Cancer Mortality Research Articles

CDR1as/miR-7-5p/IGF1R axis contributes to the suppression of cell viability in prostate cancer

Abstract Background Prostate cancer is the most frequently diagnosed male cancer and the fifth highest cause of cancer mortality in men. CDR1as has played an essential role in the growth of several malignancies. However, its significance in the progression of prostate cancer has not been investigated. We aimed to investigate the role and mechanism of CDR1as in the development of prostate cancer and identify a new target for diagnostics and treatment. Methods CDR1as siRNA and miR-7-5p mimic were transfected into PC3 and DU145 PCa cell lines and their effects on cellular processes were investigated. Cell viability was measured by WST-8 assay. The role of CDR1as and/or miR-7-5p on PCa cell migration was detected using the scratch-wound assay. The apoptotic capacity of the cells was evaluated using the Caspase-3 kit. The potential targets of miR-7-5p were defined via in silico tools. mRNA and protein expression levels of IGF1R and EIF4E were detected by qRT-PCR and western blot assays, respectively. The matching between miR-7-5p and IGF1R was defined via luciferase reporter assay. Results Inhibiting CDR1as or restoring miR-7-5p reduced prostate cancer cell proliferation and migration while increasing apoptosis. Silencing CDR1as elevated the expression of miR-7-5p while decreasing IGF1R. Conclusions CDR1as functions as a miR-7-5p sponge, increasing IGF1R expression and promoting tumor development.

The Association Between Perioperative Red Blood Cell Transfusions and 1-Year Mortality After Major Cancer Surgery: An International Multicenter Observational Study.

Packed red blood cell (pRBC) transfusions in patients undergoing surgery for cancer are given to treat anemia or acute hemorrhage. Evidence indicates that pRBC transfusions are associated with poor perioperative and oncological outcomes. The ARCA-1 (Perioperative Care in the Cancer Patient-1) study was designed to test the association between perioperative pRBC transfusions and postoperative morbidity and mortality in patients undergoing cancer surgery. The primary hypothesis of our study was that perioperative pRBC transfusions have a negative impact on postoperative morbidity and 1-year mortality. ARCA-1 was an international multicenter prospective observational cohort study. Participating centers enrolled a minimum of 30 consecutive adult patients with cancer who underwent surgery with curative intent. The primary end point was all-cause mortality 1 year after major cancer surgery. Secondary end points were rates of perioperative blood product use, 1-year cancer-specific mortality, overall survival, and 30-day morbidity and mortality. We performed a propensity score matching analysis to adjust for selection bias. A multivariable logistic regression model was fitted to estimate the effects of significant covariates on 1-year mortality, cancer-related mortality, and overall survival. A total of 1079 patients were included in the study. The rate of perioperative pRBC transfusions was 21.1%. Preoperative comorbidities, including anemia, American Society of Anesthesiologists (ASA) score of III to IV, a history of coronavirus disease 2019 (COVID-19), myocardial infarction, stroke, need for dialysis, history of blood transfusions, and metastatic disease were statistically significantly more frequent in transfused patients compared to nontransfused patients. The 1-year mortality rate was higher in transfused patients before (19.7% vs 6.5%; P < .0001) and after (17.4% vs 13.2%; P = .29) propensity score matching. 1-year mortality was 1.97 times higher in transfused than in no-transfused patients (odd ratio [OR], 1.97; 95% confidence interval [CI], 1.13-3.41). The odds of 1-year cancer mortality for patients who had perioperative pRBCs was 1.82 times higher (OR, 1.82; 95% CI, 0.97-3.43) compared to those who did not receive perioperative pRBC transfusion. The effect of perioperative pRBC transfusion on overall survival was also significant (hazard ratio [HR], 1.85; 95% CI, 1.15-2.99). Transfused patients also had a higher rate of 30-day postoperative mortality before (3.5% vs 0.7%; P = .0009) and after propensity score matching (4.2% vs 1.8%; P = .34). This international, multicenter observational study showed that perioperative pRBC transfusion was associated with an increased mortality risk.

The Diverse Aspects of Uterine Serous Cancer: An NCI workshop on the status of and opportunities for advancement of research.

