ID	1108734-1
ISSN	1546-1718 ; 1061-4036
ISSN (online)	1546-1718
ISSN	1061-4036
DOI	10.1038/s41588-023-01549-x
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Article ; Online: Exome sequencing identifies breast cancer susceptibility genes and defines the contribution of coding variants to breast cancer risk.

Nature genetics

2023 Volume 55, Issue 9, Page(s) 1435–1439

Abstract: Linkage and candidate gene studies have identified several breast cancer susceptibility genes, but the overall contribution of coding variation to breast cancer is unclear. To evaluate the role of rare coding variants more comprehensively, we performed a ...

Abstract	Linkage and candidate gene studies have identified several breast cancer susceptibility genes, but the overall contribution of coding variation to breast cancer is unclear. To evaluate the role of rare coding variants more comprehensively, we performed a meta-analysis across three large whole-exome sequencing datasets, containing 26,368 female cases and 217,673 female controls. Burden tests were performed for protein-truncating and rare missense variants in 15,616 and 18,601 genes, respectively. Associations between protein-truncating variants and breast cancer were identified for the following six genes at exome-wide significance (P < 2.5 × 10
MeSH term(s)	Female ; Humans ; Exome Sequencing ; Exome/genetics ; Mutation, Missense/genetics ; Neoplasms
Language	English
Publishing date	2023-08-17
Publishing country	United States
Document type	Meta-Analysis ; Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	1108734-1
ISSN	1546-1718 ; 1061-4036
ISSN (online)	1546-1718
ISSN	1061-4036
DOI	10.1038/s41588-023-01466-z
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Article: Spectrum and Frequency of Germline

Figlioli, Gisella / Billaud, Amandine / Wang, Qin / Bolla, Manjeet K / Dennis, Joe / Lush, Michael / Kvist, Anders / Adank, Muriel A / Ahearn, Thomas U / Antonenkova, Natalia N / Auvinen, Päivi / Behrens, Sabine / Bermisheva, Marina / Bogdanova, Natalia V / Bojesen, Stig E / Bonanni, Bernardo / Brüning, Thomas / Camp, Nicola J / Campbell, Archie /

Castelao, Jose E / Cessna, Melissa H / Nbcs Collaborators / Czene, Kamila / Devilee, Peter / Dörk, Thilo / Eriksson, Mikael / Fasching, Peter A / Flyger, Henrik / Gabrielson, Marike / Gago-Dominguez, Manuela / García-Closas, Montserrat / Glendon, Gord / Gómez Garcia, Encarna B / González-Neira, Anna / Grassmann, Felix / Guénel, Pascal / Hahnen, Eric / Hamann, Ute / Hillemanns, Peter / Hooning, Maartje J / Hoppe, Reiner / Howell, Anthony / Humphreys, Keith / kConFab Investigators / Jakubowska, Anna / Khusnutdinova, Elza K / Kristensen, Vessela N / Lindblom, Annika / Loizidou, Maria A / Lubiński, Jan / Mannermaa, Arto / Maurer, Tabea / Mavroudis, Dimitrios / Newman, William G / Obi, Nadia / Panayiotidis, Mihalis I / Radice, Paolo / Rashid, Muhammad U / Rhenius, Valerie / Ruebner, Matthias / Saloustros, Emmanouil / Sawyer, Elinor J / Schmidt, Marjanka K / Schmutzler, Rita K / Shah, Mitul / Southey, Melissa C / Tomlinson, Ian / Truong, Thérèse / van Veen, Elke M / Wendt, Camilla / Yang, Xiaohong R / Michailidou, Kyriaki / Dunning, Alison M / Pharoah, Paul D P / Easton, Douglas F / Andrulis, Irene L / Evans, D Gareth / Hollestelle, Antoinette / Chang-Claude, Jenny / Milne, Roger L / Peterlongo, Paolo

Cancers

2023 Volume 15, Issue 13

Abstract: ... ...

