Cancer Mortality In Men Research Articles

Anemia, Iron Deficiency, and Cause-Specific Mortality: The Atherosclerosis Risk in Communities Study

Introduction: Anemia is a risk factor for all-cause mortality in older adults. Iron deficiency may also be associated with adverse outcomes, independent of its role in causing anemia. This study tested the hypotheses that anemia, and low ferritin among non-anemic participants, were associated with all-cause and cause-specific mortality in a community-based cohort of older adults. Methods: Fasting blood was obtained from 5,070 ARIC participants (median age: 75 years) in 2011–2013. Anemia was defined by hemoglobin concentrations <12 g/dL in women and <13 g/dL in men. We classified 4,020 non-anemic participants by quartiles of plasma ferritin, measured by the SomaScan proteomics platform. Cox proportional hazards regression was used. Mortality was ascertained via phone calls with proxies as part of twice-yearly cohort follow-up, surveillance of local hospital discharge indexes, state death records, and linkage to the National Death Index. Results: Of the total participants, 21% had anemia at baseline. Over a median of 7.5 years, there were 1,147 deaths, including 357 due to cardiovascular disease (CVD), 302 to cancer, and 132 to respiratory disease. Compared to those with normal hemoglobin, participants with anemia had a higher risk of all-cause mortality (hazard ratio 1.81 [95% CI: 1.60–2.06]), and mortality due to CVD (1.77 [1.41–2.22]), cancer (1.81 [1.41–2.33]), and respiratory disease (1.72 [1.18–2.52]) in demographics-adjusted models. In fully adjusted models, associations with all-cause mortality (1.37 [1.19–1.58]) and cause-specific mortality were attenuated. In non-anemic participants, lower ferritin levels were not associated with all-cause or cause-specific mortality, though associations were observed among participants with lesser evidence of inflammation (CRP below the median level of 1.9 mg/L) and for cancer mortality in men only. Conclusion: Anemia is common among older adults and is associated with all-cause mortality, as well as mortality due to CVD, cancer, and respiratory disease. Our results do not provide evidence that iron deficiency, independent of anemia, is associated with mortality in this population.

Predictors of long-term prostate cancer mortality in men continuing prostate-specific antigen screening after age 70.

Predictors of long-term prostate cancer mortality in men continuing prostate-specific antigen screening after age 70.

Pluvicto in the real world setting and timing to PSA50 as a predictive marker of treatment response.

e17026 Background: Prostate cancer, the leading cause of cancer mortality in men, has seen notable advances with PSMA-targeted therapies like 177Lu-PSMA-617 (Pluvicto), particularly in the metastatic castrate resistant setting. While prostate specific antigen (PSA) serves as a useful biomarker in newly diagnosed patients or those on androgen deprivation therapy, its efficacy in monitoring patients under PSMA-directed therapy remains unclear. This underscores a critical gap: the absence of established biomarkers for tracking response to these emerging treatments. Such biomarkers are vital for enhancing patient outcomes and evaluating therapeutic efficacy in early-stage trials. Methods: In this real-world, cohort study, we retrospectively followed adult patients with metastatic, castrate-resistant prostate cancer who are treated with Pluvicto at our institution beginning January 1, 2022 through November 2023. We assessed several potential biomarkers of response temporally throughout the treatment duration of Pluvicto, including serial blood counts, chemistry profiles, PSA levels, BMI, as well as their historical treatment patterns and demographics. All patients were heavily pre-treated prior to receiving Pluvicto. By using logistic regression, we identify factors associated with treatment response. Results: In our study, 21 patients qualified for enrolment. These patients received a median of 6 treatments prior to Pluvicto. Among them, 8 (38.1%) demonstrated at least PSA50 and showed response post-treatment. Of these, 6 (75%) completed all six Pluvicto treatments, while 2 (25%) are currently undergoing treatment. Remarkably, 7 of the 8 responders (87.5%) achieved a PSA50 response after two Pluvicto doses, with all 8 (100%) reaching this marker by the third dose. Furthermore, 6 of these 8 patients (75%) exhibited a PSA90 response after the fourth dose, though 2 patients (25%) did not attain PSA90. Conclusions: Our real-world study at Scripps Clinic provides valuable insights into the efficacy of Pluvicto in treating metastatic, castrate-resistant prostate cancer. Out of 21 patients treated with Pluvicto, 38.1% exhibited a significant PSA decrease during the treatment course. Notably, 87.5% of responders achieved PSA50 before their third dose, and all responders reached this benchmark prior to their fourth dose. These findings are crucial, especially as clinical trials are exploring Pluvicto's application in earlier treatment stages. Additionally, the use of PSA50 as a biomarker could guide clinicians in timely decision-making, allowing for quicker intervention and therapy adjustments, thus potentially mitigating disease progression. Updated data to be presented.

