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  1. Article: Bi-directional Mendelian randomization of epithelial ovarian cancer and schizophrenia and uni-directional Mendelian randomization of schizophrenia on circulating 1- or 2-glycerophosphocholine metabolites.

    Adams, Charleen D / Neuhausen, Susan L

    Molecular genetics and metabolism reports

    2019  Volume 21, Page(s) 100539

    Abstract: Most women with epithelial ovarian cancer (EOC) present with late-stage disease. As a result, globally, EOC is responsible for >150,000 deaths a year. Thus, a better understanding of risk factors for developing EOC is crucial for earlier screening and ... ...

    Abstract Most women with epithelial ovarian cancer (EOC) present with late-stage disease. As a result, globally, EOC is responsible for >150,000 deaths a year. Thus, a better understanding of risk factors for developing EOC is crucial for earlier screening and detection to improve survival. To that effort, there have been suggestions that there is an association of schizophrenia and cancer, possibly because metabolic changes are a hallmark of both cancer and schizophrenia (SZ). Perturbed choline metabolism has been documented in both diseases. Our objective was to use Mendelian randomization to evaluate whether SZ increased risk for developing EOC or the converse, and, whether SZ impacted 1- or 2-glycerophosphocholine (1- or 2-GPC) metabolites. We found that SZ conferred a weak but increased risk for EOC, but not the reverse (no evidence that EOC caused SZ). SZ was also causally associated with lower levels of two 1- or 2-GPC species and with suggestively lower levels in an additional three 1- or 2-GPCs. We postulate that perturbed choline metabolism in SZ may mimic or contribute to a "cholinic" phenotype, as observed in EOC cells.
    Language English
    Publishing date 2019-11-06
    Publishing country United States
    Document type Journal Article
    ZDB-ID 2821908-9
    ISSN 2214-4269
    ISSN 2214-4269
    DOI 10.1016/j.ymgmr.2019.100539
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article ; Online: Evaluating causal associations between chronotype and fatty acids and between fatty acids and type 2 diabetes: A Mendelian randomization study.

    Adams, Charleen D / Neuhausen, Susan L

    Nutrition, metabolism, and cardiovascular diseases : NMCD

    2019  Volume 29, Issue 11, Page(s) 1176–1184

    Abstract: Background and aims: Preference for activity in the morning or evening (chronotype) may impact type 2 diabetes (T2D) risk factors. Our objective was to use Mendelian randomization (MR) to evaluate whether there are causal links between chronotype and ... ...

    Abstract Background and aims: Preference for activity in the morning or evening (chronotype) may impact type 2 diabetes (T2D) risk factors. Our objective was to use Mendelian randomization (MR) to evaluate whether there are causal links between chronotype and one potential T2D risk factor, total fatty acids (TOTFA), and between TOTFA and T2D.
    Methods and results: We estimated the causal effect of: 1) morning chronotype on TOTFA; and 2) higher TOTFA on T2D. We found that: a) morning compared to evening chronotype was associated with lower TOTFA levels (inverse-weighted variance (IVW) estimate -0.21; 95% CI -0.38, -0.03; raw P = 0.02; FDR-corrected P 0.04) and b) elevated TOTFA levels were protective against T2D (IVW estimate -0.23; 95% CI -0.41, -0.05; raw P = 0.01; FDR-corrected P = 0.03). Based on this finding, we further hypothesized that healthy fats would show a similar pattern and performed MR of a) morning chronotype on omega-3 (Omega-3), monounsaturated (MUFA), and polyunsaturated (PUFA) fatty acids; and b) MR of each of these fat types on T2D. We observed the same mediating-type pattern for chronotype, MUFA, and T2D as we had for chronotype, TOTFA, and T2D, and morning chronotype was associated with lower Omega-3.
    Conclusion: Our findings provide suggestive, new information about relationships among chronotype, TOTFA, and T2D and about chronotype as a factor influencing Omega-3, MUFA, and TOTFA levels. In addition, we validated previous knowledge about MUFA and T2D. Morning chronotypes may predispose towards lower levels of TOTFA and some healthy fats, whereas higher levels of TOTFA and MUFA may protect against T2D.
    MeSH term(s) Activity Cycles/genetics ; Biomarkers/blood ; Diabetes Mellitus, Type 2/blood ; Diabetes Mellitus, Type 2/diagnosis ; Diabetes Mellitus, Type 2/genetics ; Diabetes Mellitus, Type 2/physiopathology ; Fatty Acids/blood ; Genetic Predisposition to Disease ; Humans ; Mendelian Randomization Analysis ; Phenotype ; Polymorphism, Single Nucleotide ; Prognosis ; Risk Assessment ; Risk Factors
    Chemical Substances Biomarkers ; Fatty Acids
    Language English
    Publishing date 2019-06-28
    Publishing country Netherlands
    Document type Comparative Study ; Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 1067704-5
    ISSN 1590-3729 ; 0939-4753
    ISSN (online) 1590-3729
    ISSN 0939-4753
    DOI 10.1016/j.numecd.2019.06.020
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  3. Article: Evaluating causal associations between chronotype and fatty acids and between fatty acids and type 2 diabetes: A Mendelian randomization study

