Risk Of Cancer-related Mortality Research Articles

The impact of preoperative 5-alpha reductase inhibitors on functional outcomes and health-related quality of life following radical prostatectomy – A propensity score matched longitudinal study

ObjectivesWhile the impact of treatment with 5-alpha Reductase Inhibitors (5-ARI) on the risk of cancer-related mortality in men with prostate cancer (PC) has been extensively studied, little is known about the impact of preoperative 5-ARI use on patient-reported outcomes (PROs) following radical prostatectomy (RP).MethodsWithin our prospectively maintained institutional database of 5899 patients treated with RP for PC (2008– 2021), 99 patients with preoperative 5-ARI therapy were identified. A 1:4 propensity-score matched analysis of 442 men (n = 90 5-ARI, n = 352 no 5-ARI) was conducted. Primary endpoint was continence recovery using daily pad usage and ICIQ-SF. Health-related quality of life (HRQOL) was assessed using the validated EORTC QLQ-C30 and PR25 questionnaires. Multivariable Cox-regression-models tested the effect of preoperative 5-ARI treatment on continence-recovery (p < 0.05).ResultsPatients were followed up perioperatively, followed by annual assessments up to 60mo postoperatively. Preoperative mean ICIQ-SF score (2.2 vs. 0.9) was significantly higher in the 5-ARI cohort (p = 0.006). 24mo postoperatively, 68.6% (no 5-ARI) vs. 55.7% (5-ARI) had full continence recovery (p = 0.002). Multivariable Cox regression analysis, revealed preoperative 5-ARI treatment as an independent predictor for impaired continence recovery (HR 0.50, 95% CI 0.27–0.94, p = 0.03) In line, general HRQOL was significantly higher for patients without 5-ARI only up to 24mo postoperatively (70.6 vs. 61.2, p = 0.045). There was no significant impact of preoperative 5-ARI treatment on erectile function, biochemical recurrence-free survival and metastasis-free survival.ConclusionsPre-RP 5-ARI treatment was associated with impaired continence outcomes starting 24mo postoperatively, suggesting that preoperative 5-ARI treatment can impair the long-term urinary function recovery following RP.

Association between lipoprotein(a), fibrinogen and their combination with all-cause, cardiovascular disease and cancer-related mortality: findings from the NHANES

BackgroundThere is evidence indicating that both lipoprotein(a) [Lp(a)] and fibrinogen (FIB) are associated with mortality, However, the impact of their combination on mortality has not been determined. Thus, the aim of this study was to examine the association between the combination of Lp(a) and FIB with all-cause and cause-specific mortality.MethodsThis prospective cohort study enrolled 4,730 participants from the third National Health and Nutrition Examination Survey. The exposure variables included Lp(a), FIB and their combination, while the outcome variables consisted of all-cause, cardiovascular disease (CVD) and cancer-related mortality. Multivariate COX regression, subgroup analysis, sensitivity analysis and restricted cubic spline (RCS) were used to investigate the association between Lp(a), FIB and their combination with all-cause, CVD and cancer-related mortality.ResultsOver a median follow-up period of 235 months, 2,668 individuals died, including 1,051 deaths attributed to CVD and 549 deaths due to cancer. Multivariate Cox regression analyses revealed independent associations between both Lp(a) and FIB with all-cause, CVD, and cancer-related mortality. Compared to participants in the 1st to 50th percentiles of both Lp(a) and FIB, those in the 90th to 100th percentiles exhibited multivariable adjusted HRs of 1.813 (95% CI: 1.419–2.317, P < 0.001), 2.147 (95% CI: 1.483–3.109, P < 0.001) and 2.355 (95% CI: 1.396, 3.973, P = 0.001) for all-cause, CVD and cancer-related mortality, respectively. Subgroup and sensitivity analyses did not substantially attenuate the association between the combination of high Lp(a) and high FIB with the risk of all-cause and CVD-related mortality. Additionally, the RCS analysis showed that the relationship between Lp(a) and the risk of all-cause and cancer-related mortality, as well as the relationship between FIB and the risk of cancer-related mortality, were linear (P for nonlinearity > 0.05). Conversely, the relationship between Lp(a) and the risk of CVD-related mortality, as well as the relationship between FIB and the risk of all-cause and CVD-related mortality, were nonlinear (P for nonlinearity < 0.05).ConclusionsHigh levels of Lp(a) and FIB together conferred a greater risk of mortality from all-cause, CVD and cancer.