Plant-based dietary patterns and mortality from all causes, cardiovascular disease, and cancer: The Multiethnic Cohort Study

Background and aimsPlant-based dietary patterns have been associated with lower risk of cardiovascular disease (CVD), some cancers, and related mortality in U.S. populations. However, the quality of plant foods has rarely been considered in the association between plant-based diets and mortality, especially in a population with various racial and ethnic backgrounds. We investigated whether the adherence to plant-based dietary patterns and the healthiness of plant foods are associated with mortality from all causes, CVD, and cancer and evaluated how the association varies by race and ethnicity MethodsA total of 144,729 African American, Japanese American, Latino, Native Hawaiian, and White men and women who participated in the Multiethnic Cohort Study (1993-2019) were included. Cox models were used to estimate HR and 95% CI of mortality from all causes, CVD, and cancer across quintiles of three plant-based diet scores: overall plant-based diet index (PDI), healthful plant-based diet index (hPDI), and unhealthful plant-based diet index (uPDI). ResultsOver an average 21 years of follow-up, we identified 65,087 deaths, including 18,663 from CVD and 16,171 from cancer. Comparing the highest versus lowest quintiles, greater scores of PDI and hPDI were associated with a lower risk of all-cause mortality in both men (HR=0.85, 95% CI: 0.82-0.89 for PDI; HR=0.88, 95% CI: 0.85-0.91 for hPDI; both P for trend <0.0001) and women (HR=0.89, 95% CI: 0.86-0.93 for PDI; HR=0.86, 95% CI: 0.83-0.89 for hPDI; both P for trend <0.0001). An increased risk of all-cause mortality with uPDI was observed only in women (HR=1.11, 95% CI: 1.07-1.15, P for trend <0.0001; P for heterogeneity by sex =0.019). A similar trend was shown for CVD mortality with a significant increase in risk with uPDI for both men and women. PDI was associated with a lower risk of cancer mortality in men (HR=0.86, 95% CI: 0.80-0.92, P for trend <0.0001), while neither hPDI nor uPDI was associated in either sex. Compared with the other racial and ethnic groups within each sex, the association of uPDI with all-cause mortality was stronger in White men (P for heterogeneity by race and ethnicity = 0.009) and weaker in Latino women (P for heterogeneity = 0.002). ConclusionA healthy plant-based dietary pattern emphasizing the quality of plant foods was associated with a lower risk of all-cause and CVD mortality in both men and women, although the magnitude of the associations varied across racial and ethnic groups.

Abstract 2234: Cardiovascular disease risk among men with prostate cancer: Differences by prostate cancer aggressiveness