    Adams, Charleen D / Neuhausen, Susan L

    The Italian Society of Diabetology, the Italian Society for the Study of Atherosclerosis, the Italian Society of Human Nutrition, and the Department of Clinical Medicine and Surgery, Federico II University Nutrition, metabolism, and cardiovascular diseases. 2019 Nov., v. 29, no. 11

    2019  

    Abstract: Preference for activity in the morning or evening (chronotype) may impact type 2 diabetes (T2D) risk factors. Our objective was to use Mendelian randomization (MR) to evaluate whether there are causal links between chronotype and one potential T2D risk ... ...

    Abstract Preference for activity in the morning or evening (chronotype) may impact type 2 diabetes (T2D) risk factors. Our objective was to use Mendelian randomization (MR) to evaluate whether there are causal links between chronotype and one potential T2D risk factor, total fatty acids (TOTFA), and between TOTFA and T2D.We estimated the causal effect of: 1) morning chronotype on TOTFA; and 2) higher TOTFA on T2D. We found that: a) morning compared to evening chronotype was associated with lower TOTFA levels (inverse-weighted variance (IVW) estimate −0.21; 95% CI −0.38, −0.03; raw P = 0.02; FDR-corrected P 0.04) and b) elevated TOTFA levels were protective against T2D (IVW estimate −0.23; 95% CI −0.41, −0.05; raw P = 0.01; FDR-corrected P = 0.03). Based on this finding, we further hypothesized that healthy fats would show a similar pattern and performed MR of a) morning chronotype on omega-3 (Omega-3), monounsaturated (MUFA), and polyunsaturated (PUFA) fatty acids; and b) MR of each of these fat types on T2D. We observed the same mediating-type pattern for chronotype, MUFA, and T2D as we had for chronotype, TOTFA, and T2D, and morning chronotype was associated with lower Omega-3.Our findings provide suggestive, new information about relationships among chronotype, TOTFA, and T2D and about chronotype as a factor influencing Omega-3, MUFA, and TOTFA levels. In addition, we validated previous knowledge about MUFA and T2D. Morning chronotypes may predispose towards lower levels of TOTFA and some healthy fats, whereas higher levels of TOTFA and MUFA may protect against T2D.
    Keywords cardiovascular diseases ; fatty acid composition ; metabolism ; noninsulin-dependent diabetes mellitus ; polyunsaturated fatty acids ; risk factors ; variance
    Language English
    Dates of publication 2019-11
    Size p. 1176-1184.
    Publishing place Elsevier B.V.
    Document type Article
    ZDB-ID 1067704-5
    ISSN 0939-4753
    ISSN 0939-4753
    DOI 10.1016/j.numecd.2019.06.020
    Database NAL-Catalogue (AGRICOLA)

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  4. Article ; Online: Reply to V. Fallet et al.

    Li, Shuai / Silvestri, Valentina / Rebbeck, Timothy R / Neuhausen, Susan L / Hopper, John L / Nielsen, Henriette Roed / Ottini, Laura / Antoniou, Antonis C

    Journal of clinical oncology : official journal of the American Society of Clinical Oncology

    2022  Volume 40, Issue 22, Page(s) 2509–2510

    Language English
    Publishing date 2022-05-12
    Publishing country United States
    Document type Research Support, Non-U.S. Gov't ; Letter ; Research Support, N.I.H., Extramural ; Comment
    ZDB-ID 604914-x
    ISSN 1527-7755 ; 0732-183X
    ISSN (online) 1527-7755
    ISSN 0732-183X
    DOI 10.1200/JCO.22.00782
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  5. Article: Erratum: Cancer screening and breast cancer family history in Spanish-speaking Hispanic/Latina women in California.

