Independent Risk Factor For Cancer Research Articles

Obstructive sleep apnea severity, circulating biomarkers, and cancer risk.

To determine if obstructive sleep apnea (OSA) severity and/or biomarkers of inflammation/angiogenesis are associated with incident cancer in this clinical cohort. Consenting adult patients at the University of British Columbia Hospital between 2003-2014 completed a questionnaire about their medical history and sleep habits prior to undergoing a polysomnogram (PSG). Blood samples were collected the morning after PSG and processed for biomarkers of inflammation and angiogenesis. The clinical, PSG, and biomarker data were linked to the British Columbia Cancer Registry to ascertain incident cancer diagnoses. Cox proportional hazard regression were used to assess the association between OSA severity and biomarker concentrations with cancer risk. A total of 1,990 patients were included in the analysis with a mean follow-up time of 12.8 years; 181 of them (9.1%) developed cancer after PSG. OSA severity was significantly associated with cancer risk after controlling for relevant covariates (hazard ratio (HR) = 1.08 per 10 events/h apnea-hypopnea index (AHI) increase, CI = 1.02-1.15, p=0.015). In an exploratory analysis, two biomarkers were significantly associated with an increased cancer risk after controlling for relevant covariates (HR per interquartile range (IQR) pg/mL increase of endostatin = 1.45, CI = 1.12-1.87, p=0.01 and HR for IQR pg/mL increase of VCAM-1 = 1.48, CI = 1.04-2.11, p=0.03, respectively). OSA severity was an independent risk factor for cancer. Furthermore, two circulating markers were significantly associated with cancer risk. If these preliminary findings can be reproduced in other cohorts, biomarkers could potentially be used to prognosticate OSA patients with respect to cancer risk.

Abstract 4796: Improving cancer screening performance for women with dense breast tissue

Abstract Breast cancer is the most common cancer in women in the United States. To reduce mortality, screening by mammography in females is recommended by the United States Preventive Services Task Force, successfully reducing mortality by 15 - 32% in women aged 40 - 69 years. This is partially due to the high compliance rate (60 - 80%) among the candidate population. Mammography increases early-stage disease detection, which is correlated with better outcomes. While mammography has been largely successful, this screening method has limitations. Overall, mammography has false-negative and false-positive rates estimated at 12 - 20% and 7 - 12%, respectively. Consequently, annual mammograms result in 50 - 60% of women having a false-positive result within a 10-year span. Additionally, high breast density, found in approximately 50% of females over the age of 40, increases susceptibility to false positive and negative results. For this reason, in 2023 the FDA required that dense breast tissue status, an independent risk factor for cancer, be disclosed to mammogram recipients. The subsequent diagnostic pathway for women with dense breast tissue is not well defined for the care provider. Alternative imaging options have performance issues or are less accessible. Here we describe a liquid biopsy test to complement mammography in women with dense breast tissue to help resolve ambiguity in results. Blood from early- and late-stage breast cancer patients was prospectively collected in Streck cfDNA BCT Devices (n=100) or retrospectively acquired (n=100); and blood from presumed normal samples was collected (n=200). cfDNA was extracted and converted into libraries for low-pass whole genome sequencing (LP-WGS). Sequenced reads were analyzed to generate fragment end-motif and size (FEMS) and fragment coverage dataframes for classification using Genece Health’s proprietary analysis pipeline and machine-learning (ML) algorithm. 150 breast cancer samples distributed across stages and 150 presumed normal samples were selected to create a training cohort. Performance was tested using a 5-fold cross validation strategy. The best performance was observed using a convolution neural network (CNN) ML model with >80% sensitivity when specificity was set at 85%. The remaining 50 breast cancer samples and 50 presumed normal samples were used as an external test set. The performance in this cohort was comparable to the training cohort, with both specificity and sensitivity >80%. Genece presents an early proof of concept breast cancer screening liquid biopsy assay that uses LP-WGS fragmentomics and ML to detect cancer from a single blood sample. Continuing development with additional cohorts and optimization will yield even greater performance. The Genece liquid biopsy test has the potential to be paired with mammography, especially in women with dense breast tissue, to improve screening sensitivity, specificity, and overall outcomes. Citation Format: Molly Smith, Mengchi Wang, Andrew Carson, Byung In Lee, Michael Salmans, Bryan Leatham. Improving cancer screening performance for women with dense breast tissue [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 4796.