Abstract	FANCM
Language	English
Publishing date	2023-06-23
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2527080-1
ISSN	2072-6694
ISSN	2072-6694
DOI	10.3390/cancers15133313
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Article: Differences in polygenic score distributions in European ancestry populations: implications for breast cancer risk prediction.

Yiangou, Kristia / Mavaddat, Nasim / Dennis, Joe / Zanti, Maria / Wang, Qin / Bolla, Manjeet K / Abubakar, Mustapha / Ahearn, Thomas U / Andrulis, Irene L / Anton-Culver, Hoda / Antonenkova, Natalia N / Arndt, Volker / Aronson, Kristan J / Augustinsson, Annelie / Baten, Adinda / Behrens, Sabine / Bermisheva, Marina / de Gonzalez, Amy Berrington / Białkowska, Katarzyna /

Boddicker, Nicholas / Bodelon, Clara / Bogdanova, Natalia V / Bojesen, Stig E / Brantley, Kristen D / Brauch, Hiltrud / Brenner, Hermann / Camp, Nicola J / Canzian, Federico / Castelao, Jose E / Cessna, Melissa H / Chang-Claude, Jenny / Chenevix-Trench, Georgia / Chung, Wendy K / Colonna, Sarah V / Couch, Fergus J / Cox, Angela / Cross, Simon S / Czene, Kamila / Daly, Mary B / Devilee, Peter / Dörk, Thilo / Dunning, Alison M / Eccles, Diana M / Eliassen, A Heather / Engel, Christoph / Eriksson, Mikael / Evans, D Gareth / Fasching, Peter A / Fletcher, Olivia / Flyger, Henrik / Fritschi, Lin / Gago-Dominguez, Manuela / Gentry-Maharaj, Aleksandra / González-Neira, Anna / Guénel, Pascal / Hahnen, Eric / Haiman, Christopher A / Hamann, Ute / Hartikainen, Jaana M / Ho, Vikki / Hodge, James / Hollestelle, Antoinette / Honisch, Ellen / Hooning, Maartje J / Hoppe, Reiner / Hopper, John L / Howell, Sacha / Howell, Anthony / Jakovchevska, Simona / Jakubowska, Anna / Jernström, Helena / Johnson, Nichola / Kaaks, Rudolf / Khusnutdinova, Elza K / Kitahara, Cari M / Koutros, Stella / Kristensen, Vessela N / Lacey, James V / Lambrechts, Diether / Lejbkowicz, Flavio / Lindblom, Annika / Lush, Michael / Mannermaa, Arto / Mavroudis, Dimitrios / Menon, Usha / Murphy, Rachel A / Nevanlinna, Heli / Obi, Nadia / Offit, Kenneth / Park-Simon, Tjoung-Won / Patel, Alpa V / Peng, Cheng / Peterlongo, Paolo / Pita, Guillermo / Plaseska-Karanfilska, Dijana / Pylkäs, Katri / Radice, Paolo / Rashid, Muhammad U / Rennert, Gad / Roberts, Eleanor / Rodriguez, Juan / Romero, Atocha / Rosenberg, Efraim H / Saloustros, Emmanouil / Sandler, Dale P / Sawyer, Elinor J / Schmutzler, Rita K / Scott, Christopher G / Shu, Xiao-Ou / Southey, Melissa C / Stone, Jennifer / Taylor, Jack A / Teras, Lauren R / van de Beek, Irma / Willett, Walter / Winqvist, Robert / Zheng, Wei / Vachon, Celine M / Schmidt, Marjanka K / Hall, Per / MacInnis, Robert J / Milne, Roger L / Pharoah, Paul D P / Simard, Jacques / Antoniou, Antonis C / Easton, Douglas F / Michailidou, Kyriaki

medRxiv : the preprint server for health sciences

2024

Abstract: The 313-variant polygenic risk score ( ... ...