    Tamayo, Lizeth I / Perez, Fabian / Perez, Angelica / Hernandez, Miriam / Martinez, Alejandra / Huang, Xiaosong / Zavala, Valentina A / Ziv, Elad / Neuhausen, Susan L / Carvajal-Carmona, Luis G / Duron, Ysabel / Fejerman, Laura

    Frontiers in oncology

    2023  Volume 12, Page(s) 1087022

    Abstract: This corrects the article DOI: 10.3389/fonc.2022.940162.]. ...

    Abstract [This corrects the article DOI: 10.3389/fonc.2022.940162.].
    Language English
    Publishing date 2023-01-06
    Publishing country Switzerland
    Document type Published Erratum
    ZDB-ID 2649216-7
    ISSN 2234-943X
    ISSN 2234-943X
    DOI 10.3389/fonc.2022.1087022
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  6. Article ; Online: Mammary cell gene expression atlas links epithelial cell remodeling events to breast carcinogenesis.

    Saeki, Kohei / Chang, Gregory / Kanaya, Noriko / Wu, Xiwei / Wang, Jinhui / Bernal, Lauren / Ha, Desiree / Neuhausen, Susan L / Chen, Shiuan

    Communications biology

    2021  Volume 4, Issue 1, Page(s) 660

    Abstract: The female mammary epithelium undergoes reorganization during development, pregnancy, and menopause, linking higher risk with breast cancer development. To characterize these periods of complex remodeling, here we report integrated 50 K mouse and 24 K ... ...

    Abstract The female mammary epithelium undergoes reorganization during development, pregnancy, and menopause, linking higher risk with breast cancer development. To characterize these periods of complex remodeling, here we report integrated 50 K mouse and 24 K human mammary epithelial cell atlases obtained by single-cell RNA sequencing, which covers most lifetime stages. Our results indicate a putative trajectory that originates from embryonic mammary stem cells which differentiates into three epithelial lineages (basal, luminal hormone-sensing, and luminal alveolar), presumably arising from unipotent progenitors in postnatal glands. The lineage-specific genes infer cells of origin of breast cancer using The Cancer Genome Atlas data and single-cell RNA sequencing of human breast cancer, as well as the association of gland reorganization to different breast cancer subtypes. This comprehensive mammary cell gene expression atlas ( https://mouse-mammary-epithelium-integrated.cells.ucsc.edu ) presents insights into the impact of the internal and external stimuli on the mammary epithelium at an advanced resolution.
    MeSH term(s) Animals ; Breast/cytology ; Breast/metabolism ; Breast Neoplasms/etiology ; Breast Neoplasms/genetics ; Breast Neoplasms/pathology ; Carcinogenesis/genetics ; Cell Lineage/genetics ; Cell Transformation, Neoplastic/genetics ; Databases, Nucleic Acid/statistics & numerical data ; Epithelial Cells/cytology ; Epithelial Cells/metabolism ; Female ; Gene Expression Regulation, Neoplastic ; Humans ; Mammary Glands, Animal/cytology ; Mammary Glands, Animal/metabolism ; Mammary Neoplasms, Experimental/etiology ; Mammary Neoplasms, Experimental/genetics ; Mammary Neoplasms, Experimental/pathology ; Mice ; Mice, Inbred BALB C ; Pregnancy ; RNA-Seq/statistics & numerical data
    Language English
    Publishing date 2021-06-02
    Publishing country England
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
    ISSN 2399-3642
    ISSN (online) 2399-3642
    DOI 10.1038/s42003-021-02201-2
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  7. Article: Prostate cancer in young men represents a distinct clinical phenotype: gene expression signature to predict early metastases.

    Ding, Yuan C / Wu, Huiqing / Davicioni, Elai / Karnes, R Jeffrey / Klein, Eric A / Den, Robert B / Steele, Linda / Neuhausen, Susan L

    Journal of translational genetics and genomics

    2021  Volume 5, Page(s) 50–61

    Abstract: Aim: Several genomic signatures are available to predict Prostate Cancer (CaP) outcomes based on gene expression in prostate tissue. However, no signature was tailored to predict aggressive CaP in younger men. We attempted to develop a gene signature to ...