Overview: Global burden of liver disease

About 2 million deaths occur annually, and 4% of all deaths are caused by liver disease, which ranks as the 11 leading cause of death worldwide. This review includes the different kinds of liver disorders and their global prevalence. It focuses primarily on areas where significant new data is available, such as drug-induced liver injury, acute chronic liver disease, hepatocellular carcinoma, non-alcoholic fatty liver disease, alcoholic liver disease, and viral hepatitis. Most deaths are attributed to complications arising from hepatocellular carcinoma and cirrhosis. Obesity in Early life is an independent risk factor for cancer and cirrhosis. In the western world, alcohol is the primary cause of liver cirrhosis. It also covers some special considerations, such as hepatic conditions during COVID-19 and pregnancy, with a retrospective study. Additionally, we cover important data on sign symptoms, prevention, diagnosis with specialized techniques, and treatment with various drugs.

Multi-omics and single-cell sequencing analyses reveal the potential significance of circadian pathways in cancer therapy

ABSTRACT Background Circadian rhythm disturbance is an independent risk factor for cancer. However, few studies have been reported on circadian rhythm related genes (CRGs) in cancer, so it is important to further explore the impact of CRGs in pan-cancer. Research design and methods The Cancer Genome Atlas database was used to collect cancer-related data such as copy number variation, single nucleotide variants, methylation, and survival differences. Immunohistochemistry (IHC) was used to verify the expression of circadian rhythm hub genes. The circadian pathway scores (CRS) were calculated using single-sample gene enrichment analysis. TIMER and GEPIA databases were used for immune-cell integration and assessment. Single-cell sequencing data was used to evaluate the abundance of CRS in tumor microenvironment cells. Results In this study, we found that the expression of circadian pathway varies between tumors. CSNK1E was significantly up-regulated in most tumors and CRY2 was significantly down-regulated in most tumors. The protein interaction network suggested CRY2 as the core gene and IHC verified its significant low expression in KIRC. In addition, CRGs were found to be protective factors in most tumors and have the potential to act as specific immune markers in different tumors. CRS was significantly lower in abundance in most tumors. CRS was significantly associated with overall survival in tumor patients and associated with the expression of many immune cells in the tumor immune microenvironment. CRS is significantly associated with tumor mutational burden and microsatellite instability scores in most tumors and may serve as a potential immunotherapeutic marker. Conclusions The circadian rhythm pathway may be a breakthrough point in regulating the tumor microenvironment meanwhile a suitable immunotherapy method in the future.

Hyperinsulinemia acts via acinar insulin receptors to initiate pancreatic cancer by increasing digestive enzyme production and inflammation

The rising pancreatic cancer incidence due to obesity and type 2 diabetes is closely tied to hyperinsulinemia, an independent cancer risk factor. Previous studies demonstrated reducing insulin production suppressed pancreatic intraepithelial neoplasia (PanIN) pre-cancerous lesions in Kras-mutant mice. However, the pathophysiological and molecular mechanisms remained unknown, and in particular it was unclear whether hyperinsulinemia affected PanIN precursor cells directly or indirectly. Here, we demonstrate that insulin receptors (Insr) in KrasG12D-expressing pancreatic acinar cells are dispensable for glucose homeostasis but necessary for hyperinsulinemia-driven PanIN formation in the context of diet-induced hyperinsulinemia and obesity. Mechanistically, this was attributed to amplified digestive enzyme protein translation, triggering of local inflammation, and PanIN metaplasia invivo. Invitro, insulin dose-dependently increased acinar-to-ductal metaplasia formation in a trypsin- and Insr-dependent manner. Collectively, our data shed light on the mechanisms connecting obesity-driven hyperinsulinemia and pancreatic cancer development.

Interactions of circadian clock genes with the hallmarks of cancer

The molecular machinery of the circadian clock regulates the expression of many genes and processes in the organism, allowing the adaptation of cellular activities to the daily light-dark cycles. Disruption of the circadian rhythm can lead to various pathologies, including cancer. Thus, disturbance of the normal circadian clock at both genetic and environmental levels has been described as an independent risk factor for cancer. In addition, researchers have proposed that circadian genes may have a tissue-dependent and/or context-dependent role in tumorigenesis and may function both as tumor suppressors and oncogenes. Finally, circadian clock core genes may trigger or at least be involved in different hallmarks of cancer. Hence, expanding the knowledge of the molecular basis of the circadian clock would be helpful to identify new prognostic markers of tumorigenesis and potential therapeutic targets.

