Comparison of the roles of estrogens and androgens in breast cancer and prostate cancer

Liu, Wenjing; Zhao, Gang; Zhang, Chenyan; Chen, Yang; Zeng, Xianyi; Li, Jin; Zhu, Kun; Song, Zhao; Lu, Hui‐Meng; Yin, Da‐Chuan; Lin, Szu-Yuan

doi:10.1002/jcb.29515

Cited by 16 publications

(12 citation statements)

References 121 publications

(275 reference statements)

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“…Combining these ndings with previous studies suggesting dual effects of estrogen on PRAD (inhibition at high serum estrogen concentrations and promotion at lower concentrations) contributes to a comprehensive understanding of the impact of oral contraceptive drugs and sex hormones on cancer risk [73].…”

Section: Effects Of Lipid-lowering Oral Contraceptive Hormones and In...supporting

confidence: 57%

Genetically predicted causal associations between 152 blood-related exposures and pan-cancer in the framework of prediction, prevention and personalized medicine: a study integrating Mendelian randomization and bioinformatics

tang,

tian,

et al. 2024

Preprint

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Objective Blood serves as a powerful tool for monitoring the intricate landscape of cancer development. Previous studies have emerged, suggesting that hematologic indicators hold promise in predicting the onset of malignancy. This present investigation aims to delve into the underlying causal connections between blood-related indicators and pan-cancer, further elucidating the potential impact of diseases and medication utilization reflected in these indicators on cancer, within the realm of predictive, preventive and personalised medicine(PPPM). Methods To embark on this scientific endeavor, we procured summary-level data from a genome-wide association studies (GWAS) encompassing blood-related indicators and cis-eQTLs of drug target genes, from the esteemed IEU OpenGWAS. Additionally, we obtained GWAS summary-level data encapsulating pan-cancer (consisting of an impressive cohort of 659,582 cases and 12,186,911 controls), along with diseases annotated by their correlation to blood-related indicators, from esteemed sources such as IEU OpenGWAS, UK Biobank, FinnGen, and Biobank Japan. In order to unravel the direct causal associations between blood-related indicators and pan-cancer, as well as the causal implications between the diseases manifested by these indicators and cancer, we initiated a robust analysis employing the two-sample Mendelian randomization(MR) method. Furthermore, utilizing bioinformatics methodologies, we went on to explore the potential effects of drug target genes on pan-cancer. Results Preliminary findings from our MR analysis provided compelling evidence of a significant link between blood-related exposures and pan-cancer. Drawing upon the intriguing interplay observed between blood pressure and tumors, it was postulated that monitoring hypertension (HTN) may offer notable advantages in the prevention of colorectal adenocarcinoma (COAD), breast carcinoma (BRCA), and esophageal carcinoma (ESCA). Similarly, considering the captivating relationship between blood glucose, insulin levels, and tumors, it was hypothesized that closely monitoring diabetes mellitus (DM) could prove beneficial in the prevention of stomach adenocarcinoma (STAD) and COAD. In consonance with the intriguing connection discovered between red blood cell counts, distribution width, and tumors, our findings supported the notion that monitoring anemia could impart advantageous effects in the prevention of lung adenocarcinoma (LUAD). Remarkably, drawing upon the intriguing relationship observed between deep vein thrombosis (DVT) and tumors, it was hypothesized that surveillance of DVT might prove valuable in the prevention of COAD. Additionally, we noted a disparity in risk for various cancers, including lung, breast, colorectal, ovarian, prostate, and pancreatic, consequent to the utilization of drugs for these aforementioned diseases. Among our identified drug targets, we carefully sifted through and diligently analyzed three pivotal genes, namely HMGCR, INSR, and NR3C1, fostering the prospect of formulating novel, tumor-targeted therapeutics. However, our investigation yielded insufficient evidence to confirm any mediating effects of glycated hemoglobin (HbA1c), hemoglobin-gastric, D-dimer, and renin on the associations between HTN, anemia, DVT, DM, and pan-cancer. Conclusions The present study unveils the intricate web of causal associations between blood-related indicators, the diseases they manifest, and medication utilization, all of which significantly impact the development of cancer. Notably, the potential for utilizing blood-related indicators as pioneering biomarkers for cancer prediction and prevention is underscored, showcasing a remarkable avenue for advancing PPPM strategies in the field of oncology. This seminal investigation serves as a beacon of novel insight, engendering the construction of refined and tailored approaches to combat the formidable challenge of cancer.