Abstract	The 313-variant polygenic risk score (PRS
Language	English
Publishing date	2024-02-13
Publishing country	United States
Document type	Preprint
DOI	10.1101/2024.02.12.24302043
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Article ; Online: Genetically Predicted Levels of DNA Methylation Biomarkers and Breast Cancer Risk: Data From 228 951 Women of European Descent.

Yang, Yaohua / Wu, Lang / Shu, Xiao-Ou / Cai, Qiuyin / Shu, Xiang / Li, Bingshan / Guo, Xingyi / Ye, Fei / Michailidou, Kyriaki / Bolla, Manjeet K / Wang, Qin / Dennis, Joe / Andrulis, Irene L / Brenner, Hermann / Chenevix-Trench, Georgia / Campa, Daniele / Castelao, Jose E / Gago-Dominguez, Manuela / Dörk, Thilo /

Hollestelle, Antoinette / Lophatananon, Artitaya / Muir, Kenneth / Neuhausen, Susan L / Olsson, Håkan / Sandler, Dale P / Simard, Jacques / Kraft, Peter / Pharoah, Paul D P / Easton, Douglas F / Zheng, Wei / Long, Jirong

Journal of the National Cancer Institute

2019 Volume 112, Issue 3, Page(s) 295–304

Abstract: Background: DNA methylation plays a critical role in breast cancer development. Previous studies have identified DNA methylation marks in white blood cells as promising biomarkers for breast cancer. However, these studies were limited by low statistical ...

Abstract	Background: DNA methylation plays a critical role in breast cancer development. Previous studies have identified DNA methylation marks in white blood cells as promising biomarkers for breast cancer. However, these studies were limited by low statistical power and potential biases. Using a new methodology, we investigated DNA methylation marks for their associations with breast cancer risk. Methods: Statistical models were built to predict levels of DNA methylation marks using genetic data and DNA methylation data from HumanMethylation450 BeadChip from the Framingham Heart Study (n = 1595). The prediction models were validated using data from the Women's Health Initiative (n = 883). We applied these models to genomewide association study (GWAS) data of 122 977 breast cancer patients and 105 974 controls to evaluate if the genetically predicted DNA methylation levels at CpG sites (CpGs) are associated with breast cancer risk. All statistical tests were two-sided. Results: Of the 62 938 CpG sites CpGs investigated, statistically significant associations with breast cancer risk were observed for 450 CpGs at a Bonferroni-corrected threshold of P less than 7.94 × 10-7, including 45 CpGs residing in 18 genomic regions, that have not previously been associated with breast cancer risk. Of the remaining 405 CpGs located within 500 kilobase flaking regions of 70 GWAS-identified breast cancer risk variants, the associations for 11 CpGs were independent of GWAS-identified variants. Integrative analyses of genetic, DNA methylation, and gene expression data found that 38 CpGs may affect breast cancer risk through regulating expression of 21 genes. Conclusion: Our new methodology can identify novel DNA methylation biomarkers for breast cancer risk and can be applied to other diseases.
MeSH term(s)	Biomarkers, Tumor/genetics ; Breast Neoplasms/epidemiology ; Breast Neoplasms/genetics ; Case-Control Studies ; CpG Islands ; DNA Methylation ; Female ; Genetic Predisposition to Disease ; Genome-Wide Association Study ; Humans ; Models, Genetic ; Models, Statistical ; Polymorphism, Single Nucleotide ; Predictive Value of Tests ; Risk ; Transcriptome ; White People/genetics ; White People/statistics & numerical data
Chemical Substances	Biomarkers, Tumor
Language	English
Publishing date	2019-05-29
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	2992-0
ISSN	1460-2105 ; 0027-8874 ; 0198-0157
ISSN (online)	1460-2105
ISSN	0027-8874 ; 0198-0157
DOI	10.1093/jnci/djz109
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Article ; Online: FANCM missense variants and breast cancer risk: a case-control association study of 75,156 European women.