The marked increase in incidence and mortality in endometrial cancer over the last two decades is driven in part by rising rates of higher grade, more aggressive endometrial cancers with mutations in TP53, uterine serous cancers and their dedifferentiated component, uterine carcinosarcomas (collectively USC). USC rates have been increasing among all racial and ethnic groups, with higher rates of this aggressive uterine cancer in Black women. The National Cancer Institute (NCI) hosted a workshop in June 2023 to examine the diverse aspects of USC across epidemiology, biology, and molecular genetics, and to advance knowledge from basic to preclinical and translational efforts. Key stakeholders came together including basic scientists, clinical investigators, and patient advocates to identify critical research gaps that, when addressed, would facilitate more comprehensive and rapid progress in understanding and ultimately treating USC across all patients. NCI released a supplemental funding opportunity (NOT-CA-24-044) in Spring 2024 to facilitate rapid translation of these recommendations.

Changes in Staging and Management of Non-Small Cell Lung Cancer (NSCLC) Patients Following the Implementation of Low-Dose Chest Computed Tomography (LDCT) Screening at Kaohsiung Medical University Hospital

Background: Low-dose computed tomography (LDCT) has been widely adopted for lung cancer screening due to its proven ability to reduce lung cancer mortality, especially among high-risk populations. Methods: This retrospective study aims to evaluate the impact of LDCT screening on non-small cell lung cancer (NSCLC) staging at Kaohsiung Medical University Hospital (KMUH) from 2011 to 2020, following the introduction of LDCT in 2013. The study examines the correlation between LDCT screening volume and changes in the distribution of NSCLC stages, particularly early-stage (stages 0 and I) and late-stage (stage IV) diagnoses. Additionally, it explores the differences in histopathological subtypes, focusing on adenocarcinoma and squamous cell carcinoma, and assesses the impact of early detection on five-year survival rates. Results: The results show a significant increase in early-stage NSCLC diagnoses, particularly in adenocarcinoma cases, where early-stage diagnoses rose from 10.4% in 2010 to 38.7% in 2019. However, the number of stage IV cases remained stable, indicating that LDCT may not substantially reduce late-stage diagnoses. Pearson’s correlation analysis demonstrated a strong positive correlation between LDCT screening and early-stage NSCLC detection, particularly for adenocarcinoma (p &lt; 0.001), though the early detection of squamous cell carcinoma and small cell carcinoma remained limited. Conclusions: The study concludes that LDCT screening plays a crucial role in improving early NSCLC detection and five-year survival rates. Future research should focus on optimizing screening strategies to capture more at-risk populations and enhance the detection of harder-to-diagnose subtypes like squamous cell carcinoma.

A deep learning approach for gastroscopic manifestation recognition based on Kyoto Gastritis Score.

The risk of gastric cancer can be predicted by gastroscopic manifestation recognition and the Kyoto Gastritis Score. This study aims to validate the applicability of AI approaches for recognizing gastroscopic manifestations according to the definition of Kyoto Gastritis Score, with the goal of improving early gastric cancer detection and reducing gastric cancer mortality. In this retrospective study, 29013 gastric endoscopy images were collected and carefully annotated into five categories according to the Kyoto Gastritis Score, i.e. atrophy (A), diffuse redness (DR), enlarged folds (H), intestinal metaplasia (IM), and nodularity (N). As a multi-label recognition task, we propose a deep learning approach composed of five GAM-EfficientNet models, each performing a multiple classification to quantify gastroscopic manifestations, i.e. no presentation or the severity score 0-2. This approach was compared with endoscopists of varying years of experience in terms of accuracy, specificity, precision, recall, and F1 score. The approach demonstrated good performance in identifying the five manifestations of the Kyoto Gastritis Score, with an average accuracy, specificity, precision, recall, and F1 score of 78.70%, 91.92%, 80.23%, 78.70%, and 0.78, respectively. The average performance of five experienced endoscopists was 72.63%, 90.00%, 77.68%, 72.63%, and 0.73, while that of five less experienced endoscopists was 66.60%, 87.44%, 70.88%, 66.60%, and 0.66, respectively. The sample t-test indicates that the approach's average accuracy, specificity, precision, recall, and F1 score for identifying the five manifestations were significantly higher than those of less experienced endoscopists, experienced endoscopists, and all endoscopists on average (p < 0.05). Our study demonstrates the potential of deep learning approaches on gastric manifestation recognition over junior, even senior endoscopists. Thus, the deep learning approach holds potential as an auxiliary tool, although prospective validation is still needed to assess its clinical applicability.