    Abstract Aim: Several genomic signatures are available to predict Prostate Cancer (CaP) outcomes based on gene expression in prostate tissue. However, no signature was tailored to predict aggressive CaP in younger men. We attempted to develop a gene signature to predict the development of metastatic CaP in young men.
    Methods: We measured genome-wide gene expression for 119 tumor and matched benign tissues from prostatectomies of men diagnosed at ≤ 50 years and > 70 years and identified age-related differentially expressed genes (DEGs) for tissue type and Gleason score. Age-related DEGs were selected using the improved Prediction Analysis of Microarray method (iPAM) to construct and validate a classifier to predict metastasis using gene expression data from 1,232 prostatectomies. Accuracy in predicting early metastasis was quantified by the area under the curve (AUC) of receiver operating characteristic (ROC), and abundance of immune cells in the tissue microenvironment was estimated using gene expression data.
    Results: Thirty-six age-related DEGs were selected for the iPAM classifier. The AUC of five-year survival ROC for the iPAM classifier was 0.87 (95%CI: 0.78-0.94) in young (≤ 55 years), 0.82 (95%CI: 0.76-0.88) in middle-aged (56-70 years), and 0.69 (95%CI: 0.55-0.69) in old (> 70 years) patients. Metastasis-associated immune responses in the tumor microenvironment were more pronounced in young and middle-aged patients than in old ones, potentially explaining the difference in accuracy of prediction among the groups.
    Conclusion: We developed a genomic classifier with high precision to predict early metastasis for younger CaP patients and identified age-related differences in immune response to metastasis development.
    Language English
    Publishing date 2021-03-09
    Publishing country United States
    Document type Journal Article
    ISSN 2578-5281
    ISSN 2578-5281
    DOI 10.20517/jtgg.2021.01
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  8. Article ; Online: Author Correction: Mammary cell gene expression atlas links epithelial cell remodeling events to breast carcinogenesis.

    Saeki, Kohei / Chang, Gregory / Kanaya, Noriko / Wu, Xiwei / Wang, Jinhui / Bernal, Lauren / Ha, Desiree / Neuhausen, Susan L / Chen, Shiuan

    Communications biology

    2021  Volume 4, Issue 1, Page(s) 892

    Language English
    Publishing date 2021-07-15
    Publishing country England
    Document type Published Erratum
    ISSN 2399-3642
    ISSN (online) 2399-3642
    DOI 10.1038/s42003-021-02424-3
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  9. Article ; Online: Genetics of gastric cancer: what do we know about the genetic risks?

    Slavin, Thomas Paul / Weitzel, Jeffrey N / Neuhausen, Susan L / Schrader, Kasmintan A / Oliveira, Carla / Karam, Rachid

    Translational gastroenterology and hepatology

    2019  Volume 4, Page(s) 55

    Abstract: An appreciable number of patients with gastric cancer have an underlying hereditary cancer susceptibility syndrome as the cause of their gastric cancer, particularly those with early onset gastric cancer or a family history of gastric or other cancers. ... ...

    Abstract An appreciable number of patients with gastric cancer have an underlying hereditary cancer susceptibility syndrome as the cause of their gastric cancer, particularly those with early onset gastric cancer or a family history of gastric or other cancers. Pathogenic germline variants in specific genes account for the known gastric cancer predisposition syndromes. Germline genetic testing can identify individuals and their family members who carry inherited pathogenic gene variants, and thus have increased risk of developing gastric or other cancers. Ideally, germline pathogenic variants can be identified in family members before the onset of disease, when early detection or prevention strategies can be implemented most effectively to decrease gastric cancer- related morbidity and mortality. This article reviews some of the currently known gastric cancer predisposition syndromes and their associated cancer risks. We also discuss current research and advances in the field of genetic gastric cancer susceptibility.
    Language English
    Publishing date 2019-07-29
    Publishing country China
    Document type Journal Article ; Review
    ISSN 2415-1289
    ISSN (online) 2415-1289
    DOI 10.21037/tgh.2019.07.02
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  10. Article ; Online: Bilateral Oophorectomy and All-Cause Mortality in Women With BRCA1 and BRCA2 Sequence Variations.