Figlioli, Gisella / Billaud, Amandine / Ahearn, Thomas U / Antonenkova, Natalia N / Becher, Heiko / Beckmann, Matthias W / Behrens, Sabine / Benitez, Javier / Bermisheva, Marina / Blok, Marinus J / Bogdanova, Natalia V / Bonanni, Bernardo / Burwinkel, Barbara / Camp, Nicola J / Campbell, Archie / Castelao, Jose E / Cessna, Melissa H / Chanock, Stephen J / Czene, Kamila /

Devilee, Peter / Dörk, Thilo / Engel, Christoph / Eriksson, Mikael / Fasching, Peter A / Figueroa, Jonine D / Gabrielson, Marike / Gago-Dominguez, Manuela / García-Closas, Montserrat / González-Neira, Anna / Grassmann, Felix / Guénel, Pascal / Gündert, Melanie / Hadjisavvas, Andreas / Hahnen, Eric / Hall, Per / Hamann, Ute / Harrington, Patricia A / He, Wei / Hillemanns, Peter / Hollestelle, Antoinette / Hooning, Maartje J / Hoppe, Reiner / Howell, Anthony / Humphreys, Keith / Jager, Agnes / Jakubowska, Anna / Khusnutdinova, Elza K / Ko, Yon-Dschun / Kristensen, Vessela N / Lindblom, Annika / Lissowska, Jolanta / Lubiński, Jan / Mannermaa, Arto / Manoukian, Siranoush / Margolin, Sara / Mavroudis, Dimitrios / Newman, William G / Obi, Nadia / Panayiotidis, Mihalis I / Rashid, Muhammad U / Rhenius, Valerie / Rookus, Matti A / Saloustros, Emmanouil / Sawyer, Elinor J / Schmutzler, Rita K / Shah, Mitul / Sironen, Reijo / Southey, Melissa C / Suvanto, Maija / Tollenaar, Rob A E M / Tomlinson, Ian / Truong, Thérèse / van der Kolk, Lizet E / van Veen, Elke M / Wappenschmidt, Barbara / Yang, Xiaohong R / Bolla, Manjeet K / Dennis, Joe / Dunning, Alison M / Easton, Douglas F / Lush, Michael / Michailidou, Kyriaki / Pharoah, Paul D P / Wang, Qin / Adank, Muriel A / Schmidt, Marjanka K / Andrulis, Irene L / Chang-Claude, Jenny / Nevanlinna, Heli / Chenevix-Trench, Georgia / Evans, D Gareth / Milne, Roger L / Radice, Paolo / Peterlongo, Paolo

European journal of human genetics : EJHG

2023 Volume 31, Issue 5, Page(s) 578–587

Abstract: Evidence from literature, including the BRIDGES study, indicates that germline protein truncating variants (PTVs) in FANCM confer moderately increased risk of ER-negative and triple-negative breast cancer (TNBC), especially for women with a family ... ...

