Questions Swirl Around Screening for Multiple Cancers With a Single Blood Test.

This Medical News story discusses questions about multiple cancer early detection tests, 2 of which are already on the US market.

Priming agents transiently reduce the clearance of cell-free DNA to improve liquid biopsies.

Liquid biopsies enable early detection and monitoring of diseases such as cancer, but their sensitivity remains limited by the scarcity of analytes such as cell-free DNA (cfDNA) in blood. Improvements to sensitivity have primarily relied on enhancing sequencing technology ex vivo. We sought to transiently augment the level of circulating tumor DNA (ctDNA) in a blood draw by attenuating its clearance in vivo. We report two intravenous priming agents given 1 to 2 hours before a blood draw to recover more ctDNA. Our priming agents consist of nanoparticles that act on the cells responsible for cfDNA clearance and DNA-binding antibodies that protect cfDNA. In tumor-bearing mice, they greatly increase the recovery of ctDNA and improve the sensitivity for detecting small tumors.

Deploying blood-based cancer screening.

AI-based risk assessment may enable personalized blood-based multicancer screening.

The combination of soluble forms of PD-1 and PD-L1 as a predictive marker of PD-1 blockade in patients with advanced cancers: a multicenter retrospective study.

Introduction: The clinical relevance of soluble forms of programmed cell death-1 (sPD-1) and programmed cell death-ligand 1 (sPD-L1) remains unclear. We here investigated the relation between the efficacy of PD-1 blockade and pretreatment plasma levels of sPD-1 and sPD-L1 across a broad range of cancer types. Methods: We retrospectively analyzed clinical data from 171 patients with advanced solid tumors who received nivolumab or pembrolizumab monotherapy regardless of treatment line. The concentrations of sPD-1 and sPD-L1 were measured with a fully automated immunoassay (HISCL system). Results: The study subjects comprised patients with head and neck cancer (n = 50), urothelial cancer (n = 42), renal cell cancer (n = 37), gastric cancer (n = 20), esophageal cancer (n = 10), malignant pleural mesothelioma (n = 6), or microsatellite instability-high tumors (n = 6). High or low levels of sPD-1 or sPD-L1 were not significantly associated with progression-free survival (PFS) or overall survival (OS) for PD-1 blockade in the entire study population. Comparison of treatment outcomes according to combinations of high or low sPD-1 and sPD-L1 levels, however, revealed that patients with low sPD-1 and high sPD-L1 concentrations had a significantly poorer PFS (HR of 1.79 [95% CI, 1.13-2.83], p = 0.01) and a tendency toward poorer OS (HR of 1.70 [95% CI, 0.99-2.91], p = 0.05) compared with all other patients. Conclusion: Our findings suggest that the combination of low sPD-1 and high sPD-L1 levels is a potential negative biomarker for PD-1 blockade therapy.

Nivel de hemoglobina y fuerza de prensión manual en pacientes oncológicos adultos de un hospital público / Hemoglobin level and handgrip strength deficit in adult cancer patients from a public hospital

Introducción: La anemia en el adulto se caracteriza por ladebilidad y cansancio e influye en el aumento de tasa de mortalidad, discapacidad, disminución en el nivel de actividad física y calidad de vida. Condición que agrava el riesgo de mortalidad en pacientes oncológicos. Objetivo: Determinar la correlación entre el nivel de he-moglobina y la fuerza de prensión manual en pacientes oncológicos de un hospital público. Materiales y métodos: Investigación de enfoque cuanti ta-tivo, diseño no experimental, transversal de tipo correla cional-causal. La muestra final del estudio estuvo conformada por 90pacientes adultos con diagnóstico de enfermedad oncológica; hospitalizados durante el periodo noviembre a diciembre del2022, en el servicio de cirugía del Hospital Cayetano Heredia deLima-Perú. La fuerza de prensión manual se determinó utili-zando un dinamómetro hidráulico y los valores de hemoglobinase recabaron de la historia clínica del paciente al ingreso al hospital. Para evaluar la correlación de las variables, se utilizó laprueba estadística no paramé trica RHO de Spearman. Resultados: El 51,1% presentó anemia moderada, el16.7% anemia leve y el 31.1% presentó un valor de hemoglobina normal. Asimismo, el 53.3% presentó una fuerza deprensión manual disminuida. Al determinar la correlación entre el nivel de hemoglobina y el déficit de fuerza de prensiónmanual en pacientes oncológicos adultos se obtuvo un valorde Rho = 0.274 y p=0.009 (p<0.05). Conclusiones: Existe correlación directa entre nivel de hemoglobina y la fuerza de prensión manual. Los pacientes oncológicos adultos con mayor valor de hemoglobina presenta-ron mayor fuerza de prensión manual (AU)

