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Background Cardiovascular disease (CVD) and cancer frequently co‐occur due to shared risk factors such as obesity, which is linked to CVD and 14 cancer types. This study explores whether CVD pathophysiologies, combined with obesity, increase cancer risk, impacting clinical management. Methods and Results Data from the ARIC (Atherosclerosis Risk in Communities) study, spanning 28 years, were analyzed. The cohort included 5127 participants with incident CVD (myocardial infarction, stroke, heart failure, coronary heart disease), of whom 1511 developed a first primary cancer. Follow‐up began at CVD diagnosis after Visit 1. Obesity was assessed using body mass index, waist circumference, and waist‐to‐hip ratio. Incidence rate differences between obesity groups were adjusted for age, sex, and center, whereas the obesity–cancer association was estimated using Fine‐Gray regression adjusted for shared risk factors including smoking. Cancer incidence in obese individuals with CVD (body mass index: rate differences=226.6/100 000 person‐years) was higher than in those with normal weight. Although obesity was not linked to overall cancer after adjusting for shared risk factors, it was nominally associated with obesity‐related cancers. Specifically, women with CVD and obesity had increased obesity‐related cancer risk (body mass index: hazard ratio, 1.67 [95% CI, 1.17–2.31]). No significant associations were found in men, even after excluding prostate cancer. Conclusions This study suggests that obesity is linked to higher obesity‐related cancer risk in women with incident CVD, independent of shared risk factors. Further research is needed to eliminate residual confounding, understand sex differences, and explore how CVD pathophysiologies and obesity together influence cancer risk.

Abstract Ginger has been associated with a decreased incidence of colorectal cancer (CRC) through reduction in inflammatory pathways and inhibition of tumor growth. Recent pre-clinical models have implicated changes in the gut microbiome as a possible mediator of the ginger effect on CRC. We hypothesized that, in adults previously diagnosed with a colorectal adenoma, ginger supplementation would alter the fecal microbiome in the direction consistent with its CRC-inhibitory effect. Sixty-eight adults were randomized to take either ginger or placebo daily for 6 weeks, with a 6-week washout and longitudinal stool collection throughout. We performed 16S rRNA sequencing and evaluated changes in overall microbial diversity and the relative abundances of pre-specified CRC-associated taxa using mixed-effects logistic regression. Ginger supplementation showed no significant effect on microbial community structure through alpha or beta diversity. Of 10 pre-specified CRC-associated taxa, there were significant decreases in the relative abundances of the genera Akkermansia (p

Factors driving accelerated biological age (BA), an important predictor of chronic diseases, remain poorly understood. This study focuses on the impact of diet and gut microbiome on accelerated BA. Accelerated Klemera–Doubal biological age (KDM-BA) was estimated as the difference between KDM-BA and chronological age. We assessed the cross-sectional association between accelerated KDM-BA and diet/gut microbiome in 117 adult participants from the 10,000 Families Study. 16S rRNA sequencing was used to estimate the abundances of gut bacterial genera. Multivariable linear mixed models evaluated the associations between accelerated KDM-BA and diet/gut microbiome after adjusting for family relatedness, diet, age, sex, smoking status, alcohol intake, and BMI. One standard deviation (SD) increase in processed meat was associated with a 1.91-year increase in accelerated KDM-BA (p = 0.04), while one SD increase in fiber intake was associated with a 0.70-year decrease in accelerated KDM-BA (p = 0.01). Accelerated KDM-BA was positively associated with Streptococcus and negatively associated with Subdoligranulum, unclassified Bacteroidetes, and Burkholderiales. Adjustment for gut microbiome did not change the association between dietary fiber and accelerated KDM-BA, but the association with processed meat intake became nonsignificant. These cross-sectional associations between higher meat intake, lower fiber intake, and accelerated BA need validation in longitudinal studies.

The population of cancer survivors has markedly increased due to the rapid improvements in cancer treatment. However, cancer survivors experience accelerated aging, which leads to chronic diseases and other age-related conditions, such as frailty. Those conditions may persist years after cancer diagnosis and treatment. Cellular senescence, a hallmark of aging, is one of the mechanisms that contribute to accelerated aging in cancer survivors. Several aging measures, including measures based on clinical markers and biomarkers, have been proposed to estimate the aging process, and some of them have shown associations with mortality and frailty in cancer survivors. Several anti-aging interventions, including lifestyle changes and anti-aging drugs, have been proposed. Future research, particularly in large-scale studies, is needed to determine the efficiency of these aging measures and anti-aging interventions before considering their application in clinics. This review focuses on the mechanisms of cellular senescence and accelerated aging in cancer survivors, assessment of the aging process using clinical markers and biomarkers, and the high prevalence of frailty in that population, as well as possible opportunities for anti-aging interventions. A deeper understanding of aging measures and anti-aging interventions in cancer survivors will contribute to the development of effective strategies to mitigate accelerated aging in cancer survivors and improve their quality of life.