A novel cuproptosis-related prognostic gene signature and validation of differential expression in hepatocellular carcinoma.

Background: Cuproptosis is a newly discovered form of programmed cell death, which is characterized by accumulation of intra-cellular copper ion leading to the aggregation of lipoproteins and destabilization of Fe-S cluster proteins in mitochondrial metabolism, thereby affecting the prognosis of patients with cancer. However, the role of cuproptosis-related genes (CRGs) in hepatocellular carcinoma (HCC) remains elusive. Methods: Mutation signature, copy number variation and the expression of 10 CRGs were assessed in HCC from TCGA-LIHC dataset. ICGC-LIRI-JP dataset was used as further validation cohort. The least absolute shrinkage and selection operator (LASSO) was used to construct the prognostic model. Kaplan Meier curves, time-ROC curves, nomogram, univariate and multivariate Cox regression were utilized to evaluate the predictive efficacy of CRGs-score. Immune infiltration was analyzed by CIBERSOFT, ssGSEA algorithm, and TIMER database. The expression of prognostic CRGs was validated by qPCR both in-vitro and in-vivo. Drug sensitivity analysis was performed by pRRophetic. Results: All of the CRGs were differentially expressed in HCC and 5 out of them (CDKN2A, DLAT, GLS, LIPT1, MTF1) correlated with patient survival. These signature genes were selected by LASSO analysis to establish a prognosis model to stratify HCC patients into high and low CRGs-score subgroups. High CRGs-score was associated with a worse prognosis. Subsequently, univariate and multivariate Cox regression verified that CRGs-score was an independent cancer risk factor that correlated with clinical factors including stage and grade. Nomogram integrating the CRGs-score and clinical risk factors performed well to predict patient survival. Immune infiltration analysis further revealed that the expression of immune checkpoint genes was significantly enhanced in high CRGs-score group, especially PD-1 and PD-L1. An independent validation cohort (ICGC) confirmed that CRGs-score as a stable and universally applicable indicator in predicting HCC patient survival. Concordantly, the expression of five confirmed signature genes were also differentially expressed in human HCC cell lines and mouse HCC model. In addition, we also analyzed the sensitivity of 10 clinical targeted therapies between high and low CRGs-score groups. Conclusion: This study elucidated the role of dysregulated CRGs in HCC cohort, with validation with in-vitro and in-vivo models. The CRGs-score might be applied as a novel prognostic factor in HCC.

Protein Disulfide Isomerases Function as the Missing Link Between Diabetes and Cancer.

Significance: Diabetes has long been recognized as an independent risk factor for cancer, but there is insufficient mechanistic understanding of biological mediators that bridge two disorders together. Understanding the pathogenic association between diabetes and cancer has become the focus of many studies, and findings are potentially valuable for the development of effective preventive or therapeutic strategies for both disorders. Recent Advances: A summary of literature reveals a possible connection between diabetes and cancer through the family of protein disulfide isomerase (PDI). Historical as well as the most recent findings on the structure, biochemistry, and biology of the PDI family were summarized in this review. Critical Issues: PDIs in general function as redox enzymes and protein chaperones to control the quality of proteins by correcting or otherwise eliminating misfolded proteins in conditions of oxidative stress and endoplasmic reticulum stress, respectively. However, individual members of the PDI family may contribute uniquely to the pathogenesis of diabetes and cancer. Studies of exemplary members such as protein disulfide isomerase-associated (PDIA) 1, PDIA6, and PDIA15 were reviewed to highlight their contributions in the pathogenesis of diabetes and cancer and how they can be potential links bridging the two disorders through the cross talk of signaling pathways. Future Directions: Apparently ubiquitous presence of the PDIs creates difficulties and challenges for scientific community to develop targeted therapeutics for the treatment of diabetes and cancer simultaneously. Understanding molecular contribution of individual PDI in the context of specific disease may provide some insights into the development of mechanism-based target-directed therapeutics. Antioxid. Redox Signal. 37, 1191-1205.