Frailty and all-cause and cancer-related mortality in cancer patients: A prospective cohort study

PurposeTo evaluate the associations between frailty and all-cause and cancer-related mortality. Additionally, the objective is to compare the magnitude of these associations between older adults and younger adults. MethodsWe gathered baseline data from NHANES (1999–2018) and developed a cumulative index consisting of 39 items to evaluate frailty. The National Death Index database was utilized to track the survival status of individuals. The Cox regression model was employed to estimate the associations between frailty status and all-cause and cancer-related mortality. ResultsUltimately, 3398 cancer patients were included in the analysis, comprising 910 younger adults and 2488 older adults. Compared to non-frail patients, the elevated all-cause and cancer-related mortality among pre-frail patients was not statistically significant (HRs = 1.312, 95%CI: 0.956–1.800, P = 0.092; HRs = 1.462, 0.811–2.635, P = 0.207). However, a significant elevation of both all-cause and cancer-related mortality risk was observed among frail patients (HRs = 2.213, 1.617–3.030, P < 0.001; HRs = 2.463, 95%CI = 1.370–4.429, P = 0.003). Frailty individuals demonstrated a more pronounced association with the prediction of all-cause mortality in younger (HRs = 2.230, 1.073–4.634, P = 0.032) than in older adults (HRs = 2.090, 1.475–2.960, P < 0.001). Sensitivity analysis consistently revealed robust results. RCS plots suggested a progressively escalating dose-response correlation between frailty and both all-cause and cancer-related mortality risk. ConclusionsPre-frailty did not result in an increase in mortality risks compared to non-frailty. However, frailty caused a higher all-cause and cancer-related mortality risk than non-frailty. Identifying those at risk and implementing targeted interventions may contribute to extending healthy life expectancy, regardless of age.

Folate Biomarkers, Folate Intake, and Risk of Death From All Causes, Cardiovascular Disease, and Cancer: A Systematic Review and Dose-Response Meta-Analysis of Prospective Cohort Studies.

Existing evidence on the relation between folate intake and biomarkers with mortality risk is controversial. Previous cohort studies were examined regarding folate intake and biomarkers in relation to risk of all-cause, cardiovascular disease- (CVD), and cancer-related mortality through a systematic review and meta-analysis. A systematic search was performed of the PubMed, Scopus, and ISI Web of Science databases up to July 2023. Prospective cohort studies examining the association of folate biomarkers (in serum, plasma, red blood cells) and intake with risk of all-cause, CVD-, and cancer-related mortality were considered. A random-effects model was applied to combine study-specific risk estimates. Dose-response relations were assessed by 1-stage weighted mixed-effects meta-analysis. A total of 25 cohorts with 423 304 participants, 36 558 all-cause, 12 662 CVD-, and 2426 cancer-related deaths were included. No significant association was observed between the highest levels of folate biomarkers and all-cause mortality risk (hazard ratio [HR], 0.91; 95% CI, 0.77-1.06; n = 17; I2 = 89.4%; P < .001), CVD-related mortality risk (HR, 0.97; 95% CI, 0.87-1.06; n = 11; I2 = 0.0%; P = .57), and cancer-related mortality risk (HR, 0.85; 95% CI, 0.69-1.05; n = 6; I2 = 57.8%; P = .04) compared with the lowest. Furthermore, each 10 nmol/L increase was marginally related to a 12% reduced all-cause mortality risk but not to CVD- and cancer-related mortality risk. A significant inverse association was found between highest intake of dietary folate and the lowest, and risk of all-cause (HR, 0.87; 95% CI, 0.78-0.96; n = 3; I2 = 63.6%; P = .06) and CVD (HR, 0.77; 95% CI, 0.57-0.93; n = 4; I2 = 80.2%; P = .002) mortality. This meta-analysis revealed a significant inverse relation between dietary folate intake and risk of all-cause and CVD mortality. Such an association was not found in the case of folate biomarkers. Further prospective studies are warranted to confirm these findings. PROSPERO registration no. CRD42023401700.