Associations of saccharin intake with all-cause, cardiovascular and cancer mortality risk in USA adults.

Saccharin is a widely used sugar substitute, but little is known about the long-term health effects of saccharin intake. Our study aimed to examine the association between saccharin intake and mortality in diabetic and pre-diabetic population and overweight population from NHANES 1988-1994. Cox proportional hazard models were used to evaluate the association between saccharin intake and CVD, cancer and all-cause mortality. After multivariable adjustment, increased absolute saccharin intake was associated with the risk of all-cause mortality (hazard ratio (HR): 1·41, 95 % CI: 1·05, 1·90), CVD mortality (HR: 1·93, 95 % CI: 1·15, 3·25) and cancer mortality (HR: 2·26, 95 % CI: 1·10, 4·45) in diabetic and pre-diabetic population. Among overweight population, higher absolute saccharin intake was associated with the risk of cancer mortality (HR: 7·369, 95 % CI: 2·122, 25·592). Replacing absolute saccharin intake with total sugar significantly reduced all-cause mortality by 12·5 % and CVD mortality by 49·7 % in an equivalent substitution analysis in the diabetic and pre-diabetic population. Aspartame substitution reduced all-cause mortality by 29·2 % and cancer mortality by 30·2 %. Notably, the relative daily intake of saccharin also had similar effects as the absolute intake on all-cause, cardiovascular and cancer mortality in all analyses. This was despite the fact that the relative daily intake in our study was below the Food and Drug Administration limit of 15 mg/kg. In conclusion, our study showed a considerable risk of increased saccharin intake on the all-cause, CVD mortality and cancer mortality.

US Cancer Mortality Trends Among Asian and Pacific Islander Populations

Cancer is the leading cause of death among Asian American individuals and the second leading cause of death among Native Hawaiian and Pacific Islander people. To evaluate longitudinal cancer mortality trends from 1999 to 2020 among Asian American and Pacific Islander populations in the US by demographic characteristics. This cross-sectional study used the Centers for Disease Control and Prevention Wide-Ranging Online Data for Epidemiologic Research database to obtain age-adjusted cancer death rates among Asian American and Pacific Islander individuals of all ages between January 1, 1999, and December 31, 2020. Data were analyzed from January 12 to March 19, 2024. Age, sex, cancer type, and US census regions. Trends and average annual percent changes (AAPCs) in age-adjusted cancer-specific mortality (CSM) rates for non-Hispanic Asian American and Pacific Islander populations were estimated by cancer type, age, sex, and region using Joinpoint regression. Between 1999 and 2020, 305 386 Asian American and Pacific Islander individuals (median [IQR] age, 69.5 [58.5-79.2] years; 51.1% male) died of cancer in the US. Overall, the CSM rate decreased by 1.5% annually. Men experienced a greater CSM rate decrease (AAPC, -1.8%; 95% CI, -2.2% to -1.3%) compared with women (AAPC, -1.1%; 95% CI: -1.2% to -1.0%). For women, death rates decreased for most cancer types but increased for uterine (AAPC, 2.5%; 95% CI, 2.0%-3.0%) and brain and central nervous system (AAPC, 1.4%; 95% CI: 0.7%-2.1%) cancers. Colorectal cancer mortality rates increased among men aged 45 to 54 years (AAPC, 1.3%; 95% CI, 0.5%-2.1%). Liver and intrahepatic bile duct cancer mortality increased for both men and women in all US census regions, uterine cancer mortality increased in all regions for women, and pancreatic cancer mortality increased in the Midwest for both men and women. Although these findings show an overall decrease in CSM among Asian American and Pacific Islander populations, specific cancer types exhibited increased mortality rates, with further disparities by sex and age. Targeted, culturally adapted clinical and public health interventions are needed to narrow disparities in cancer mortality.

Pesticides and prostate cancer incidence and mortality: An environment-wide association study.