Extracellular vesicles from the infarcted and failing heart drive tumor growth

Abstract Aims Heart disease might be an independent risk factor for cancer (reverse cardio-oncology). The co-occurrence of these diseases worsens patients' prognoses and limits therapeutic options. However, the cellular and molecular mechanisms that link heart disease to cancer remain elusive. Therefore, we hypothesized that cardiac extracellular vesicles (cEVs) secreted by diseased hearts carry and disseminate factors that promote tumor growth. Methods and results We subjected female mice to myocardial infarction (MI) or sham-MI and 28 days of follow-up. Left ventricular remodeling and dysfunction were assessed by echocardiography. To determine the role of cEVs in tumor growth, we focused on cardiac mesenchymal stromal cells (cMSCs), which play a central role in cardiac repair, remodeling, and fibrosis. We isolated cMSCs from mice hearts 10 or 28 days after MI or sham MI and purified cMSC-EVs from the conditioned medium using size exclusion chromatography. cEVs were characterized by nanoparticle tracking analysis (NTA), the classical EV markers: CD81 and Tumor susceptibility gene 101, and electron microscopy. cMSCs after MI secreted more small EVs than cMSCs from sham-MI (Fig. 1A, p<0.0001). Proteomic and biological process analysis revealed a distinctive profile of cEVs after MI with more EV-encapsulated proteins related to inflammation, angiogenesis, and cell cycle (Fig. 1B). Purified cMSC-EVs were labeled with PKH26 dye and found to target both breast and lung cancer cells in vitro. Colorimetric proliferation assay showed that MI-cEVs facilitated cancer cells proliferation compared with sham-MI cEVs (n=7 in each group, p<0.0001). Furthermore, by scratch assay, MI-cEVs facilitated cancer cell migration two times faster than sham-MI cEVs (Fig. 1C, p=0.0002). Finally, we established 2 models of heart disease with cancer. Lung or breast cancer cells (750x103 or 250x103) were inoculated into the hind limb or mammary pad 10 days before or after MI. Serial ultrasound examinations monitored tumor growth. While MI significantly stimulated lung cancer growth, EV inhibition by GW4869 markedly attenuated the tumorigenic effect of MI and left ventricular (LV) dysfunction (Fig. 1D, p for GW4869 <0.0001). Moreover, we found an inverse correlation between LV ejection fraction (LVEF) and the volume of breast cancer tumors. cEV inhibition by GW4869 attenuated this inverse correlation (for vehicle group: n=14, r=−0.54 and p=0.04. for GW4869 group: n=13, r=−0.43, and p=0.14). Conclusions Our results suggest, for the first time, that cMSCs from the infarcted and failing heart secret EVs that target tumor cells and accelerate tumor growth. We propose cEVs as potential mediators and therapeutic targets in patients with concomitant heart disease and cancer. Funding Acknowledgement Type of funding sources: Private grant(s) and/or Sponsorship. Main funding source(s): Seymour Fefer Grant

Effect of sleep disorders on the risks of cancers and site-specific cancers

PurposeWhether preexisting sleep disorder is an independent risk factor for cancer remains unclear. Therefore, we performed this propensity score–matched population-based cohort study to compare the incidence rate ratios (IRRs) of specific cancers between patients with and without sleep disorders. Patients and methodsPatients were categorized into two groups on the basis of the presence or absence of sleep disorders and matched at a 1:1 ratio. ResultsPropensity score matching yielded a final cohort of 289,162 patients (i.e., 144,581 and 144,581 in the sleep disorder and nonsleep disorder groups, respectively) who were eligible for further analysis. In multivariate Cox regression analysis, the adjusted hazard ratio (aHR; 95% confidence interval [CI]) of cancer risk in the sleep disorder group compared with the nonsleep disorder group was 1.07 (1.04–1.12; P = 0.0001). Furthermore, the adjusted IRRs (95% CIs) for all cancers, breast cancer, and ovarian cancer in the patients with sleep disorders were 1.08 (1.02–1.18), 1.20 (1.08–1.32), and 1.30 (1.10–1.52), respectively. ConclusionThe results suggested that sleep disorders are a significant risk factor for all cancers, breast cancer, and ovarian cancer.

Development and Validation of a Novel Circadian Rhythm-Related Signature to Predict the Prognosis of the Patients with Hepatocellular Carcinoma.