Introduction: Anemia in adults is characterized by weakness and tiredness and influences the increase in the mortality rate, disability, decrease in the level of physical activity andquality of life, a condition that aggravates the risk of mortality in cancer patients. Objective: To determine the correlation between the he-moglobin level and the handgrip strength in cancer patients from a public hospital. Materials and methods: Research with a quantitative approach, non-experimental, cross-sectional design of a cor-relational-causal type. The final sample of the study consistedof 90 adult patients diagnosed with oncological disease, hospitalized from November to December 2022, in the surgery service of the Cayetano Heredia Hospital in Lima-Peru. Handgrip strength was determined using a hydraulic dynamometer, and hemoglobin values were collected from the patient’s medical history upon admission to the hospital. Forthe correlation of the variables, the non-parametric statisticaltest Spearman’s Rho was used. Results: 51.1% presented moderate anemia, 16.7% mild anemia and 31.1% presented a normal hemoglobin value. Likewise, 53.3% presented a decreased handgrip strength. When determining the correlation between the hemoglobin level and the handgrip strength deficit in adult cancer patients, a value of Rho = 0.274 and p=0.009 (p<0.05). Conclusions: There is a direct correlation between hemoglobin level and handgrip strength. Adult cancer patients with higher hemoglobin values presented greater handgrip strength (AU)

Increased plasma DR-70 (fibrinogen-fibrin degradation products) concentrations as a diagnostic biomarker in dogs with neoplasms.

BACKGROUND: Tumor biomarkers have used widely in clinical oncology in human medicine. Only a few studies have evaluated the clinical utility of tumor biomarkers for veterinary medicine. A test for fibrinogen and fibrin degradation products (DR-70) has been proposed as an ideal biomarker for tumors in humans. The clinical value of DR-70 for veterinary medicine however has yet to be determined. OBJECTIVES: Investigate the diagnostic value of DR-70 concentrations by comparing them between healthy dogs and dogs with tumors. ANIMALS: Two hundred sixty-three dogs with different types of tumors were included. Sixty healthy dogs also were recruited for comparison. METHODS: The DR-70 concentrations were measured in all recruited individuals by ELISA. Clinical conditions were categorized based on histopathology, cytology, ultrasound examination, radiology, clinical findings, and a combination of these tests. RESULTS: The median concentration of DR-70 was 2.130 ± 0.868 µg/mL in dogs with tumors, which was significantly higher than in healthy dogs (1.202 ± 0.610 µg/mL; P < .0001). With a cut-off of 1.514 µg/mL, the sensitivity and specificity of DR-70 were 84.03% and 78.33%, respectively. The area under curve was 0.883. The DR-70 concentration can be an effective tumor biomarker in veterinary medicine. CONCLUSIONS AND CLINICAL IMPORTANCE: Increased DR-70 concentrations were not affected by tumor type, sex, age, or body weight. However, in dogs with metastatic mast cell tumors and oral malignant melanoma, DR-70 concentrations were significantly increased. Additional studies, including more dogs with nonneoplastic diseases, are needed to further evaluate the usefulness of DR-70 as a tumor biomarker.

Multimodal analysis of methylomics and fragmentomics in plasma cell-free DNA for multi-cancer early detection and localization.

