Women’s Health Initiative (WHI) - Life and Longevity After Cancer (LILAC)(WHI-LILAC-BioLINCC)
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PROVIDER: PRJNA1291287 | ENA |
REPOSITORIES: ENA
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Project description:Women’s Health Initiative (WHI) - Life and Longevity After Cancer (LILAC)(WHI-LILAC-BioLINCC)
| PRJNA1291286 | ENA
Project description:Estrogen is thought to cause proliferation of all estrogen receptor positive (ER+) breast cancers. Paradoxically, in the Women’s Health Initiative Trial, estrogen-only hormone replacement therapy reduced the incidence and mortality of low grade, ER+, HER2- breast cancer. We gave estradiol to 19 post-menopausal women with newly diagnosed low-grade, ER+, HER2- breast cancer in a prospective window of opportunity clinical trial and examined the changes in proliferation and gene expression before and after estradiol treatment. Ki67 decreased in 13/19 (68%) patients and 8/13 (62%) showed a decrease in Risk of Recurrence Score. We chose three prototypical estrogen responders (greatest decrease in ROR) and non-responders (no/minimal change in ROR) and applied a differential gene expression analysis to develop pre-treatment (PRESTO-30core) and post-treatment (PRESTO-45surg) gene expression profiles. The PRESTO-30core predicted adjuvant benefit in a published series of tamoxifen, the partial estrogen agonist. Of the 45 genes in the PRESTO-45surg, thirty contain the Cell cycle genes Homology Region (CHR) motif that binds the class B multi-vulva complex (MuvB) a member of the DREAM (Dimerization partner, retinoblastoma-like proteins, E2F, MuvB) complex responsible for reversible cell cycle arrest or quiescence. There was also near uniform suppression (89%) of the remaining DREAM genes consistent with estrogen induced activation of the DREAM complex to mediate cell cycle block after a short course of estrogens. To our knowledge, this is the first report to show hormonal modulation of DREAM genes and suggest involvement of DREAM pathway associated quiescence in endocrine responsive post-menopausal ER+ breast cancers.
2021-12-27 | GSE139688 | GEO
Project description:Background: The Women's Health Initiative (WHI) Life and Longevity After Cancer (LILAC) study offers an important opportunity to advance cancer research by extending the original WHI studies to examine survivorship in women diagnosed with cancer during their participation in WHI.Methods: The goals of LILAC are to (i) obtain cancer treatment information and long-term cancer outcomes for women diagnosed with one of eight selected cancers (breast, endometrial, ovarian, lung, and colorectal cancers, and melanoma, lymphoma, and leukemia); (ii) augment the existing WHI biorepository with fixed tumor tissue from the solid tumor sites for cancers diagnosed since 2002; and (iii) develop, refine, and validate methods to use administrative data to capture treatment and recurrence data. Methods for accomplishing these goals are described, as are results from the initial LILAC participant survey.Results: A total of 9,934 WHI participants living with cancer were eligible for LILAC participation, of which 78% (N = 7,760) agreed to participate. Among the three most prevalent cancer types, 54% are breast cancer survivors, 11% are melanoma survivors, and 10% are survivors of colorectal cancer.Conclusions: In addition to describing this resource, we present pertinent lessons that may assist other investigators interested in embedding survivorship research into existing large epidemiologic cohorts.Impact: The LILAC resource offers a valuable opportunity for researchers to study cancer survivorship and issues pertinent to cancer survivors in future studies. Cancer Epidemiol Biomarkers Prev; 27(2); 125-37. ©2017 AACR.
| S-EPMC5809310 | biostudies-literature
Project description:Center for Common Disease Genomics [CCDG] - Cardiovascular: Women's Health Initiative (WHI) Cohort
| PRJNA955371 | ENA
Project description:Center for Common Disease Genomics [CCDG] - Cardiovascular: Women's Health Initiative (WHI) Cohort
| PRJNA955372 | ENA
Project description:DREAM, a Possible Answer to the Estrogen Paradox of the Women’s Health Initiative Trial
| PRJNA586892 | ENA
Project description:<p>This is Whole Genome Sequencing data from the TOPMed participation of the Women's Health Initiative. Approximately 11,100 subjects were involved in this study: approximately 1,100 cases of VTE, 4,000 cases of ischemic stroke, 900 cases of hemorrhagic stroke, and 5,100 controls. Summary level phenotypes for the WHI Cohort study participants can be viewed at the top-level study page phs000200 WHI Cohort. Individual level phenotype data and molecular data for all WHI top-level study and substudies are available by requesting Authorized Access to the WHI Cohort study <a href="./study.cgi?study_id=phs000200">phs000200</a>.</p>
| phs001237 | dbGaP
Project description:WHI Long Life Study Phase III GWAS Data
| PRJNA474346 | ENA
Project description:Despite extensive studies at the genomic, transcriptomic and metabolomic levels, the underlying mechanisms regulating longevity are incompletely understood. Post-translational protein acetylation is suggested to regulate aspects of longevity. To further explore the role of acetylation, we develop the PHARAOH computational tool based on the 100-fold differences in longevity within the mammalian class. Analyzing acetylome and proteome data across 107 mammalian species identifies 482 and 695 significant longevity-associated acetylated lysine residues in mice and humans, respectively. These sites include acetylated lysines in short-lived mammals that are replaced by permanent acetylation or deacetylation mimickers, glutamine or arginine, respectively, in long-lived mammals. Conversely, glutamine or arginine residues in short-lived mammals are replaced by reversibly acetylated lysine in long-lived mammals. Pathway analyses highlight the involvement of mitochondrial translation, cell cycle, fatty acid oxidation, transsulfuration, DNA repair and others in longevity. A validation assay shows that substituting lysine 386 with arginine in mouse cystathionine beta synthase, to attain the human sequence, increases the pro-longevity activity of this enzyme. Likewise, replacing the human ubiquitin-specific peptidase 10 acetylated lysine 714 with arginine as in short-lived mammals, reduces its anti-neoplastic function. Overall, in this work we propose a link between the conservation of protein acetylation and mammalian longevity.
2025-03-30 | PXD061654 | Pride