IntroductionAge-related immunosenescence is characterized by changes in immune cell subsets and is associated with mortality. However, since immunosenescence is associated with other concurrent age-related changes such as inflammation and multi-organ dysfunction, it is unclear whether the association between age-related immunosenescence and mortality is independent of other concurrent age-related changes. To address these limitations, we evaluated the independent association between immune cell subsets and mortality after adjustment for age-related inflammation and biologic age.MethodsData for this study was obtained from the 2016 interview of the Health and Retirement Study (N=6802). Cox proportional hazards regression models were used to estimate the association between 25 immune cell subsets (11 T-cell subsets, 4 B-cell subsets, 3 monocyte subsets, 3 natural killer cell subsets, 3 dendritic cell subsets, and neutrophils) and 4-year mortality adjusting for covariates such as the Klemera-Doubal algorithm biological age, chronological age, gender, race/ethnicity, BMI, smoking status, comorbidity index, CMV seropositivity, and inflammatory latent variable comprising C-reactive protein, and 4 cytokines (interleukin-10, interleukin-1 receptor antagonist, interleukin-6, and soluble tumor necrosis factor).ResultsFour hundred and seventy-six participants died during the study period with an overall median follow up time of 2.5 years. After controlling for covariates and adjustment for sample-weights, total T cells [HR: 0.86, p=0.004], NK CD56LO cells [HR: 0.88, p=0.005], and neutrophils [HR: 1.22, p=0.004] were significantly associated with mortality.ConclusionsThese findings support the idea that an aging immune system is associated with short-term mortality independent of age-related inflammation or other age-related measures of physiological dysfunction. If replicated in other external cohorts, these findings could identify novel targets for both monitoring and intervention to reduce the age-related mortality.

The androgen receptor (AR) signaling pathway regulates the progression of prostate cancer (PC). Metastatic castration-resistant prostate cancer (mCRPC) patients generally receive AR-targeted therapies (ART) or androgen-deprivation therapies (ADT) with the initial response; however, resistance is inevitably observed. Prior studies have shown activity and upregulation of a family of androgen production, uptake, and conversion – APUC genes – based on genomic analyses of patient germlines. Genetic variants of some APUC genes, such as the conversion gene, HSD3B1, predict response to second-generation androgen-targeted therapies. Studies have begun to elucidate the overall role of APUC genes, each with unique actionable enzymatic activity, in mCRPC patient outcomes. The current role and knowledge of the genetic and genomic features of APUC genes in advanced prostate cancer and beyond are discussed in this review. These studies inform of how interpreting behavior of APUC genes through genomic tools will impact the treatment of advanced prostate cancer.

Background: The major histocompatibility complex class I polypeptide-related sequence A (MICA) is one of the ligands of the natural killer group 2D (NKG2D) activating receptor. MICA stimulates NKG2D, which further triggers activation of natural killer cells and leads to killing of infected target cells. To subvert the biological function of NKG2D, tumor cells utilize an escape strategy by shedding overexpressed MICA. In this study, we determined the levels of MICA in colorectal cancers (CRCs). Additionally, we established correlations between MICA expression and clinical characteristics. Publicly available data and bioinformatics tools were used for validation purposes. Methods: We determined the MICA RNA expression levels and assessed their correlation with clinicopathological parameters in CRC using the UALCAN web-portal. We performed immunohistochemical analysis on tissue microarrays having 192 samples, acquired from 96 CRC patients, to validate the expression of MICA in CRC and adjacent uninvolved tissue and investigated its prognostic significance by Kaplan-Meier and proportional hazards methods. Results: Bioinformatics and immunohistochemical analyses showed that MICA expression was significantly upregulated in CRCs as compared to uninvolved tissue, and the overexpression of MICA was independent of pathologic stage, histotype, nodal metastasis status, p53-status, as well as patient’s race, age and gender. Moreover, PROGgeneV2 survival analysis of two cohorts showed a poor prognosis for CRC patients exhibiting high MICA expression. Conclusions: Overall, our findings for CRC patients demonstrate generally high expression of MICA, and suggest that a poor prognosis relates to high MICA expression. These results can be further explored due to their potential to provide clues to the contribution of the tumor microenvironment to the progression of CRC.