Despite their promise, circulating tumor DNA (ctDNA)-based assays for multi-cancer early detection face challenges in test performance, due mostly to the limited abundance of ctDNA and its inherent variability. To address these challenges, published assays to date demanded a very high-depth sequencing, resulting in an elevated price of test. Herein, we developed a multimodal assay called SPOT-MAS (screening for the presence of tumor by methylation and size) to simultaneously profile methylomics, fragmentomics, copy number, and end motifs in a single workflow using targeted and shallow genome-wide sequencing (~0.55×) of cell-free DNA. We applied SPOT-MAS to 738 non-metastatic patients with breast, colorectal, gastric, lung, and liver cancer, and 1550 healthy controls. We then employed machine learning to extract multiple cancer and tissue-specific signatures for detecting and locating cancer. SPOT-MAS successfully detected the five cancer types with a sensitivity of 72.4% at 97.0% specificity. The sensitivities for detecting early-stage cancers were 73.9% and 62.3% for stages I and II, respectively, increasing to 88.3% for non-metastatic stage IIIA. For tumor-of-origin, our assay achieved an accuracy of 0.7. Our study demonstrates comparable performance to other ctDNA-based assays while requiring significantly lower sequencing depth, making it economically feasible for population-wide screening.

Unveiling the diagnostic enigma of D-dimer testing in cancer patients: Current evidence and areas of application.

BACKGROUND: Cancer is a well-known risk factor for venous thromboembolism (VTE). A combined strategy of D-dimer testing and clinical pre-test probability is usually used to exclude VTE. However, its effectiveness is diminished in cancer patients due to reduced specificity, ultimately leading to a decreased clinical utility. This review article seeks to provide a comprehensive summary of how to interpret D-dimer testing in cancer patients. METHODS: In accordance with PRISMA standards, literature pertaining to the diagnostic and prognostic significance of D-dimer testing in cancer patients was carefully chosen from reputable sources such as PubMed and the Cochrane databases. RESULTS: D-dimers have not only a diagnostic value in ruling out VTE but can also serve as an aid for rule-in if their values exceed 10-times the upper limit of normal. This threshold allows a diagnosis of VTE in cancer patients with a positive predictive value of more than 80%. Moreover, elevated D-dimers carry important prognostic information and are associated with VTE reoccurrence. A gradual increase in risk for all-cause death suggests that VTE is also an indicator of biologically more aggressive cancer types and advanced cancer stages. Considering the lack of standardization for D-dimer assays, it is essential for clinicians to carefully consider the variations in assay performance and the specific test characteristics of their institution. CONCLUSIONS: Standardizing D-dimer assays and developing modified pretest probability models specifically for cancer patients, along with adjusted cut-off values for D-dimer testing, could significantly enhance the accuracy and effectiveness of VTE diagnosis in this population.

Serum 25-hydroxyvitamin D concentrations are inversely associated with all-cause mortality among Koreans: a nationwide cohort study.

Evidence on the association between serum 25-hydroxyvitamin D (25(OH)D) concentration and all-cause and cause-specific mortality in Asians, especially Koreans, is limited. We hypothesized that high concentrations of 25(OH)D are associated with lower all-cause and cause-specific mortality in the general Korean population. This study included 27,846 adults participating in the Fourth and Fifth Korean National Health and Nutrition Examination Survey 2008-2012, followed up through December 31, 2019. Hazard ratios (HR) and 95% confidence intervals (CIs) for mortality from all causes, cardiovascular disease (CVD), and cancer were estimated using multivariable-adjusted Cox proportional hazards regression. The weighted mean serum 25(OH)D of study participants was 17.77 ng/mL; 66.5% had vitamin D deficiency (<20 ng/mL) and 94.2% had insufficient vitamin D (<30 ng/mL). During a median follow-up of 9.4 years (interquartile range, 8.1-10.6 years), 1680 deaths were documented, including 362 CVD deaths and 570 cancer deaths. Serum 25(OH)D levels ≥30 ng/mL were inversely associated with all-cause mortality (HR, 0.57; 95% CI, 0.43-0.75) compared with serum 25(OH)D levels <10 ng/mL. Based on the quartile cutoffs of serum 25(OH)D concentration, the highest quartile of serum 25(OH)D concentration (≥21.8 ng/mL) was associated with the lowest all-cause mortality (HR, 0.72; 95% CI, 0.60-0.85; P trend < .001), and CVD mortality (HR, 0.60; 95% CI, 0.42-0.85; P trend = .006). No association with cancer mortality outcome was found. In conclusion, higher serum 25(OH)D levels were associated with lower all-cause mortality in the general Korean population. An additional association was found between higher quartile of serum 25(OH)D and lower CVD mortality.