Prostate cancer is the most common cancer among men in the United States, yet modifiable risk factors remain elusive. In this study, the authors investigated the potential role of agricultural pesticide exposure in prostate cancer incidence and mortality. For this environment-wide association study (EWAS), linear regression was used to analyze county-level associations between the annual use of 295 distinct pesticides (measured in kg per county) and prostate cancer incidence and mortality rates in the contiguous United States. Data were analyzed in two cohorts: 1997-2001 pesticide use with 2011-2015 outcomes (discovery) and 2002-2006 use with 2016-2020 outcomes (replication). The reported effect sizes highlight how a 1-standard-deviation increase in log-transformed pesticide use (kg per county) corresponds to changes in incidence. Analyses were adjusted for county-level demographics, agricultural data, and multiple testing. Twenty-two pesticides showed consistent, direct associations with prostate cancer incidence across both cohorts. Of these, four pesticides were also associated with prostate cancer mortality. In the replication cohort, each 1-standard-deviation increase in log-transformed pesticide use corresponded to incidence increases per 100,000 individuals (trifluralin, 6.56 [95% confidence interval (CI), 5.04-8.07]; cloransulam-methyl, 6.18 [95% CI, 4.06-8.31]; diflufenzopyr, 3.20 [95% CI, 1.09-5.31]; and thiamethoxam, 2.82 [95% CI, 1.14-4.50]). Limitations included ecological study design, potential unmeasured confounding, and lack of individual-level exposure data. The results of this study suggest a potential link between certain pesticides and increased prostate cancer incidence and mortality. These findings warrant further investigation of these specific pesticides to confirm their role in prostate cancer risk and to develop potential public health interventions.

Menopausal hormone therapy and incidence, mortality, and survival of breast cancer subtypes: a prospective cohort study

BackgroundMenopausal hormone therapy (MHT) is associated with an increased risk of postmenopausal breast cancer, predominantly the luminal A-like subtype. The impact of MHT on deaths from breast cancer subtypes is less understood. This study aimed to explore associations between MHT use and the incidence, mortality, and survival of intrinsic-like breast cancer subtypes.MethodsData from 160,881 participants with self-reported MHT use from the prospective Norwegian Women and Cancer Study were analyzed. Among them, 7,844 incident breast cancer cases, and 721 breast cancer-specific deaths occurred. Cox proportional hazard regression was performed to calculate hazard ratios (HRs) with 95% confidence intervals (CIs) for the association between MHT use and the incidence, mortality, and survival of breast cancer subtypes.ResultsMHT use was associated with increased risk of overall, luminal A-like, and luminal B-like breast cancer, with respective HRs of 1.44 (95% CI 1.36–1.52), 1.41 (95% CI 1.31–1.52), and 1.23 (95% CI 1.09–1.40) among current estrogen-progestin therapy (EPT) users compared with never users. The risk increased by 4%, 4%, and 2% per year of EPT use for overall, luminal A-like, and luminal B-like breast cancers, respectively. MHT use was also associated with increased risk of overall and luminal A-like breast cancer mortality, with HRs 1.61% (95% CI 1.36–1.91) and 2.15% (95% CI 1.51–3.05) increased risk among current EPT users compared with non-users. Among patients with breast cancer, pre-diagnostic MHT use was not associated with worse survival from overall breast cancer but was inversely associated with survival from triple-negative breast cancer (TNBC; HR death 0.41; 95% CI 0.24–0.73 among current users). Results varied significantly according to tumor subtype (pheterogeneity = 0.02).ConclusionsOur study suggests that MHT use increases the risk of incident and fatal overall and luminal A-like, and incident luminal B-like breast cancer but does not decrease overall survival among patients with breast cancer. Further research is needed to elucidate the mechanisms underlying MHT use and breast cancer lethality, and to explore whether MHT use among patients with TNBC is indeed free from harm.

Hypoxia induced cellular and exosomal RPPH1 promotes breast cancer angiogenesis and metastasis through stabilizing the IGF2BP2/FGFR2 axis.

Metastasis is the major cause of breast cancer mortality, with angiogenesis and tumor-released exosomes playing key roles. However, the communication between breast cancer cells and endothelial cells and its role in tumor metastasis remains unclear. Here, we characterize a long noncoding RNA, RPPH1, which is upregulated in breast cancer tissues and positively associated with poor prognosis. Hypoxia microenvironment upregulates the expression of RPPH1 in breast cancer cells, and promotes its packaging into exosomes through hnRNPA1, leading to the maintenance of stemness and aggressive traits in cancer cells and angiogenesis in endothelial cells. The function of cellular and exosomal RPPH1 was confirmed in the MMTV-PyMT mouse model, in which ASO-RPPH1 therapy effectively inhibited tumor progression and metastasis. Mechanistically, RPPH1 protects IGF2BP2 from ubiquitination-induced degradation, stabilizes N6-methyladenosine (m6A)-modified FGFR2 mRNA, and activates the PI3K/AKT pathway. Our research unveils the role of RPPH1 in breast cancer metastasis and highlights its potential as a therapeutic target.