Abstract	Evidence from literature, including the BRIDGES study, indicates that germline protein truncating variants (PTVs) in FANCM confer moderately increased risk of ER-negative and triple-negative breast cancer (TNBC), especially for women with a family history of the disease. Association between FANCM missense variants (MVs) and breast cancer risk has been postulated. In this study, we further used the BRIDGES study to test 689 FANCM MVs for association with breast cancer risk, overall and in ER-negative and TNBC subtypes, in 39,885 cases (7566 selected for family history) and 35,271 controls of European ancestry. Sixteen common MVs were tested individually; the remaining rare 673 MVs were tested by burden analyses considering their position and pathogenicity score. We also conducted a meta-analysis of our results and those from published studies. We did not find evidence for association for any of the 16 variants individually tested. The rare MVs were significantly associated with increased risk of ER-negative breast cancer by burden analysis comparing familial cases to controls (OR = 1.48; 95% CI 1.07-2.04; P = 0.017). Higher ORs were found for the subgroup of MVs located in functional domains or predicted to be pathogenic. The meta-analysis indicated that FANCM MVs overall are associated with breast cancer risk (OR = 1.22; 95% CI 1.08-1.38; P = 0.002). Our results support the definition from previous analyses of FANCM as a moderate-risk breast cancer gene and provide evidence that FANCM MVs could be low/moderate risk factors for ER-negative and TNBC subtypes. Further genetic and functional analyses are necessary to clarify better the increased risks due to FANCM MVs.
MeSH term(s)	Humans ; Female ; Breast Neoplasms/genetics ; DNA Helicases/genetics ; Triple Negative Breast Neoplasms/genetics ; Genetic Predisposition to Disease
Chemical Substances	FANCM protein, human (EC 3.6.1.-) ; DNA Helicases (EC 3.6.4.-)
Language	English
Publishing date	2023-01-27
Publishing country	England
Document type	Meta-Analysis ; Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't ; Research Support, U.S. Gov't, P.H.S.
ZDB-ID	1141470-4
ISSN	1476-5438 ; 1018-4813
ISSN (online)	1476-5438
ISSN	1018-4813
DOI	10.1038/s41431-022-01257-w
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Article ; Online: Evaluation of associations between genetically predicted circulating protein biomarkers and breast cancer risk.

Shu, Xiang / Bao, Jiandong / Wu, Lang / Long, Jirong / Shu, Xiao-Ou / Guo, Xingyi / Yang, Yaohua / Michailidou, Kyriaki / Bolla, Manjeet K / Wang, Qin / Dennis, Joe / Andrulis, Irene L / Castelao, Jose E / Dörk, Thilo / Gago-Dominguez, Manuela / García-Closas, Montserrat / Giles, Graham G / Lophatananon, Artitaya / Muir, Kenneth /

Olsson, Håkan / Rennert, Gadi / Saloustros, Emmanouil / Scott, Rodney J / Southey, Melissa C / Pharoah, Paul D P / Milne, Roger L / Kraft, Peter / Simard, Jacques / Easton, Douglas F / Zheng, Wei

International journal of cancer

2019 Volume 146, Issue 8, Page(s) 2130–2138

Abstract: A small number of circulating proteins have been reported to be associated with breast cancer risk, with inconsistent results. Herein, we attempted to identify novel protein biomarkers for breast cancer via the integration of genomics and proteomics data. ...

Abstract	A small number of circulating proteins have been reported to be associated with breast cancer risk, with inconsistent results. Herein, we attempted to identify novel protein biomarkers for breast cancer via the integration of genomics and proteomics data. In the Breast Cancer Association Consortium (BCAC), with 122,977 cases and 105,974 controls of European descendants, we evaluated the associations of the genetically predicted concentrations of >1,400 circulating proteins with breast cancer risk. We used data from a large-scale protein quantitative trait loci (pQTL) analysis as our study instrument. Summary statistics for these pQTL variants related to breast cancer risk were obtained from the BCAC and used to estimate odds ratios (OR) for each protein using the inverse-variance weighted method. We identified 56 proteins significantly associated with breast cancer risk by instrumental analysis (false discovery rate <0.05). Of these, the concentrations of 32 were influenced by variants close to a breast cancer susceptibility locus (ABO, 9q34.2). Many of these proteins, such as insulin receptor, insulin-like growth factor receptor 1 and other membrane receptors (OR: 0.82-1.18, p values: 6.96 × 10
MeSH term(s)	Biomarkers, Tumor/blood ; Biomarkers, Tumor/genetics ; Breast Neoplasms/blood ; Breast Neoplasms/genetics ; Case-Control Studies ; Female ; Genetic Predisposition to Disease ; Humans ; Neoplasm Proteins/blood ; Neoplasm Proteins/genetics ; Quantitative Trait Loci
Chemical Substances	Biomarkers, Tumor ; Neoplasm Proteins
Language	English
Publishing date	2019-07-16
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	218257-9
ISSN	1097-0215 ; 0020-7136
ISSN (online)	1097-0215
ISSN	0020-7136
DOI	10.1002/ijc.32542
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Article ; Online: The impact of coding germline variants on contralateral breast cancer risk and survival.