Hepatocellular carcinoma (HCC) is one of the most important causes of cancer-related deaths and remains a major public health challenge worldwide. Considering the extensive heterogeneity of HCC, more accurate prognostic models are imperative. The circadian genes regulate the daily oscillations of key biological processes, such as nutrient metabolism in the liver. Circadian rhythm disruption has recently been recognized as an independent risk factor for cancer. In this study, The Cancer Genome Atlas (TCGA) and Genotype-Tissue Expression (GTEx) were compared and 248 differentially expressed genes (DEGs) of the circadian rhythm were identified. HCC was classified into two subtypes based on these DEGs. The prognostic value of each circadian rhythm-associated gene (CRG) for survival was assessed by constructing a multigene signature from TCGA cohort. A 6-gene signature was created by applying the least absolute shrinkage and selection operator (LASSO) Cox regression method, and all patients in TCGA cohort were divided into high- and low-risk groups according to their risk scores. The survival rate of patients with HCC in the low-risk group was significantly higher than that in the high-risk group (p < 0.001). The patients with HCC in the Gene Expression Omnibus (GEO) cohort were also divided into two risk subgroups using the risk score of TCGA cohort, and the overall survival time (OS) was prolonged in the low-risk group (p = 0.012). Based on the clinical characteristics, the risk score was an independent predictor of OS in the patients with HCC. The Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses showed that multiple metabolic pathways, cell cycle, etc., were enhanced in the high-risk group. Using the metabolic pathway single-sample gene set enrichment analysis (ssGSEA), it was found that the metabolic pathways in the high- and low-risk groups between TCGA and GEO cohorts were altered essentially in the same way. In conclusion, the circadian genes play an important role in HCC metabolic rearrangements and can be further used to predict the prognosis the patients with HCC.

Abstract P3104: Extracellular Vesicles From The Infarcted Heart Facilitate Tumor Growth

Background and Aim: Heart disease might be an independent risk factor for cancer (reverse cardio-oncology). The cellular and molecular mechanisms that link heart disease to cancer remain elusive, and specific therapies are limited. We hypothesized that cardiac extracellular vesicles (cEVs) secreted by diseased hearts carry and disseminate factors that promote tumor growth. Methods &amp; Results: We subjected female mice to myocardial infarction (MI) or sham-MI and 28 days of follow-up. Left ventricular remodeling was confirmed by echocardiography. To determine the role of cEVs in tumor growth, we focused on cardiac mesenchymal stromal cells (cMSCs), which play a central role in cardiac repair, remodeling, and fibrosis. Thus, we isolated cMSCs from mice hearts 10 or 28 days after MI or sham MI. cMSCs after MI secreted more small EVs than cMSCs from sham-MI. Proteomic analysis revealed a distinctive profile of cEVs after MI ( Fig A ). Purified cMSC-EVs targeted both breast and lung cancer cells in vitro. A scratch assay showed that MI-cEVs facilitated cancer cell proliferation and migration two times faster than sham-MI cEVs ( Fig B , p=0.0002). Finally, lung or breast cancer cells were inoculated into the hind limb or mammary pad 10 days before or after MI. Tumor growth was monitored by serial ultrasound examinations. While MI stimulated tumor growth, EV inhibition by GW4869 markedly attenuated this effect ( Fig C ). Conclusions: We show, for the first time, that cMSCs from the infarcted and remodeling heart secret EVs that target tumor cells and facilitate tumor growth. We propose cEVs as potential mediators and therapeutic targets in patients with concomitant heart disease and cancer.

Influence of typeII diabetes mellitus on postoperative complications following colorectal cancer surgery.

Diabetes mellitus (DM) promotes colorectal cancer (CRC) carcinogenesis through complex processes and is considered as an independent risk factor for cancer in general and for CRC in particular. Diabetic patients have complications in the postoperative period following CRC surgery. The aim of the present study was to explore the effect of type II DM (T2DM) on postoperative outcomes for CRC compared with non-diabetic patients. The present study analyzed the data from patients admitted to the General Surgery Department, Emergency Hospital of Constanța (Romania) diagnosed with CRC and DM compared with a control group (patients with CRC, without DM, recruited in the same period and frequency matched to cases by number, sex and age) analyzing patient comorbidities and postoperative complications. A total of 61 patients had undergone surgery for CRC and met the inclusion criteria in the present study conducted during September 2020-2021. A total of 30 patients associated T2DM. Diabetic patients have been associated with more comorbidities than non-diabetics; the age-adjusted Charlson comorbidity index score ≥6 was identified in 90% of diabetic patients compared with 45.2% of controls. Grade III Clavien-Dindo classification was observed in 13.3% diabetic patients compared with 3.2% of non-diabetic patients. Additionally, a higher rate of urinary and pulmonary complications (6.7 vs. 3.2% in controls respectively) in patients with diabetes was found. Postoperative hospitalization was prolonged in diabetic patients (P=0.042). Univariate and multivariate analyses revealed that the laparoscopic approach for diabetic patients was found to be associated with <grade III Clavien-Dindo classification (P=0.040) and the absence of surgical site infection (P=0.040). Diabetes predisposes patients to numerous postoperative complications following CRC surgery and postoperative therapeutic conduct must be personalized to prevent possible postoperative complications following CRC.