    Kotsopoulos, Joanne / Gronwald, Jacek / Huzarski, Tomasz / Møller, Pål / Pal, Tuya / McCuaig, Jeanna M / Singer, Christian F / Karlan, Beth Y / Aeilts, Amber / Eng, Charis / Eisen, Andrea / Bordeleau, Louise / Foulkes, William D / Tung, Nadine / Couch, Fergus J / Fruscio, Robert / Neuhausen, Susan L / Zakalik, Dana / Cybulski, Cezary /
    Metcalfe, Kelly / Olopade, Olufunmilayo I / Sun, Ping / Lubinski, Jan / Narod, Steven A

    JAMA oncology

    2024  Volume 10, Issue 4, Page(s) 484–492

    Abstract: Importance: Preventive bilateral salpingo-oophorectomy is offered to women at high risk of ovarian cancer who carry a pathogenic variant in BRCA1 or BRCA2; however, the association of oophorectomy with all-cause mortality has not been clearly defined.!## ...

    Abstract Importance: Preventive bilateral salpingo-oophorectomy is offered to women at high risk of ovarian cancer who carry a pathogenic variant in BRCA1 or BRCA2; however, the association of oophorectomy with all-cause mortality has not been clearly defined.
    Objective: To evaluate the association between bilateral oophorectomy and all-cause mortality among women with a BRCA1 or BRCA2 sequence variation.
    Design, setting, and participants: In this international, longitudinal cohort study of women with BRCA sequence variations, information on bilateral oophorectomy was obtained via biennial questionnaire. Participants were women with a BRCA1 or BRCA2 sequence variation, no prior history of cancer, and at least 1 follow-up questionnaire completed. Women were followed up from age 35 to 75 years for incident cancers and deaths. Cox proportional hazards regression was used to estimate the hazard ratios (HRs) and 95% CIs for all-cause mortality associated with a bilateral oophorectomy (time dependent). Data analysis was performed from January 1 to June 1, 2023.
    Exposures: Self-reported bilateral oophorectomy (with or without salpingectomy).
    Main outcomes and measures: All-cause mortality, breast cancer-specific mortality, and ovarian cancer-specific mortality.
    Results: There were 4332 women (mean age, 42.6 years) enrolled in the cohort, of whom 2932 (67.8%) chose to undergo a preventive oophorectomy at a mean (range) age of 45.4 (23.0-77.0) years. After a mean follow-up of 9.0 years, 851 women had developed cancer and 228 had died; 57 died of ovarian or fallopian tube cancer, 58 died of breast cancer, 16 died of peritoneal cancer, and 97 died of other causes. The age-adjusted HR for all-cause mortality associated with oophorectomy was 0.32 (95% CI, 0.24-0.42; P < .001). The age-adjusted HR was 0.28 (95% CI, 0.20-0.38; P < .001) and 0.43 (95% CI, 0.22-0.90; P = .03) for women with BRCA1 and BRCA2 sequence variations, respectively. For women with BRCA1 sequence variations, the estimated cumulative all-cause mortality to age 75 years for women who had an oophorectomy at age 35 years was 25%, compared to 62% for women who did not have an oophorectomy. For women with BRCA2 sequence variations, the estimated cumulative all-cause mortality to age 75 years was 14% for women who had an oophorectomy at age 35 years compared to 28% for women who did not have an oophorectomy.
    Conclusions and relevance: In this cohort study among women with a BRCA1 or BRCA2 sequence variation, oophorectomy was associated with a significant reduction in all-cause mortality.
    MeSH term(s) Female ; Humans ; Adult ; Middle Aged ; Aged ; Male ; BRCA1 Protein/genetics ; BRCA2 Protein/genetics ; Cohort Studies ; Longitudinal Studies ; Mutation ; Ovariectomy ; Breast Neoplasms/mortality ; Risk Management ; Ovarian Neoplasms/pathology
    Chemical Substances BRCA1 protein, human ; BRCA1 Protein ; BRCA2 protein, human ; BRCA2 Protein
    Language English
    Publishing date 2024-02-29
    Publishing country United States
    Document type Journal Article ; Comment
    ISSN 2374-2445
    ISSN (online) 2374-2445
    DOI 10.1001/jamaoncol.2023.6937
    Database MEDical Literature Analysis and Retrieval System OnLINE

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