The next big questions in cancer research.

Our understanding of tumorigenesis and cancer progression as well as clinical therapies for different cancer types have evolved dramatically in recent years. However, even with this progress, there are big challenges for scientists and oncologists to tackle, ranging from unpacking the molecular and cellular mechanisms involved to therapeutics and biomarker development to quality of life in the aftermath of therapy. In this article, we asked researchers to comment on the questions that they think are important to address in the coming years.

Serum Copeptin in Cardiooncology Practice: Review of Pathophysiological and Clinical Implications.

In cardiooncology practice, "early cardiotoxicity" refers to an emerging subclinical myocardial dysfunction/injury in response to certain chemotherapeutic regimens. This condition can progress to overt cardiotoxicity in time and hence warrants proper and timely diagnostic and preventive strategies. Current diagnostic strategies for "early cardiotoxicity" are largely based on conventional biomarkers and certain echocardiographic indices. However, a significant gap still exists in this setting, warranting further strategies to improve diagnosis and overall prognosis in cancer survivors. Copeptin (surrogate marker of the arginine vasopressine axis) might serve as a promising adjunctive guide for the timely detection, risk stratification, and management of early cardiotoxicity on top of conventional strategies largely due to its multifaceted pathophysiological implications in the clinical setting. This work aims to focus on serum copeptin as a marker of "early cardiotoxicity" and its general clinical implications in patients with cancer.

Circulating microRNAs as Reliable Tumor Biomarkers: Opportunities and Challenges Facing Clinical Application.

MicroRNAs (miRNAs) are involved in the development of human malignancies, and cells have the ability to secrete these molecules into extracellular compartments. Thus, cell-free miRNAs (circulating miRNAs) can potentially be used as biomarkers to evaluate pathophysiological changes. Although circulating miRNAs have been proposed as potential noninvasive tumor biomarkers for diagnosis, prognosis, and response to therapy, their routine application in the clinic is far from being achieved. This review focuses on the recent progress regarding the value of circulating miRNAs as noninvasive biomarkers, with specific consideration of their relevant clinical applications. In addition, we provide an in-depth analysis of the technical challenges that impact the assessment of circulating miRNAs. We also highlight the significance of integrating circulating miRNAs with the standard laboratory biomarkers to boost sensitivity and specificity. The current status of circulating miRNAs in clinical trials as tumor biomarkers is also covered. These insights and general guidelines will assist researchers in experimental practice to ensure quality standards and repeatability, thus improving future studies on circulating miRNAs. SIGNIFICANCE STATEMENT: Our review will boost the knowledge behind the inconsistencies and contradictory results observed among studies investigating circulating miRNAs. It will also provide a solid platform for better-planned strategies and standardized techniques to optimize the assessment of circulating cell-free miRNAs.

Hypercalcemia: A Review.