Diabetes Is an Independent Risk Factor for Cancer after Heart and/or Lung Transplantation.

Background: De novo cancers are feared complications after heart or lung transplantation. Recent data suggest that diabetes mellitus (DM) might also be a risk factor for cancer. We hypothesized that transplanted diabetic patients are at greater risk of developing cancer compared to non-diabetic ones. Methods: We reviewed 353 patients post-heart and/or -lung transplantation from our center between October 1999 and June 2021. Patients with follow-up <180 days (n = 87) were excluded from the analysis. The remaining 266 patients were divided into patients who had preoperative DM (n = 88) or developed it during follow-up (n = 40) and patients without DM (n = 138). Results: The diabetic cohort showed higher rates of malignancies in all patients (30.33 vs. 15.97%, p = 0.005) and in the matched population (31.9 vs. 16.1%, p < 0.001). There were also significantly more solid tumors (17.9 vs. 9.4%, p = 0.042; matched: 16.6 vs. 9.1%, p = 0.09) The presence of diabetes was associated with a 13% increased risk of cancer when compared to non-diabetic patients. New-onset post-transplant diabetes doubled the likelihood of cancer development. Conclusions: Pre-transplant diabetes mellitus increases the risk of cancer after heart and/or lung transplantation. However, new-onset diabetes after transplantation is associated with a much greater cancer risk. This information is relevant for screening during follow-up.

MO1018: Nephrotic Syndrome as a Paraneoplastic Entity

Abstract BACKGROUND AND AIMS Association between nephrotic syndrome (NS) and cancer is well known. However, it has been barely studied and sustained. Membranous nephropathy (MN) has often been identified as a glomerular paraneoplastic disease. Reported incidence of cancer at the time of biopsy or one year follow-up of MN is 10–20%. Incidence rates in other glomerulopathies are limited. Concomitant malignancy is associated with poor renal outcome in NS since therapy for cancer is a priority and immunosuppressive therapies for NS should be restricted. There is no consensus for cancer screening in patients with NS, with or without known risk factors for cancer. Our aim is to establish the incidence of neoplasia in a cohort of patients of two tertiary hospitals in Spain who develop NS. We analyze clinical characteristics, glomerular disease, types of malignancies and risk factors for cancer in this population. METHOD All patients &amp;gt; 18 years old with NS at one tertiary hospital in Madrid between January 2013 and December 2019 and at one tertiary hospital in Barcelona between January 2018 and June 2020 were included. Demographical and clinical data, laboratory results, and tests performed for cancer screening were recorded. Patients who presented cancer the year before or 24 months after the diagnosis of NS were identified. We performed a logistic regression model to identify independent risk factors for cancer in this population. RESULTS A total of 114 patients presented with NS during the study periods. A total of 57% were men, and the mean age was 57.28 ± 17.3 years. A total of 60% patients presented high blood pressure and 36% type 2 DM2; 7% patients presented HIV infection and 6% hepatitis C infection. A total of 44.7% reported smoking and 13.1% of alcohol consumption. More frequent histologic diagnosis were: diabetic nephropathy (17.5%), MN (14.9%), minimal change disease (7.9%) and membranoproliferative glomerulonephritis (7.9%). Eight patients presented positivity for anti-phospholipase A2 receptor antibodies. A total of 20 patients presented cancer (17.5%): 12 patients had a malignancy diagnosed the year before the NS onset (10 patients with solid organ malignancy and 2 patients with haematological cancer) and 8 patients 24 months after NS onset (3 patients with solid organ malignancy and 5 patients with haematological cancer). In the univariate analysis, patients with cancer were older (72.35 ± 10.28 versus 53.20 ± 17.13 years old; P &amp;lt; .0001). There were no differences in terms of smoking, viral infections, renal function, proteinuria or type of glomerulopathy. In a multivariate analysis, age was the only risk factor for cancer in patients with NS {OR = 1.122, [95% confidence interval (95% CI) 1.050–1.1980]; P = .0007}. Patients who were diagnosed with cancer were submitted more frequently to gastroscopy (50% versus 25.5%; P = .0323), colonoscopy (60% versus 26.6%; P = .038) and mammography (30% versus 11.7%; P = .370) as screening procedures for malignancy than those without cancer diagnosis. There were no differences in other screening procedures such as chest X-ray, fecal occult blood test, CT scan or abdominal ultrasound. CONCLUSION In our cohort, 17.5% patients with NS presented also concomitant cancer. Age was the only risk factor for neoplasia in this cohort. No association between cancer and gender, type of glomerulopathy, or known risk factors for neoplasia such as alcohol, tobacco or viral infection was found. Patients who were diagnosed with cancer were more frequently submitted to specific cancer screening procedures. It is important to develop screening strategies to find occult malignancy in patients with NS since this condition compromises renal outcome and life expectancy.