Morra, Anna / Mavaddat, Nasim / Muranen, Taru A / Ahearn, Thomas U / Allen, Jamie / Andrulis, Irene L / Auvinen, Päivi / Becher, Heiko / Behrens, Sabine / Blomqvist, Carl / Bojesen, Stig E / Bolla, Manjeet K / Brauch, Hiltrud / Camp, Nicola J / Carvalho, Sara / Castelao, Jose E / Cessna, Melissa H / Chang-Claude, Jenny / Chenevix-Trench, Georgia /

Czene, Kamila / Decker, Brennan / Dennis, Joe / Dörk, Thilo / Dorling, Leila / Dunning, Alison M / Ekici, Arif B / Eriksson, Mikael / Evans, D Gareth / Fasching, Peter A / Figueroa, Jonine D / Flyger, Henrik / Gago-Dominguez, Manuela / García-Closas, Montserrat / Geurts-Giele, Willemina R R / Giles, Graham G / Guénel, Pascal / Gündert, Melanie / Hahnen, Eric / Hall, Per / Hamann, Ute / Harrington, Patricia A / He, Wei / Heikkilä, Päivi / Hooning, Maartje J / Hoppe, Reiner / Howell, Anthony / Humphreys, Keith / Jakubowska, Anna / Jung, Audrey Y / Keeman, Renske / Kristensen, Vessela N / Lubiński, Jan / Mannermaa, Arto / Manoochehri, Mehdi / Manoukian, Siranoush / Margolin, Sara / Mavroudis, Dimitrios / Milne, Roger L / Mulligan, Anna Marie / Newman, William G / Park-Simon, Tjoung-Won / Peterlongo, Paolo / Pharoah, Paul D P / Rhenius, Valerie / Saloustros, Emmanouil / Sawyer, Elinor J / Schmutzler, Rita K / Shah, Mitul / Spurdle, Amanda B / Tomlinson, Ian / Truong, Thérèse / van Veen, Elke M / Vreeswijk, Maaike P G / Wang, Qin / Wendt, Camilla / Yang, Xiaohong R / Nevanlinna, Heli / Devilee, Peter / Easton, Douglas F / Schmidt, Marjanka K

American journal of human genetics

2023 Volume 110, Issue 3, Page(s) 475–486

Abstract: Evidence linking coding germline variants in breast cancer (BC)-susceptibility genes other than BRCA1, BRCA2, and CHEK2 with contralateral breast cancer (CBC) risk and breast cancer-specific survival (BCSS) is scarce. The aim of this study was to assess ... ...