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Section: Effects Of Lipid-lowering Oral Contraceptive Hormones and In...supporting

confidence: 57%

Genetically predicted causal associations between 152 blood-related exposures and pan-cancer in the framework of prediction, prevention and personalized medicine: a study integrating Mendelian randomization and bioinformatics

tang,

tian,

et al. 2024

Preprint

View full text Add to dashboard Cite

show abstract

“…Additionally, hormone signaling is dysregulated in several cancers, such as breast and prostate cancer, and contributes to promoting tumorigenesis [258,265]. Thus, combined hormonal therapies with HDACis are promising strategies for the treatment of hormonedependent cancers.…”

Section: Combined Clinical Strategies With Histone Deacetylases Inhib...mentioning

confidence: 99%

Targeting Histone Deacetylases: Opportunities for Cancer Treatment and Chemoprevention

et al. 2022

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The dysregulation of gene expression is a critical event involved in all steps of tumorigenesis. Aberrant histone and non-histone acetylation modifications of gene expression due to the abnormal activation of histone deacetylases (HDAC) have been reported in hematologic and solid types of cancer. In this sense, the cancer-associated epigenetic alterations are promising targets for anticancer therapy and chemoprevention. HDAC inhibitors (HDACi) induce histone hyperacetylation within target proteins, altering cell cycle and proliferation, cell differentiation, and the regulation of cell death programs. Over the last three decades, an increasing number of synthetic and naturally derived compounds, such as dietary-derived products, have been demonstrated to act as HDACi and have provided biological and molecular insights with regard to the role of HDAC in cancer. The first part of this review is focused on the biological roles of the Zinc-dependent HDAC family in malignant diseases. Accordingly, the small-molecules and natural products such as HDACi are described in terms of cancer therapy and chemoprevention. Furthermore, structural considerations are included to improve the HDACi selectivity and combinatory potential with other specific targeting agents in bifunctional inhibitors and proteolysis targeting chimeras. Additionally, clinical trials that combine HDACi with current therapies are discussed, which may open new avenues in terms of the feasibility of HDACi’s future clinical applications in precision cancer therapies.

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“…For example, in men, the primary sex hormones are androgens, which typically associate with male traits developing during puberty. However, sex hormones have also been associated with an increased risk of some types of cancer, including breast and prostate cancer [ 1 ]. These cancers are highly dependent on sex hormones for cell proliferation, and hormone suppression is, therefore, an effective therapeutic tool.…”

Section: Introductionmentioning

confidence: 99%

An epigenome-wide analysis of sex hormone levels and DNA methylation in male blood samples

et al. 2023

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Endogenous sex hormones and DNA methylation both play important roles in various diseases. However, their interplay is largely unknown. A deeper understanding of their interrelationships could provide new insights into the pathology of disease development. We, therefore, investigated associations between circulating sex hormones, sex hormone binding globulin (SHBG), and DNA methylation in blood, using samples from 77 men (65 with repeated samples), from the population-based Northern Sweden Health and Disease Study (NSHDS). DNA methylation was measured in buffy coat using the Infinium Methylation EPIC BeadChip (Illumina). Sex hormone (oestradiol, oestrone, testosterone, androstenedione, dehydroepiandrosterone, and progesterone) and SHBG concentrations were measured in plasma using a high-performance liquid chromatography tandem mass spectrometry (LC/MS-MS) method and an enzyme-linked immunoassay, respectively. Associations between sex hormones, SHBG, and DNA methylation were estimated using both linear regression and mixed-effects models. Additionally, we used the comb-p method to identify differentially methylated regions based on nearby P values. We identified one novel CpG site (cg14319657), at which DNA methylation was associated with dehydroepiandrosterone, surpassing a genome-wide significance level. In addition, more than 40 differentially methylated regions were associated with levels of sex hormones and SHBG and several of these mapped to genes involved in hormone-related diseases. Our findings support a relationship between circulating sex hormones and DNA methylation and suggest that further investigation is warranted, both for validation, further exploration and to gain a deeper understanding of the mechanisms and potential consequences for health and disease.

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Comparison of the roles of estrogens and androgens in breast cancer and prostate cancer

Cited by 16 publications

References 121 publications

Genetically predicted causal associations between 152 blood-related exposures and pan-cancer in the framework of prediction, prevention and personalized medicine: a study integrating Mendelian randomization and bioinformatics

Genetically predicted causal associations between 152 blood-related exposures and pan-cancer in the framework of prediction, prevention and personalized medicine: a study integrating Mendelian randomization and bioinformatics

Targeting Histone Deacetylases: Opportunities for Cancer Treatment and Chemoprevention

An epigenome-wide analysis of sex hormone levels and DNA methylation in male blood samples

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