Abstract Background: Cardiovascular disease (CVD) is a major cause of morbidity and mortality among men diagnosed with prostate cancer. We evaluated the extent to which men with prostate cancer develop CVD accounting for potential factors that may contribute to the CVD burden in this population. Methods: We prospectively followed men diagnosed with prostate cancer and free from CVD (stroke and coronary heart disease, including myocardial infarction, coronary artery bypass graft, and percutaneous coronary intervention) before their cancer diagnosis in the Health Professionals Follow-up Study, between 1986 and 2016. Men were categorized by D’Amico prostate cancer risk groups as low-risk (stage T1-2a, Gleason score ≤6, and PSA at diagnosis ≤10 ng/mL), intermediate-risk (T2b and/or Gleason score 7 and/or PSA &amp;gt;10-20), or high-risk (≥T2c/N1/M1 or Gleason score 8-10 or PSA &amp;gt;20). Incident fatal and non-fatal CVD, defined as coronary heart disease and stroke after cancer diagnosis, were centrally adjudicated. CVD risk factors including smoking, hyperlipidemia, hypertension, diabetes mellitus, body mass index, were self-reported on biennial questionnaires. Deaths due to prostate cancer or other causes were treated as competing events when estimating cumulative incidence and cause-specific hazard ratios (HR). Results: Among 5,707 prostate cancer patients, 1,912 had low-risk, 2,261 had intermediate-risk, and 1,534 had high-risk cancer. 1,102 CVD events were documented over up to 30 years of follow-up after cancer diagnosis. The 10-year CVD risk was 8.1% for men with low-risk cancer, 8.8% for intermediate-risk, and 10.4% for high-risk cancer. The cause-specific HRs for CVD were 1.18 (95% CI 1.03, 1.36) in intermediate-risk and 1.59 (95% CI 1.36, 1.85) in high-risk prostate cancer, both compared to low-risk prostate cancer. Men with high-risk cancer tended to be older; after age adjustment, the HRs were 1.15 for intermediate-risk (95% CI 1.00, 1.33) and 1.35 for high-risk cancer (1.35, 95% CI 1.16, 1.58). Associations between cancer risk group and CVD were essentially unchanged after further adjustment for CVD risk factors present at cancer diagnosis, primary cancer treatment modality (surgery, radiation, androgen deprivation therapy, watchful waiting/active surveillance), and calendar year of diagnosis. Discussion: Despite the elevated risk of cancer mortality in men with intermediate-risk and high-risk prostate cancer compared to low-risk prostate cancer, CVD risk remains at least as common over time among these men as among men with low-risk prostate cancer. Incident CVD risk after cancer diagnosis among men with more aggressive cancers, which particularly occur in older men, is not primarily attributable to differences in pre-existing risk factor burden. These findings from a cohort with healthcare access and literacy indicate a need for continued clinical attention to CVD after cancer diagnosis. Citation Format: Caroline Himbert, Anna Plym, Jane B. Vaselkiv, Andreas Pettersson, Philip W. Kantoff, Lorelei A. Mucci, Kenneth J. Mukamal, Konrad H. Stosapck. Cardiovascular disease risk among men with prostate cancer: Differences by prostate cancer aggressiveness [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 2234.

Abstract 7200: Non-cytotoxic inhibition of nuclear encoded mitochondrial protein MAGMAS resensitize treatment resistant prostate cancer cells to taxane therapy

Abstract Metastatic prostate cancer (PCa) is the leading cause of PCa-associated deaths and one of the leading causes of cancer mortality in men. Novel therapeutics, such as Prostate Specific Membrane Antigen (PSMA) ligand therapy, are emerging as effective treatment strategies for metastatic prostate cancer. However, most men succumb to Metastatic Castration Resistant Prostate Cancer (mCRPC) due to treatment resistance. MAGMAS, a 13.8 kDa mitochondrial protein, imports nuclear-encoded mitochondrial proteins into the mitochondrial matrix. MAGMAS is overexpressed in several aggressive tumors, such as breast cancer, glioblastoma, and prostate cancer. When overexpressed, MAGMAS plays a role as a cytoprotective protein by acting as a reactive oxygen species (ROS) scavenger that maintains sufficient ROS levels to promote cell proliferation but below the threshold levels that could lead to apoptosis. This study was designed to investigate the pro-survival and therapy-resistance functions of MAGMAS in treatment-resistant PCa cells. Predictively, we observed that the docetaxel (DTX)-resistant PC3-DR and DU145-DR PCa cell lines expressed significantly higher levels of MAGMAS compared to their drug-sensitive parental cell lines. We hypothesized that inhibiting Magmas reduces the aggressive properties of highly proliferative DTX-resistant metastatic PCa cell lines and re-sensitizes them to DTX. MAGMAS knockdown in DTX-resistant PC3 and DU145 cells in the presence of increasing DTX treatments enhanced sensitivity to DTX. Consistent with these results, pharmacological inhibition of MAGMAS with the novel BT#9 inhibitor in combination with increasing DTX concentrations also enhanced sensitivity to DTX in these cell lines. Additional studies using cell migration/invasion assays and tumor-sphere formation assays are underway to further establish MAGMAS as a potential therapeutic target to attenuate the aggressive properties of chemo-resistant PCa cells. Lastly, we will investigate the diagnostic potential of MAGMAS as a biomarker for advanced PCa and BT#9 as an imaging/therapeutic-specific agent for treatment-resistant tumors. Citation Format: Alfonso Duran, Kristen Whitley, Krystal Santiago, Adil Mohammed, Carlos Casiano, Bhaskar Das, Frankis Almaguel. Non-cytotoxic inhibition of nuclear encoded mitochondrial protein MAGMAS resensitize treatment resistant prostate cancer cells to taxane therapy [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 7200.