Abstract	Evidence linking coding germline variants in breast cancer (BC)-susceptibility genes other than BRCA1, BRCA2, and CHEK2 with contralateral breast cancer (CBC) risk and breast cancer-specific survival (BCSS) is scarce. The aim of this study was to assess the association of protein-truncating variants (PTVs) and rare missense variants (MSVs) in nine known (ATM, BARD1, BRCA1, BRCA2, CHEK2, PALB2, RAD51C, RAD51D, and TP53) and 25 suspected BC-susceptibility genes with CBC risk and BCSS. Hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated with Cox regression models. Analyses included 34,401 women of European ancestry diagnosed with BC, including 676 CBCs and 3,449 BC deaths; the median follow-up was 10.9 years. Subtype analyses were based on estrogen receptor (ER) status of the first BC. Combined PTVs and pathogenic/likely pathogenic MSVs in BRCA1, BRCA2, and TP53 and PTVs in CHEK2 and PALB2 were associated with increased CBC risk [HRs (95% CIs): 2.88 (1.70-4.87), 2.31 (1.39-3.85), 8.29 (2.53-27.21), 2.25 (1.55-3.27), and 2.67 (1.33-5.35), respectively]. The strongest evidence of association with BCSS was for PTVs and pathogenic/likely pathogenic MSVs in BRCA2 (ER-positive BC) and TP53 and PTVs in CHEK2 [HRs (95% CIs): 1.53 (1.13-2.07), 2.08 (0.95-4.57), and 1.39 (1.13-1.72), respectively, after adjusting for tumor characteristics and treatment]. HRs were essentially unchanged when censoring for CBC, suggesting that these associations are not completely explained by increased CBC risk, tumor characteristics, or treatment. There was limited evidence of associations of PTVs and/or rare MSVs with CBC risk or BCSS for the 25 suspected BC genes. The CBC findings are relevant to treatment decisions, follow-up, and screening after BC diagnosis.
MeSH term(s)	Female ; Humans ; Breast Neoplasms/genetics ; Genes, BRCA2 ; Germ-Line Mutation ; Germ Cells ; Genetic Predisposition to Disease
Language	English
Publishing date	2023-02-23
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	219384-x
ISSN	1537-6605 ; 0002-9297
ISSN (online)	1537-6605
ISSN	0002-9297
DOI	10.1016/j.ajhg.2023.02.003
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Article ; Online: Water intake and bladder cancer risk in Los Angeles County.

Jiang, Xuejuan / Castelao, Jose E / Groshen, Susan / Cortessis, Victoria K / Shibata, Darryl K / Conti, David V / Gago-Dominguez, Manuela

International journal of cancer

2008 Volume 123, Issue 7, Page(s) 1649–1656

Abstract: The overall evidence of an association between fluid intake and bladder cancer is not entirely consistent. We examined the fluid intake-bladder cancer relationship in the Los Angeles bladder cancer case-control study. A total of 1,586 cases and their age- ...

Abstract	The overall evidence of an association between fluid intake and bladder cancer is not entirely consistent. We examined the fluid intake-bladder cancer relationship in the Los Angeles bladder cancer case-control study. A total of 1,586 cases and their age-, sex-, and race-matched neighborhood controls were interviewed in-person from 1987 to 1999. Information on total fluid intake was derived from the consumption of specific fluids including water, coffee, tea, alcohol, milk, juice, hot chocolate and soda. Total fluid intake was not associated with bladder cancer. Daily water intake was associated with a slight decrease in bladder cancer risk, with the protection more pronounced among women (p for trend = 0.039) than among men (p for trend = 0.62). Compared to drinking <1 glass of water per day, drinking > or =6 glasses/day was associated with 0.91 (95% confidence interval, 0.67-1.22) times the risk of bladder cancer among all subjects, 0.94 (0.67-1.32) times the risk among men, and 0.69 (0.36-1.33) times the risk among women. The water intake-bladder cancer association also seemed to be modified by daytime urination frequency with significant inverse association among subjects who urinated > or =6 times/day (p for trend = 0.015), but not among those who urinated less frequently. Similarly, the protection from water intake was confined to women who did not experience nocturia and to men who did. Results from our study suggest that water intake may be associated with a slight reduction in bladder cancer risk.
MeSH term(s)	Case-Control Studies ; Drinking ; Female ; Humans ; Los Angeles/epidemiology ; Male ; Risk Factors ; Urinary Bladder Neoplasms/etiology ; Water Supply
Language	English
Publishing date	2008-10-01
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	218257-9
ISSN	1097-0215 ; 0020-7136
ISSN (online)	1097-0215
ISSN	0020-7136
DOI	10.1002/ijc.23711
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Zs.A 478: Show issues			Location: Je nach Verfügbarkeit (siehe Angabe bei Bestand) bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular Jg. 1995 - 2021: Lesesall (1.OG) ab Jg. 2022: Lesesaal (EG)
Zs.MO 576: Show issues

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