Cirurgia citorredutora no câncer de ovário: uma revisão integrativa

Ovarian cancer ranks fifth on the list of causes of cancer mortality in women. The most used therapeutic approach for this condition is cytoreductive surgery combined with chemotherapy. This review aims to analyze survival related to cytoreductive surgery in cases of ovarian cancer. This occurred through an integrative review of articles from 2018 to 2022, following the PRISMA criteria, in the PubMed database. In total, 32 articles were found and of these, 18 entered this review. Therefore, cytoreduction followed by platinum/taxane-based chemotherapy is the current standard treatment for ovarian cancer. Survival outcomes are inversely related to initial and residual tumor burden after surgery. It appears that cytoreductive surgery is a viable technique that has been associated with good patient outcomes, including a median survival rate of 53 months.

The Frequency of Meal-Replacement Products Drinking and All-Cause, CVD, and Cancer Mortality.

Our study aimed to assess the associations between meal-replacement (MR) drinking and risks of all-cause, cardiovascular and cerebrovascular disease (CVD), and cancer mortality. The study was based on 6770 adults aged 20 years or older from the National Health and Nutrition Examination (NHANES) 2003-2006 with linked mortality data from the National Death Index for linked mortality records (until 31 December 2019). Respondents were categorized into four groups according to the frequency of MR drinking: ≤1 time per month (seldom), 2-3 times per month (monthly), 1-6 times per week (weekly), and ≥1 time per day (daily). The adjusted hazard ratios (aHRs) of MR drinking with all-cause, CVD, and cancer mortality were estimated by Cox proportional hazards regression models. Likelihood ratio tests were used to find potential interactions of MR drinking with age, sex, and BMI. During a median follow-up of 14.4 years, a total of 1668 death events were recorded among the study population. Compared to respondents who seldom drank MR, daily and weekly drinkers had greater risks of all-cause mortality (aHRs and 95% confidence intervals [CI]: 1.52 [1.17-1.97] for daily; 1.54 [1.24-1.91] for weekly). Stratified analyses indicated that the effects of MR on all-cause mortality were different between females and males and were more substantial among females (P for interaction: 0.003; daily female drinkers vs. daily male drinkers: 2.01 [1.40-2.90] vs. 1.24 [0.85-1.81]; weekly female drinkers vs. weekly male drinkers: 1.68 [1.26-2.24] vs. 1.36 [0.97-1.91]). Daily and weekly MR drinking might increase the risk of all-cause mortality.

Breast cancer incidence and mortality, by age, stage and molecular subtypes, by race/ethnicity in Canada.

Breast cancer (BC) characteristics and outcomes in Canada related to race/ethnicity are not currently documented. Age-specific and age-standardized BC incidence and mortality rates, age distribution of cases, proportions of stage, and molecular subtypes were calculated for women aged 20+, by race/ethnicity, using 2006 and 2011 Canadian Census Health and Environment Cohort databases of linked census, cancer, and death data. In 47105 BC cases, age-specific incidence rates were higher in Filipina (rate ratio (RR) = 1.27, 95%CI, 1.11-1.46) and multiethnicity (RR = 1.57, 95% CI, 1.18-2.08) compared to White women aged 40-49; and Filipina (RR = 1.16, 95% CI, 1.02-1.31) and Arab (RR = 1.3, 95% CI, 1.02-1.65) women aged 50-59. Median age at diagnosis was 63 among White women and 52-60 among other race/ethnicity groups, with 22.4%-41.1% of cases (P < .001) diagnosed before age 50 compared to 16.6% among White women. BC was diagnosed at stage I less frequently among Filipina (38.6%), Black (39.2%), South Asian (40.6%), and First Nations (40.7%) compared to White (46.5%) and Chinese (49.6%) (P < .05) women. Black women had higher proportions of BC diagnoses at stages III and IV combined (26.3%) than White women (17.0%, P = .001). The proportion of triple-negative BC among Black women (20.5%) was higher than among White (9.5%, P < .001). Compared to White, age-specific BC mortality rates were higher among Black women aged 40-49 (RR = 1.4, 1.06-1.85) as well as First Nations (RR = 1.21, 1.01-1.45) and Métis (RR = 1.48, 1.15-1.91) women aged 60-69. Compared to White women, other Canadian women had an earlier peak age of BC diagnosis and higher proportions of cases diagnosed under age 50. Although many race/ethnicity groups had lower BC incidence and mortality than White, the higher age-specific BC mortality among Black 40-49 and First Nations and Métis women 60-69 merits further investigation.