Cancer mortality in chrysotile miners and millers, Russian Federation: main results (Asbest Chrysotile Cohort-Study)

Background. We investigated mortality in workers of the world’s largest chrysotile mine and enrichment factories located in the town of Asbest, Russian Federation.&#x0D; Methods. This historical cohort study included all workers employed for at least 1 year between 1975 and 2010 and follow-up until the end of 2015. Cumulative exposure to dust was estimated based on workers’ complete occupational history linked to dust measurements systematically collected from the 1950s. Exposure to chrysotile fibers was estimated using dust-to-fiber conversion factors. Relative risks (RRs) and 95% confidence intervals (CIs) were estimated as mortality rate ratios in Poisson regression models.&#x0D; Results. A total of 30 445 (32% women) workers accumulated 721 312 person-years at risk and 11 110 (36%) died. Of the workers, 54% had more than 30 years since their first exposure. We found an exposure-response between cumulative dust and lung cancer mortality in men. No clear association with dust exposure but a modest increase in the highest category of fiber exposure was seen for lung cancer in women. Mesothelioma mortality was increased (RR=7.64, 95% CI=1.18 to 49.5, to at least 80 fibers per cm3 years and RR=4.56, 95% CI=0.94 to 22.1, to at least 150 mg/m3 years [dust]), based on 13 deaths. For colorectal and stomach cancer, there were inconsistent associations. No associations were seen for laryngeal or ovarian cancer.&#x0D; Conclusion. In this large-scale epidemiological study in the world’s largest active asbestos mine, we confirmed an increased risk of mesothelioma with high fiber exposure and an increasing mortality for lung cancer in men with increasing dust exposure. Less clear-cut increased lung cancer mortality was seen in the women. Continued mortality follow-up is warranted.

Cancer mortality in chrysotile miners and millers, Russian Federation: main results (Asbest Chrysotile Cohort-Study).

We investigated mortality in workers of the world's largest chrysotile mine and enrichment factories located in the town of Asbest, Russian Federation. This historical cohort study included all workers employed for at least 1 year between 1975 and 2010 and follow-up until the end of 2015. Cumulative exposure to dust was estimated based on workers' complete occupational history linked to dust measurements systematically collected from the 1950s. Exposure to chrysotile fibers was estimated using dust-to-fiber conversion factors. Relative risks (RRs) and 95% confidence intervals (CIs) were estimated as mortality rate ratios in Poisson regression models. A total of 30 445 (32% women) workers accumulated 721 312 person-years at risk and 11 110 (36%) died. Of the workers, 54% had more than 30 years since their first exposure. We found an exposure-response between cumulative dust and lung cancer mortality in men. No clear association with dust exposure but a modest increase in the highest category of fiber exposure was seen for lung cancer in women. Mesothelioma mortality was increased (RR = 7.64, 95% CI = 1.18 to 49.5, to at least 80 fibers per cm3 years and RR = 4.56, 95% CI = 0.94 to 22.1, to at least 150 mg/m3 years [dust]), based on 13 deaths. For colorectal and stomach cancer, there were inconsistent associations. No associations were seen for laryngeal or ovarian cancer. In this large-scale epidemiological study in the world's largest active asbestos mine, we confirmed an increased risk of mesothelioma with high fiber exposure and an increasing mortality for lung cancer in men with increasing dust exposure. Less clear-cut increased lung cancer mortality was seen in the women. Continued mortality follow-up is warranted.