Importance: Hypercalcemia affects approximately 1% of the worldwide population. Mild hypercalcemia, defined as total calcium of less than 12 mg/dL (<3 mmol/L) or ionized calcium of 5.6 to 8.0 mg/dL (1.4-2 mmol/L), is usually asymptomatic but may be associated with constitutional symptoms such as fatigue and constipation in approximately 20% of people. Hypercalcemia that is severe, defined as total calcium of 14 mg/dL or greater (>3.5 mmol/L) or ionized calcium of 10 mg/dL or greater (≥2.5 mmol/L) or that develops rapidly over days to weeks, can cause nausea, vomiting, dehydration, confusion, somnolence, and coma. Observations: Approximately 90% of people with hypercalcemia have primary hyperparathyroidism (PHPT) or malignancy. Additional causes of hypercalcemia include granulomatous disease such as sarcoidosis, endocrinopathies such as thyroid disease, immobilization, genetic disorders, and medications such as thiazide diuretics and supplements such as calcium, vitamin D, or vitamin A. Hypercalcemia has been associated with sodium-glucose cotransporter 2 protein inhibitors, immune checkpoint inhibitors, denosumab discontinuation, SARS-CoV-2, ketogenic diets, and extreme exercise, but these account for less than 1% of causes. Serum intact parathyroid hormone (PTH), the most important initial test to evaluate hypercalcemia, distinguishes PTH-dependent from PTH-independent causes. In a patient with hypercalcemia, an elevated or normal PTH concentration is consistent with PHPT, while a suppressed PTH level (<20 pg/mL depending on assay) indicates another cause. Mild hypercalcemia usually does not need acute intervention. If due to PHPT, parathyroidectomy may be considered depending on age, serum calcium level, and kidney or skeletal involvement. In patients older than 50 years with serum calcium levels less than 1 mg above the upper normal limit and no evidence of skeletal or kidney disease, observation may be appropriate. Initial therapy of symptomatic or severe hypercalcemia consists of hydration and intravenous bisphosphonates, such as zoledronic acid or pamidronate. In patients with kidney failure, denosumab and dialysis may be indicated. Glucocorticoids may be used as primary treatment when hypercalcemia is due to excessive intestinal calcium absorption (vitamin D intoxication, granulomatous disorders, some lymphomas). Treatment reduces serum calcium and improves symptoms, at least transiently. The underlying cause of hypercalcemia should be identified and treated. The prognosis for asymptomatic PHPT is excellent with either medical or surgical management. Hypercalcemia of malignancy is associated with poor survival. Conclusions and Relevance: Mild hypercalcemia is typically asymptomatic, while severe hypercalcemia is associated with nausea, vomiting, dehydration, confusion, somnolence, and coma. Asymptomatic hypercalcemia due to primary hyperparathyroidism is managed with parathyroidectomy or observation with monitoring, while severe hypercalcemia is typically treated with hydration and intravenous bisphosphonates.

Dampened Inflammatory Signalling and Myeloid-Derived Suppressor-Like Cell Accumulation Reduces Circulating Monocytic HLA-DR Density and May Associate With Malignancy Risk in Long-Term Renal Transplant Recipients.

Background: Malignancy is a major cause of morbidity and mortality in transplant recipients. Identification of those at highest risk could facilitate pre-emptive intervention such as reduction of immunosuppression. Reduced circulating monocytic HLA-DR density is a marker of immune depression in the general population and associates with poorer outcome in critical illness. It has recently been used as a safety marker in adoptive cell therapy trials in renal transplantation. Despite its potential as a marker of dampened immune responses, factors that impact upon monocytic HLA-DR density and the long-term clinical sequelae of this have not been assessed in transplant recipients. Methods: A cohort study of stable long-term renal transplant recipients was undertaken. Serial circulating monocytic HLA-DR density and other leucocyte populations were quantified by flow cytometry. Gene expression of monocytes was performed using the Nanostring nCounter platform, and 13-plex cytokine bead array used to quantify serum concentrations. The primary outcome was malignancy development during one-year follow-up. Risk of malignancy was calculated by univariate and multivariate proportionate hazards modelling with and without adjustment for competing risks. Results: Monocytic HLA-DR density was stable in long-term renal transplant recipients (n=135) and similar to non-immunosuppressed controls (n=29), though was suppressed in recipients receiving prednisolone. Decreased mHLA-DRd was associated with accumulation of CD14+CD11b+CD33+HLA-DRlo monocytic myeloid-derived suppressor-like cells. Pathway analysis revealed downregulation of pathways relating to cytokine and chemokine signalling in monocytes with low HLA-DR density; however serum concentrations of major cytokines did not differ between these groups. There was an independent increase in malignancy risk during follow-up with decreased HLA-DR density. Conclusions: Dampened chemokine and cytokine signalling drives a stable reduction in monocytic HLA-DR density in long-term transplant recipients and associates with subsequent malignancy risk. This may function as a novel marker of excess immunosuppression. Further study is needed to understand the mechanism behind this association.