Breast cancer and its determinants in Ethiopia: a systematic review and meta-analysis.

Breast cancer is the leading cause of cancer morbidity and mortality among women. Still, there is a paucity of studies to know the magnitude of the problem in Ethiopia. Hence, this review was intended to pool the prevalence and identify the determinants of breast cancer in Ethiopia. A systematic review and meta-analysis was conducted. Databases like PubMed/MEDLINE, HINARI, Science Direct, and Google Scholar, as well as websites of organisationsI organizations,rewere searched between 25 February and 6 March 2023. All observational studies in Ethiopia that reported either the magnitude and/or determinants of breast cancer regardless of publication status were included. Two authors independently assessed and extracted the data. The Joanna Briggs Institute meta-analysis of statistics assessment and review instrument quality appraisal tool was used to assess the quality of the articles. Effect estimates were done by using the random-effects model. The meta-analysis results were displayed by using forest plots. Seventeen articles were reviewed with 24 435 total participants. The pooled proportion of breast cancer morbidity among patients with cancer was 20. 58% (95% CI 17.25%, 23.90%) in Ethiopia. Consuming packed foods (POR=2.12, 95% CI 1.41, 3.17), presence of high cholesterol (POR=4.08; 95% CI 2.75, 6.07), physical inactivity (POR=3.27; 95% CI 1.80, 5.94), high body mass index (BMI) (POR=2.27; 95% CI 0.85, 6.03), postmenopause (POR=2.25; 95% CI 1.63, 3.10), family history of cancer (POR=3.65; 95% CI 0.85, 15.71) and lack of breastfeeding (POR=2.76; 95% CI 0.90, 7.92) were the determinants of breast cancer. One of five patients with cancer is diagnosed with breast cancer in Ethiopia. Furthermore, more than a quarter of women with cancer suffer from breast cancer. Processed food consumption, high cholesterol in the body, lack of physical activity, high BMI, postmenopause, family history of cancer and lack of breastfeeding were the risk factors for breast cancer. The use of healthy food sources such as fruits and vegetables, and homegrown varieties of crops rather than seeking processed foods would help. CRD42023417733.

Transition towards cancer mortality predominance over cardiovascular disease mortality in Brazil, 2000–2019: a population-based study

Cardiovascular disease (CVD) and cancer are the first and second leading causes of death in Brazil and worldwide. However, an ongoing epidemiological transition in which cancer surpasses CVD has been observed in many high and middle-income countries. In this study, we provided a nationwide analysis of the transition towards cancer mortality predominance over CVD mortality in Brazil. We leveraged data from 5570 municipalities using the Mortality Information System and classified the causes of death using ICD-10 codes. Age-standardized CVD and cancer mortality rates were calculated annually between 2000 and 2019. Mortality rate ratios (MRRs=CVD rates divided by cancer rates) described the predominance of cancer or CVD mortality across municipalities and states. Choropleth maps displayed state-specific MRRs and the transition in the predominant cause of death over time. From 2000 to 2019, CVD mortality rates declined in 25 out of 27 states, whereas cancer mortality increased in 15 states, indicating a shift towards cancer predominance. While in 2000 cancer mortality was lower than CVD in all states and only exceeded the latter in 7% of the municipalities, by 2019 the gap narrowed considerably, with 13% of municipalities displaying higher cancer mortality rates vs CVD mortality rates. Additionally, higher household income correlated with higher mortality from cancer vs CVD. An ongoing epidemiological transition in which cancer mortality surpasses CVD mortality is occurring in Brazil, particularly in municipalities with higher household incomes. Our findings may provide important information for policymakers and public health practitioners in Brazil. National Council for Scientific and Technological Development (CNPq).