Organoids: An Emerging Precision Medicine Model for Prostate Cancer Research.

Prostate cancer (PCa) has been known as the most prevalent cancer disease and the second leading cause of cancer mortality in men almost all over the globe. There is an urgent need for establishment of PCa models that can recapitulate the progress of genomic landscapes and molecular alterations during development and progression of this disease. Notably, several organoid models have been developed for assessing the complex interaction between PCa and its surrounding microenvironment. In recent years, PCa organoids have been emerged as powerful in vitro 3D model systems that recapitulate the molecular features (such as genomic/epigenomic changes and tumor microenvironment) of PCa metastatic tumors. In addition, application of organoid technology in mechanistic studies (i.e., for understanding cellular/subcellular and molecular alterations) and translational medicine has been recognized as a promising approach for facilitating the development of potential biomarkers and novel therapeutic strategies. In this review, we summarize the application of PCa organoids in the high-throughput screening and establishment of relevant xenografts for developing novel therapeutics for metastatic, castration resistant, and neuroendocrine PCa. These organoid-based studies are expected to expand our knowledge from basic research to clinical applications for PCa diseases. Furthermore, we also highlight the optimization of PCa cultures and establishment of promising 3D organoid models for in vitro and in vivo investigations, ultimately facilitating mechanistic studies and development of novel clinical diagnosis/prognosis and therapies for PCa.

Advancing early onset colorectal cancer research: research advocacy, health disparities, and scientific imperatives.

Early onset colorectal cancer (EOCRC) emerged as the fourth foremost contributor to cancer-related mortality among both genders in the late 1990s. Presently, EOCRC (<50) ranks as the leading cause of cancer mortality in men and the second leading cause in women within the United States. Similar trends are now also evident globally, particularly in developed countries. Furthermore, there is strong evidence confirming that health disparities persist in the diagnosis and treatment of EOCRC, with signs indicating that these gaps may worsen in specific cases. These alarming trends highlight the critical need for research to inform evidence-based interventions to reduce the burden of EOCRC globally. Fight Colorectal Cancer (Fight CRC) is the leading patient advocacy group in the United States providing information on colon and rectal cancer research, prevention, treatment, and policy. It is the opinion of Fight CRC that an international, coordinated effort with the medical, research, scientific, advocacy, industry and funding community is needed to advance impactful research. Fight CRC, in partnership with José Perea, MD, PhD, of the Institute of Biomedical Research of Salamanca (IBSAL) in Spain, and partners, are working together to address this global phenomenon and are presenting a multi-faceted research approach to move the field forward.

2023 Update On the Screening and Treatment of Localized Prostate Cancer

Prostate cancer represents a major burden of disease in Canada. It represents the third leading cause of cancer mortality in men with more than 24,000 individuals diagnosed in 2021. The diagnosis and management of prostate cancer is a continuously evolving area, and the aim of this article is to provide current information on various aspects of prostate cancer care, as an aid for primary care physicians (PCPs) as they guide men through the prostate cancer journey.

OC 51.4 Low Thrombin Inactivation Capacity is an Independent Risk Factor for Cancer Mortality in Men: Results from the Moli-Sani Study

OC 51.4 Low Thrombin Inactivation Capacity is an Independent Risk Factor for Cancer Mortality in Men: Results from the Moli-Sani Study

Prostate Cancer Detection through MR Images based on Black Hole Optimization Algorithm

Introduction: Prostate cancer is the most common type of malignant cancer among men and is known as one of the leading causes of cancer mortality in men. The complexity of diagnostic procedures such as mass biopsy has made new diagnostic strategies for prostate cancer, such as MRI imaging, a research priority in recent years. Methods: In this applied-descriptive study, a four steps method for diagnosing prostate cancer through MR image is presented. In the first step, the destructive effect of noise on the input images by using two-dimensional wavelet transform and histogram equalization is reduced. In the second step, the black hole optimization algorithm is used for segmentation of the input image based on the multilevel threshold technique. By doing this, the suspicious areas are identified in the image and in the third step, the features of each target area are extracted. In the fourth step, a combination of three learning algorithms, including: artificial neural network, decision and support vector machine is used to diagnose prostate cancer. Results: The effectiveness of the proposed method in diagnosing prostate cancer has been evaluated from various aspects and its performance has been compared with other learning models. Based on the results, the proposed method can diagnose prostate cancer through MRI images with an average accuracy of 99%. Discussion &amp; Conclusion: The proposed method uses a combination of image processing, optimization and machine learning techniques to achieve this goal. Compared with other models, this proposed method was of the highest accuracy.