Coronary Atherosclerotic Disease and Cancer: Risk Factors and Interrelation.

BackgroundIn our clinical work, we found that cancer patients were susceptible to coronary atherosclerotic heart disease (CAD). However, less is known about the relationship between CAD and cancer. The present study aimed to identify the risk factors for CAD and cancer, as well as the relationship between CAD and cancer.MethodsIn this retrospective study, 1600 patients between January 2012 and June 2019 were enrolled and divided into groups according to whether they had CAD or cancer. Single-factor and multivariate analysis methods were applied to examine the risk factors for CAD and cancer.Results(1) Cancer prevalence was significantly higher in patients with CAD than in patients without CAD (47.2 vs. 20.9%). The prevalence of CAD in cancer and non-cancer patients was 78.9 and 52.4%, respectively. (2) Multivariable logistic regression showed that patients with cancer had a higher risk of developing CAD than non-cancer patients (OR: 2.024, 95% CI: 1.475 to 2.778, p < 0.001). Respiratory (OR: 1.981, 95% CI: 1.236–3.175, p = 0.005), digestive (OR: 1.899, 95% CI: 1.177–3.064, p = 0.009) and urogenital (OR: 3.595, 95% CI: 1.696–7.620, p = 0.001) cancers were significantly associated with a higher risk of CAD compared with no cancer. (3) Patients with CAD also had a higher risk of developing cancer than non-CAD patients (OR = 2.157, 95% CI: 1.603 to 2.902, p < 0.001). Patients in the Alanine aminotransferase (ALT) level ≥ 40 U/L group had a lower risk of cancer than patients in the ALT level < 20 U/L group (OR: 0.490, 95% CI: 0.333–0.722, p < 0.001). (4) An integrated variable (Y = 0.205 × 10–1 age − 0.595 × 10–2 HGB − 0.116 × 10–1 ALT + 0.135 FIB) was identified for monitoring the occurrence of cancer among CAD patients, with an AUC of 0.720 and clinical sensitivity/specificity of 0.617/0.711.Conclusion(1) We discovered that CAD was an independent risk factor for cancer and vice versa. (2) Digestive, respiratory and urogenital cancers were independent risk factors for CAD. (3) We created a formula for the prediction of cancer among CAD patients. (4) ALT, usually considered a risk factor, was proven to be a protective factor for cancer in this study.

A Review on Role of Circadian Rhythms in Management of Prostate Cancer

The circadian clock is a molecular evolutionary mechanism that controls the time of physiology to maintain homeostasis. Circadian disorder in particular has been identified as an independent risk factor for cancer and has been classified as a carcinogen. The circadian rhythm regulates several biological pathways, including oncogenic tumors, metabolism, and cell reproduction. The new data examined in this article suggest that circadian regulatory functions play a key role in various aspects of cancer, including cell proliferation control, cell death, DNA repair, and metabolism. Circadian irregularities are incorrect input signals, such as exposure to night light, variability in circadian rhythm genes, and output changes that regulate circadian behavior, including melatonin. Night work, shift work, workday changes, urinary melatonin levels, and insomnia put older men at risk for prostate cancer. Melatonin has anti-cancer properties. Men with lower melatonin levels in the morning had a higher risk of advanced or fatal prostate cancer. Melatonin, a hormone found in the pineal gland, plays an important role in the functioning of the circadian function. The integration of circadian biology into cancer research opens up new avenues for more effective cancer treatment, including the prevention, diagnosis, and treatment of this destructive disease. This review examines the role of the circadian clock in tumor formation and cancer symptoms, and examines whether pharmacological changes in circadian clock genes may lead to new treatment options.