Postprandial Plasma Glucose With a Fasting Time of 4-7.9h Is Positively Associated With Cancer Mortality in US Adults.

This study investigated the association of postprandial plasma glucose (PPG) with cancer mortality using a general cohort of US adults. This cohort study included 14,860 US adults who attended the third National Health and Nutrition Examination Survey from 1988 to 1994, with mortality being followed up until December 31, 2019. The explanatory variable was the level of plasma glucose, including PPG with a fasting time of 0-3.9h (PPG0-3.9h) and 4-7.9h (PPG4-7.9h), plasma glucose with a fasting time ≥8h (PGfasting), and plasma glucose at 2h after oral glucose tolerance test (PG2hOGTT). Plasma glucose-associated cancer mortality risk was assessed using Cox proportional hazard models. A 1-natural-log-unit increase in PPG4-7.9h was associated with a higher multivariate-adjusted risk for cancer mortality [hazard ratio (HR), 3.24; 95% confidence interval (CI), 1.50-7.00]. However, PPG0-3.9h, PGfasting, PG2hOGTT, haemoglobin A1c, and insulin were not significantly associated with cancer mortality. The positive association of PPG4-7.9h with cancer mortality remained in those without a prior diagnosis of cancer. High PPG4-7.9h is associated with a higher cancer mortality risk in US adults. Lowering PPG4-7.9h may reduce cancer mortality.

Blood microRNA testing in participants with suspicious low-dose CT findings: follow-up of the BioMILD lung cancer screening trial

The proper management of suspicious radiologic findings is crucial to optimize the effectiveness of low-dose computed tomography (LDCT) lung cancer screening trials. In the BioMILD study, we evaluated the utility of combining a plasma 24-microRNA signature classifier (MSC) and LDCT to define the individual risk and personalize screening strategies. Here we aim to assess the utility of repeated MSC testing during annual screening rounds in 1024 participants with suspicious LDCT findings. The primary outcome was two-year lung cancer incidence in relation to MSC test results, reported as relative risk (RR) with 95% confidence interval (CI). Lung cancer incidence and mortality were estimated using extended Cox models for time-dependent covariates, yielding the respective hazard ratios (HR). Clinicaltrials.gov ID: NCT02247453. With a median follow-up of 8.5 years, the full study set included 1403 indeterminate LDCT (CTind) and 584 positive LDCT (CT+) results. A lung cancer RR increase in MSC+compared to MSC- participants was observed in both the CTind (RR: 2.5; 95% CI: 1.4-4.32) and CT+ (RR: 2.6; 95% CI: 1.81-3.74) groups and was maintained when considering stage I or resectable tumors only. A 98% negative predictive value in CTind/MSC- and a 30% positive predictive value in CT+/MSC+ lesions were recorded. At seven years' follow-up, MSC+ participants had a cumulative HR of 4.4 (95% CI: 3.0-6.4) for lung cancer incidence and of 8.1 (95% CI: 2.7-24.5) for lung cancer mortality. Our study shows that MSC can be reliably performed during LDCT screening rounds to increase the accuracy of lung cancer risk and mortality prediction and supports its clinical utility in the management of LDCT findings of uncertain malignancy. Italian Association for Cancer Research; Italian Ministry of Health; Horizon2020; National Cancer Institute (NCI); Gensignia LifeScience.

Obesity Paradox and the Effect of NT-proBNP on All-Cause and Cause-Specific Mortality.