Cardiorespiratory fitness and BMI in youth and site-specific cancer mortality in men: A population-based cohort study with register linkage.

10534 Background: There is insufficient evidence on the associations between cardiorespiratory fitness (CRF), body mass index (BMI), and site-specific cancer mortality. Methods: We collected data on all men who underwent military conscription 1968-2005 in Sweden at ages 16-25. CRF was assessed as maximal aerobic workload on a cycle ergometer test and classified as low, moderate, or high. BMI (kg/m2) was classified as underweight ( &lt; 18.5), normal weight (18.5-24.9), overweight (25-29.9), or obesity (≥30). Data was cross-linked on individual level through the Swedish identification number with national registers with high validity for information on cancer mortality. Follow-up was from conscription until death, emigration, or end of follow-up (12/31/2019). Cox regression analyses included CRF and BMI as well as age, year, and site of conscription, parental education, and muscle strength. Primary analyses tested linear trends for CRF and BMI, with effect sizes for categorical comparisons for interpretation. Results: 1,083,738 men were included in the analyses and were followed for a mean of 33 years, during which 8,912 cancer-specific deaths occurred. Lower CRF and higher BMI were linearly associated with any cancer mortality as well as with several site-specific cancer mortalities (table). However, death in some major cancer sites (prostate, CNS) were not associated with CRF or BMI and higher CRF was associated with higher mortality from malignant skin cancer. Conclusions: Higher CRF and lower BMI was associated with lower cancer mortality for some, but not all cancer sites. These results could be used as a further incentive for working with modifiable risk factors in public health. [Table: see text]

Abstract 1754: Targeting the mitochondrial protein MAGMAS increases sensitivity to docetaxel in neuroendocrine prostate cancer cells

Abstract Metastatic prostate cancer (PCa) is the leading cause of PCa-associated deaths and one of the leading causes of cancer mortality in men. Novel therapeutics, such as Prostate Specific Membrane Antigen (PSMA) ligand therapy, are emerging as effective treatment strategies for metastatic prostate cancer. However, neuroendocrine differentiated (NED) metastatic PCa, which lacks the PSMA antigen, is deprived of effective biomarkers for disease treatment. Magmas, a 13.8 kDa mitochondrial protein, imports nuclear-encoded mitochondrial proteins into the mitochondrial matrix. Magmas is overexpressed in several aggressive tumors, such as breast cancer, glioblastoma, and prostate cancer. When overexpressed, Magmas plays a role as a cytoprotective protein by acting as a reactive oxygen species (ROS) scavenger that maintains sufficient ROS levels to promote cell proliferation, but below the threshold levels that could lead to apoptosis. This study was designed to investigate the pro-survival and therapy-resistance functions of Magmas in PCa cells expressing NED markers. Predictively, we observed that the docetaxel (DTX)-resistant PC3-DR and DU145-DR PCa cell lines expressed significantly higher levels of Magmas compared to their drug-sensitive parental cell lines. We hypothesized that inhibiting Magmas reduces the aggressive properties of highly proliferative DTX- resistant metastatic PCa cell lines and re-sensitize them to DTX. Magmas knockdown in DTX-sensitive and DTX-resistant PC3 and DU145 cells in the presence of increasing DTX treatments enhanced sensitivity to DTX. Consistent with these results, pharmacological inhibition of Magmas with the novel BT#9 inhibitor in combination with increasing DTX concentrations also enhanced sensitivity to DTX in these cell lines. Additional studies using clonogenic assays, cell migration/invasion assays, and tumorsphere formation assays are currently underway to further establish Magmas as a potential therapeutic target to attenuate the aggressive properties of chemoresistant PCa cells. Lastly, we will investigate the diagnostic potential of Magmas as a biomarker for NED and BT#9 as an imaging/therapeutic-specific agent for NED. Citation Format: Alfonso M. Durán, Christian H. Yoo, Jennifer D. Tran, Krystal Santiago, Adil S. Mohammed, Carlos A. Casiano, Frankis A. Almaguel. Targeting the mitochondrial protein MAGMAS increases sensitivity to docetaxel in neuroendocrine prostate cancer cells [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 1754.