White Matter Integrity and Nicotine Dependence: Evaluating Vertical and Horizontal Pleiotropy.

Tobacco smoking is an addictive behavior that supports nicotine dependence and is an independent risk factor for cancer and other illnesses. Its neurogenetic mechanisms are not fully understood but may act through alterations in the cerebral white matter (WM). We hypothesized that the vertical pleiotropic pathways, where genetic variants influence a trait that in turn influences another trait, link genetic factors, integrity of cerebral WM, and nicotine addiction. We tested this hypothesis using individual genetic factors, WM integrity measured by fractional anisotropy (FA), and nicotine dependence-related smoking phenotypes, including smoking status (SS) and cigarettes per day (CPDs), in a large epidemiological sample collected by the UK Biobank. We performed a genome-wide association study (GWAS) to identify previously reported loci associated with smoking behavior. Smoking was found to be associated with reduced WM integrity in multiple brain regions. We then evaluated two competing vertical pathways: Genes → WM integrity → Smoking versus Genes → Smoking → WM integrity and a horizontal pleiotropy pathway where genetic factors independently affect both smoking and WM integrity. The causal pathway analysis identified 272 pleiotropic single-nucleotide polymorphisms (SNPs) whose effects on SS were mediated by FA, as well as 22 pleiotropic SNPs whose effects on FA were mediated by CPD. These SNPs were mainly located in important susceptibility genes for smoking-induced diseases NCAM1 and IREB2. Our findings revealed the role of cerebral WM in the maintenance of the complex addiction and provided potential genetic targets for future research in examining how changes in WM integrity contribute to the nicotine effects on the brain.

Cutaneous Malignancies After Kidney and Simultaneous Pancreas-Kidney Transplantations

Organ transplant recipients are at increased risk of nonmelanotic skin cancers (NMSC). Scarce data exist regarding secondary malignancies developing post-simultaneous pancreas-kidney (SPK) transplantations. Our aim was to assess long-term risk of skin cancers among kidney alone (KA) and SPK transplantation recipients. In this study, 521 patients who underwent KA or SPK transplantation at our medical center were observed up by dedicated nephrologists and dermatologists. SPK transplantation recipients were matched with a control group of KA transplantation recipients based on demographic and clinical data. A multivariate analysis was performed to find independent cancer risk factors. Patients who developed skin cancer were generally older, had a fair skin type, and had a higher incidence of NMSC before transplantation. Older age and fair skin type were independent risk factors on multivariate analysis. SPK transplantation in itself was not an independent risk factor. Cancer recurrence was associated with older age and male sex. Darker skin type and lowered immunosuppressive burden were protective. In contrast to previous studies, the use of antithymocytic agents or SPK transplantation were not independently associated with increased skin cancer risk in this multivariate analysis. These findings emphasize the complex interplay between posttransplantation NMSC and various clinical and epidemiologic risk parameters.

CIRCADIAN CLOCK AND ITS ROLE FOR INDUCING OR PREVENTING CANCER WITH A VIEW ON CHRONOTHERAPY FOR CANCER TREATMENT

The circadian clock is well known as a master regulator of mammalian physiology that regulates crucial biological processes in our body to maintain homeostasis and behaviors. We know that perturbation of the clock rhythmicity can change these crucial systems and can cause various diseases. In recent years, circadian rhythm disruption has been identified as an independent risk factor for cancer and thereby classified as a carcinogen. Different data showed circadian rhythm and clock genes to play very critical roles in several hallmarks for cancer, apoptosis, control of tumor cell proliferation, DNA repair, and metabolic alterations. In this review, we discussed the role of the circadian clock as a cause and in the management of cancer with several examples of studies that held great promise to use chronotherapy in standard clinical practice in the future. Nonetheless, a profound understanding on the molecular level regarding the factors of the clock that help or prevent cancer is still needed. The development of novel therapeutics targeting clock-mediated cancer-inducing factors is also needed to ensure the survival of cancer patients along with the existing chemotherapeutics. Keywords: Circadian Clock, Cancer, Clock genes, Chronotherapy.