In heart failure patients, obesity is associated with better outcomes as compared to normal weight, a phenomenon called the obesity paradox. To examine if obesity modifies the relationship between NT-proBNP and all-cause and cause-specific mortality in adults without coronary artery disease or heart failure history. We used the National Health and Nutrition Examination Survey (NHANES) data from 1999 to 2004 and linked it with mortality through December 31, 2019. Participants > 18 years were categorized into normal weight (BMI ≤ 25 kg/m2), overweight (BMI > 25-29.9 kg/m2) and obese (BMI > 29.9 kg/m2). NT-proBNP levels were categorized as low (< 126 pg/mL) or high (≥ 126 pg/mL). Using Cox proportional hazard models, we examined effect modification by obesity using interaction, without and with adjusting for potential confounders. Of the 12 621 participants, 2794 (22%) died during 202 859 person-years follow-up. In adjusted models, normal-weight participants with high NT-proBNP had 2 times higher all-cause mortality risk than those with low NT-proBNP (HR = 2.05; 95%CI = 1.74, 2.41; p < 0.001); however, this mortality risk was 27% lower in obese participants (HR interaction = 0.73; 95%CI = 0.59, 0.92; p = 0.008). Similarly, in normal-weight participants, the difference in other-cause mortality risk between high and low NT-proBNP participants was significant in adjusted models (HR = 2.27; 95%CI = 1.81, 2.85; p < 0.001) and obese participants had 48% lower other-cause mortality risk between those with high and low NT-proBNP (interaction HR = 0.52; 95%CI = 0.36, 0.77; p = 0.001). Conversely, obesity did not modify the relationship between NT-proBNP and cardiovascular or cancer mortality. In patients free of heart failure or coronary artery disease, obesity may be protective against mortality associated with high NT-proBNP.

Yield and Effectiveness of Two-Sample Fecal Immunochemical Test-based Screening Program for Colorectal Cancer

Colorectal cancer (CRC) incidence and mortality of China account for nearly 30% of the global attributable fraction. We aimed to estimate the yield and effectiveness of two-sample fecal immunochemical test (FIT)-based screening program in China. Eligible individuals were invited for two-sample FIT between 2007 and 2021, with positive ones (cutoff: 40 μg/g before 2013, and 20 μg/g thereafter) referred for colonoscopy. Participation rates, detection rates, and positive predictive values (PPVs) were calculated. Participants were classified into: FIT+ / colonoscopy compliers, FIT+ / colonoscopy non-compliers, and FIT- as controls. We compared CRC incidence and mortality, and calculated the age reaching comparable risk. Among 246,349 invitees, 150,524 (61.10%) participated in two-sample FIT, with 16,994 (11.29%) identified as FIT+; 12,816 (75.41%) underwent colonoscopy, yielding a detection rate and PPV of 0.57% and 6.70% for advanced neoplasia. Median follow-up was 10.58 years. Compared with FIT- participants, CRC incidence and mortality were relatively similar among FIT+ / colonoscopy compliers with hazard ratio (HR) and 95% confidence interval (CI) of 0.94 (0.75-1.19) and 1.62 (1.09-2.41), but higher among non-compliers with HR and 95% CI of 3.52 (2.85-4.34) and 4.41 (2.96-6.55). Taking CRC incidence and mortality risk of FIT- participants at age 50.0 as the benchmark, FIT+ / colonoscopy compliers reached same risk at 50.6 and 46.1 years, while non-compliers at age 38.0 and 37.9 years, respectively. Two-sample FIT could effectively identify high-risk populations, and colonoscopy compliance is associated with a lower risk of CRC incidence and mortality. This strategy might facilitate CRC screening practice in countries with large populations.

Investigating the Relationship Between β-Carotene Intake from Diet and Supplements, Smoking, and Lung Cancer Risk

β-carotene is a naturally occurring and safe dietary source of vitamin A that is associated with cancer risk reductions when consumed in typical dietary amounts. However, two clinical trials reported increased incidence of lung cancer and total mortality among heavy smokers taking β-carotene supplements (20 or 30 mg/day). Based on these findings, the Joint FAO/WHO Expert Committee on Food Additives withdrew Acceptable Daily Intake values for β-carotene (0-5 mg/kg bw). We evaluated relevant epidemiological and toxicological literature to assess the biological plausibility of this relationship and identified three mechanisms involving cellular proliferation signaling, a mode of action for cancer promotion. The overall weight of evidence consistently demonstrated typical dietary doses of β-carotene decreased cellular proliferation signaling via these mechanisms, even in the presence of smoke, while co-exposure to smoke and higher, supplemental doses increased cellular proliferation signaling through these same pathways. The production of excessive oxidative β-carotene metabolites via reactions with smoke constituents may be a key event underlying this relationship. Consistent with previous findings, our evaluation indicated consumption of up to 50 mg/day β-carotene does not present safety concerns for the non-smoking general population. Heavy smokers consuming less than 15 mg β-carotene/day are not expected to be at an increased risk of lung cancer.