Identification of Bone Metastatic and Prognostic Alternative Splicing Signatures in Prostate Adenocarcinoma

As the most common nonepithelial malignancy, prostate adenocarcinoma (PRAD) is the fifth chief cause of cancer mortality in men. Distant metastasis often occurs in advanced PRAD and most patients are dying from it. However, the mechanism of PRAD progression and metastasis is still unclear. It’s widely reported that more than 94% of genes are selectively splicing in humans and many isoforms are particularly related with cancer progression and metastasis. Spliceosome mutations occur in a mutually exclusive manner in breast cancer, and different components of spliceosomes are targets of somatic mutations in different types of breast cancer. Existing evidence strongly supports the key role of alternative splicing in breast cancer biology, and innovative tools are being developed to use splicing events for diagnostic and therapeutic purposes. In order to identify if the PRAD metastasis is associated with alternative splicing events (ASEs), the RNA sequencing data and ASEs data of 500 PRAD patients were retrieved from The Cancer Genome Atlas (TCGA) and TCGASpliceSeq databases. By Lasso regression, five genes were screened to construct the prediction model, with a good reliability by ROC curve. Additionally, results in both univariate and multivariate Cox regression analysis confirmed the well prognosis efficacy of the prediction model (both P < 0.001). Moreover, a potential splicing regulatory network was established and after multiple-database validation, we supposed that the signaling axis of HSPB1 up-regulating the PIP5K1C − 46,721 − AT (P < 0.001) might mediate the tumorigenesis, progression and metastasis of PRAD via the key members of Alzheimer’s disease pathway (SRC, EGFR, MAPT, APP and PRKCA) (P < 0.001).

Associations of body size with all-cause and cause-specific mortality in healthy older adults

In the general population, body mass index (BMI) and waist circumference are recognized risk factors for several chronic diseases and all-cause mortality. However, whether these associations are the same for older adults is less clear. The association of baseline BMI and waist circumference with all-cause and cause-specific mortality was investigated in 18,209 Australian and US participants (mean age: 75.1 ± 4.5 years) from the ASPirin in Reducing Events in the Elderly (ASPREE) study, followed up for a median of 6.9 years (IQR: 5.7, 8.0). There were substantially different relationships observed in men and women. In men, the lowest risk of all-cause and cardiovascular mortality was observed with a BMI in the range 25.0–29.9 kg/m2 [HR25-29.9 vs 21–24.9 kg/m2: 0.85; 95% CI, 0.73–1.00] while the highest risk was in those who were underweight [HRBMI <21 kg/m2 vs BMI 21–24.9 kg/m2: 1.82; 95% CI 1.30–2.55], leading to a clear U-shaped relationship. In women, all-cause mortality was highest in those with the lowest BMI leading to a J-shaped relationship (HRBMI <21 kg/m2 vs BMI 21–24.9 kg/m2: 1.64; 95% CI 1.26–2.14). Waist circumference showed a weaker relationship with all-cause mortality in both men and women. There was little evidence of a relationship between either index of body size and subsequent cancer mortality in men or women, while non-cardiovascular non-cancer mortality was higher in underweight participants. For older men, being overweight was found to be associated with a lower risk of all-cause mortality, while among both men and women, a BMI in the underweight category was associated with a higher risk. Waist circumference alone had little association with all-cause or cause-specific mortality risk.Trial registration ASPREE https://ClinicalTrials.gov number NCT01038583.