Circulating exosomal miRNAs and cancer early diagnosis

Microribonucleic acids (miRNAs) are small non-coding ribonucleic acids (ncRNAs), which can affect recognition of homologous sequences and interfere with transcription. It plays key roles in the initiation, development, resistance, metastasis or recurrence of cancers. Identifying circulatory indicators will positively improve the prognosis and quality of life of patients with early cancer. Previous studies have shown that miRNA is highly involved in cancer. In addition, miRNA derived from cancers can be encapsulated as exosomes and further extracted into circulatory systems to realize malignant functions. It indicates that circulating exosome-derived miRNAs have the potential to replace conventional biomarkers as cancer derived exosomes carrying miRNAs can be identified by specific markers and might be more stable and accurate for early diagnosis.

Serologic response following SARS-COV2 vaccination in patients with cancer: a systematic review and meta-analysis.

PURPOSE: Patients with cancer have an increased risk of coronavirus disease 2019 (COVID-19) and an attenuated responses to various vaccines. This meta-analysis aims to assess the serologic response to COVID-19 vaccination in patients with cancer. METHODS: Electronic databases were systematically searched on August 1, 2021 for studies that reported the serologic response to COVID-19 vaccine in cancer patients. Random effects models were used to achieve pooled serologic response rates and odds ratios (ORs). RESULTS: We analyzed 16 observational studies with a total of 1453 patients with cancer. A majority of studies used mRNA vaccines (BNT162b2 or mRNA-1273). The proportion of patients achieving a serologic response after a single and two doses of COVID-19 vaccine were 54.2% (95% confidence interval [CI] 41.0-66.9) and 87.7% (95% CI 82.5-91.5), respectively. Patients with hematologic cancers had a lower response rate after the second dose of vaccine compared to those with solid organ cancers (63.7% vs. 94.9%), which was attributable to the low response rates associated with certain conditions (chronic lymphocytic leukemia, lymphoma) and therapies (anti-CD20, kinase inhibitors). A lower proportion of patients with cancer achieved a serologic response compared to control patients after one and two doses of vaccine (OR0.073 [95% CI 0.026-0.20] and 0.10 [95% CI 0.039-0.26], respectively). CONCLUSIONS: Patients with cancer, especially those with hematologic B-cell malignancies, have a lower serologic response to COVID-19 vaccines. The results suggest that cancer patients should continue to follow safety measures including mask-wearing after vaccination and suggest the need for additional strategies for prophylaxis.

The blood urea nitrogen/creatinine (BUN/cre) ratio was U-shaped associated with all-cause mortality in general population.

OBJECTIVES: This study aimed to explore the relationship between the blood urea nitrogen/creatinine (BUN/Cre) ratio and all-cause or cause-specific mortality in the general population. METHODS: Participants were enrolled from the National Health and Nutrition Examination Survey (NHANES) during 1999 to 2014. Baseline variables were acquired from questionnaires and examinations. Death status were ascertained from National Death Index records. Cox proportional hazards models with cubic spines were used to estimate hazard ratios (HRs) and 95% confidence interval (CI) of all-cause mortality, cardiovascular and cancer mortality. RESULTS: A total of 42038 participants were enrolled in the study with a median 8.13 years of follow-up. Older people and women tend to have a higher BUN/Cre ratio. After multivariable adjustment, BUN/Cre ratio between 11.43 and 14.64 was associated with the lowest all-cause mortality compared with the participants with the lowest quartile (HR 0.83 [0.76, 0.91]; p < 0.001). The highest quartile of BUN/Cre ratio was associated with the lowest risk of cancer mortality (HR 0.64 [0.53, 0.78]; p < 0.001). Restricted cubic splines showed BUN/Cre was nonlinearly associated with all-cause mortality and linearly associated with cancer mortality. CONCLUSIONS: This study confirmed a U-shape relationship between BUN/Cre ratio and all-cause mortality in the general population.

Stimuli-Mediated Specific Isolation of Exosomes from Blood Plasma for High-Throughput Profiling of Cancer Biomarkers.

Exosomes, ranging from 30-150 nm in diameter, have emerged as promising non-invasive biomarkers for the diagnosis and prognosis of numerous diseases. However, current research on exosomes is largely restricted by the lack of an efficient method to isolate exosomes from real samples. Herein, the first stimuli-mediated enrichment and purification system to selectively and efficiently extract exosomes from clinical plasma for high-throughput profiling of exosomal mRNAs as cancer biomarkers is presented. This novel isolation system relies on specific installation of the stimuli-responsive copolymers onto exosomal phospholipid bilayers, by which the enrichment and purification are exclusively achieved for exosomes rather than the non-vesicle counterparts co-existing in real samples. The stimuli-mediated isolation system outperforms conventional methods such as ultracentrifugation and polyethylene glycol-based precipitation in terms of isolation yield, purity, and retained bioactivity. The high performance of the isolation system is demonstrated by enriching exosomes from 77 blood plasma samples and validated the clinical potentials in profiling exosomal mRNAs for cancer diagnosis and discrimination with high accuracy. This simple isolation system can boost the development of extracellular vesicle research, not limited to exosomes, in both basic and clinical settings.

Analysis of Platelet Count and New Cancer Diagnosis Over a 10-Year Period.

Importance: Individuals with cancer often have an elevated platelet count at the time of diagnosis. The extent to which an elevated platelet count is an indicator of cancer is unclear. Objective: To evaluate the association of an elevated platelet count with a cancer diagnosis. Design, Setting, and Participants: This nested case-control study included Ontario residents enrolled in the provincial health insurance plan who had 1 or more routine complete blood count (CBC) tests performed between January 1, 2007, and December 31, 2017, with follow-up through December 31, 2018. Case patients were individuals with a new cancer diagnosis during the observation period. Eligible control individuals were cancer free before the date of diagnosis for a case patient to whom they were matched. One case patient was matched to 3 controls based on sex, age, and health care use patterns. Data were analyzed from September 24, 2020, to July 13, 2021. Exposures: Case patients and controls were assigned to 1 of 5 exposure groups based on age- and sex-specific platelet count distributions in the control population: very low (≤10th percentile), low (>10th to 25th percentile), medium (>25th to <75th percentile), high (75th to <90th percentile), and very high (≥90th percentile). Main Outcomes and Measures: Odds ratios (ORs) were estimated for specific cancer sites for each category of platelet count at intervals up to 10 years after a blood test. Results: Of the 8 917 187 eligible Ontario residents with a routine CBC record available, 4 971 578 (55.8%) were women; the median age at the first CBC was 46.4 years (IQR, 32.5-59.5 years). Among individuals with a routine CBC record available, 495 341 (5.6%) received a diagnosis of first primary cancer during the 10-year observation period. The OR for a solid tumor diagnosis associated with a very high platelet count vs a medium platelet count in the 6-month period before the diagnosis was 2.32 (95% CI, 2.28-2.35). A very high platelet count was associated with colon (OR, 4.38; 95% CI, 4.22-4.54), lung (OR, 4.37; 95% CI, 4.22-4.53), ovarian (OR, 4.62; 95% CI, 4.19-5.09), and stomach (OR, 4.27; 95% CI, 3.91-4.66) cancers. Odds ratios attenuated with increasing time from CBC test to cancer diagnosis. Conclusions and Relevance: In this nested case-control study, an elevated platelet count was associated with increased risk of cancer at several sites. Our findings suggest that an elevated platelet count could potentially serve as a marker for the presence of some cancer types.

Spontaneous Chromosomal Aberrations in Lymphocytes and Development of Tumor in Hospital Workers.

BACKGROUND: Cytogenetic analysis of chromosomes in blood lymphocytes can be used to reveal biomarkers of tumor risk. The frequency of chromosomal aberrations (CAs) appears to correlate with the later incidence of cancer. PATIENTS AND METHODS: In our work, a total of 515 healthy Hungarian medical workers and 725 controls were enrolled in our investigation. The CAs in peripheral blood lymphocytes were analyzed. RESULTS: The frequency of CAs was significantly higher in the groups working with ionizing radiation and with cytostatic agents compared to unexposed controls and in male smokers rather than non-smokers. The frequency of dicentric chromosomes, however, was not significantly different between control and exposed groups. Among 82 cancer cases (6.6%), the most frequent types were cancer of the breast (20.5%), colon (12.8%), lung and thyroid gland (9-9%). Our analysis showed 8.1% cancer cases in smokers compared to 5.7% in non-smokers. CONCLUSION: The potential exposure to carcinogens did not modify the effect of CAs on cancer risk but tobacco smoking did increase risk.