Associations of Serum Folate and Homocysteine Concentrations with All-Cause, Cardiovascular Disease, and Cancer Mortality in Men and Women in Korea: the Cardiovascular Disease Association Study

BackgroundEvidence on the association of serum folate and homocysteine concentrations with risk of mortality in the general population is unclear. ObjectivesThis study aimed to examine the associations of serum folate and homocysteine concentrations with all-cause, CVD, and cancer mortality risk in Korean men and women aged ≥40 y. MethodsIn this population-based prospective cohort study, serum folate and homocysteine concentrations were measured in a subset of participants enrolled between 2005 and 2012. A total of 21,260 participants were linked to mortality data from the survey date to 31 December 2019. Cox proportional hazards models and restricted cubic splines were used to identify the associations of serum folate and homocysteine concentrations with mortality. ResultsDuring a median follow-up of 12.3 y, 2501, 549, and 842 deaths were attributed to all-cause, CVD, and cancer, respectively. The prevalence of folate deficiency and hyperhomocysteinemia were higher in men than in women. In men, a nonlinear inverse association was observed between serum folate concentrations and all-cause mortality. Men in the third quartile of serum folate concentrations exhibited a lower risk of all-cause mortality (HR: 0.85; 95% CI: 0.73, 0.99) than those in the lowest quartile. Serum homocysteine concentration was positively associated with all-cause and CVD mortality. Men and women in the highest compared with those in the lowest serum homocysteine quartile showed a higher risk of CVD mortality (HR: 1.60; 95% CI: 1.07, 2.39; and HR: 1.79; 95% CI: 1.11, 2.89, respectively). Hyperhomocysteinemia combined with folate deficiency was associated with increased all-cause, CVD, and cancer-related mortality rates. ConclusionsHigher serum homocysteine and lower serum folate concentrations were associated with an increased risk of all-cause, CVD, and cancer-related mortality in Korean adults. The finding of a nonlinear inverse relationship between serum folate concentration and mortality in men warrants further investigation.

Promoter Region Analysis of STAMP1/STEAP2 Gene-Silencing of STAMP1/STEAP2 Gene Triggers P53 Upregulation

Prostate cancer is the most commonly diagnosed cancer and the second leading cause of cancer mortality in men in the Western World. In the initial stages, prostate cancer is dependent on androgens for growth which is the basis for androgen ablation therapy. The effects of androgens are mediated by the Androgen Receptor (AR). Therefore, studies focus on the identification of AR-regulated genes that are also highly expressed in the prostate. STAMP family genes STAMP1/STEAP2 and STAMP2/STEAP4 have only expressed in androgen receptor-positive cells, the role of AR in STAMP family gene expression is an important question. STEAP (Six Transmembrane Epithelial Antigen of Prostate) is the first characterized prostate of enriched six transmembrane gene, expressed in metastatic prostate cancer samples, it is tempting to speculate that STAMP/STEAP family genes may be involved in similar functions with a role for both the normal biology and pathophysiology of the prostate. Using siRNA technology in LNCaP cells expressing STAMP genes per se, an apoptosis panel including pro-apoptotic and/or apoptotic molecules was assayed by RT-PCR, By this research project, prostate-specific STAMP gene family and its regulatory effects on the p53- and caspase-related pathways were characterized.

AGING: A SYSTEMATIC REVIEW ON THE CORRELATION BETWEEN GERIATRIC DISEASES AND PROSTATE CANCER

Prostate malignancy is a frequent carcinoma and is the 2nd common in adult males accounting for about 3.8% of all cancer mortality in men in 2018; this has been linked to older men around 70 years old (≥70). About 2,293,818 new diagnoses are anticipated by 2040, considering the disparity in Social, environmental, and genetic factors, which also has a significant role in this disease. Geriatric syndromes are clinical state and are mostly common in elderly people, especially frail older adults; these conditions are not always associated with a certain underlying disease. The study aims to give a brief review of Prostatic Carcinoma, Geriatric diseases and also discuss the correlation between aging and prostate malignancy. As obtained from different studies, malignancy is primarily a disease of older adults, with patients over 65 accounting for most cancer diagnoses and deaths. The elongation of life is a significant challenge related to more medical conditions, and due to an increase in lifespan, the figure of elderly patients with prostate malignancy will increase. It was concluded that as we emerge from the baby boomer generation, the figure of elderly males with prostate malignancy will keep increasing. However, comprehensive geriatric evaluation and pertinent disease staging at diagnosis will aid adequately manage these patients. This method will assist us in recommending the best course of action, focusing on maintaining the quality of life.