Disparities in breast cancer prevention initiatives at a comprehensive cancer center: Who are we serving?

1615 Background: Despite advances in personalized breast cancer risk assessment and screening, populations at highest risk for cancer-related mortality are often excluded. At the IU Simon Comprehensive Cancer Center, a high-risk screening program (HRSP) identifies and serves women at increased risk of breast cancer. Risk assessment using Tyrer Cuzick v.8 and Gail models is performed in mammography; women at increased risk are navigated to a clinic appointment to discuss individualized screening and prevention services including MRI, chemoprevention, and/or genetic testing. We hypothesize gaps in the demographic and socioeconomic (SES) characteristics of women seen for a HRSP appointment, compared to women receiving a cancer diagnosis at the same mammography sites. Methods: Retrospective review was performed of women who met criteria for the HRSP (age ≤65 and Gail 5 yr risk ≥3% or TC v.8 10-yr risk ≥8%, or recommended by the radiologist) and subsequently accepted, scheduled, and attended an appointment from 6/2020 to 6/2022 (n=233). This population was compared to women who were diagnosed with breast cancer at the same clinical sites over the same dates, without history of being evaluated in the HRSP. Age was restricted to ≤65 to match the HRSP population (n=685). Zip codes were used to calculate area-based SES by median household income and percent poverty. CDC social vulnerability index (SVI) was evaluated using the U.S. Census Bureau and American Community Survey (0=least vulnerable, 1=most vulnerable). Comparisons across groups by age, race, insurance status, area SES and SVI were made using the Wilcoxon or Chi-square test. Results: Cancer cases were significantly older than those attending the HRSP (median age 54 vs 49 p &lt; 0.001). Black patients represented 19.4% of participants diagnosed with cancer, versus 10.8% of participants attending the HRSP (p=0.0032). There was also a disparity in insurance coverage, with 83.8% of women seen in the HRSP being privately insured, versus 75.6% of women diagnosed with cancer (p=0.011). There was no statistical difference in SVI (0.64 vs 0.66 p=0.11) or area poverty rate (11.2 vs 12.0 p=0.26) between the groups; cancer cases came from areas with lower household income (69,611 vs 73,165 p=0.04). Conclusions: Women seen in the HRSP were more likely to be younger, White, privately insured, and from an area with higher household income, compared to women diagnosed with cancer in the same health system at the same mammography sites. This highlights disparities in access to individualized breast cancer interception such as chemoprevention, high-risk screening, and genetic testing, which may further existing disparities in breast cancer-related mortality based on race and SES. Further studies will investigate barriers and motivators to personalized breast cancer prevention in high-risk groups, and utilize community partnerships to develop equitable interventions.

Chronic intermittent hypoxia alters CD8+ expression in the bone marrow of C57BL/6 mice

Cytotoxic CD8+ cells are critical in anticancer immune response and have become prevalent in immunotherapies over the past decade. Anti-LAG3/anti-PD1 combined immunotherapies increase the number of CD8+ cells. Moderate to severe sleep apnea increases the risk of cancer-related mortality. Chronic intermittent hypoxia, a feature of sleep apnea, decreases the percentage of perforin-expressing CD8+ cells, impairing cytotoxicity. Our objective is to determine the distribution of Prf1(perforin), LAG3(lymphocyte-activation gene 3), and PDCD1(programmed cell death 1) in C57BL/6 mice exposed to chronic intermittent hypoxia (CIH). We hypothesize that Prf1, PDCD1, and LAG3 will be expressed on three discrete clusters with a higher expression of LAG3 and PDCD1 and lower expression of Prf1 between C57BL/6 mice exposed to chronic intermittent hypoxia and normoxia. Bone marrow from the femur of C57BL/6 mice exposed to chronic intermittent hypoxia or normoxia was harvested. Bone marrow mononuclear cells were isolated, RNA was extracted, and single-cell RNA sequencing was performed. Loupe browser was used to re-cluster and quantify expression for genes of interest. Prf1 and PDCD1 are expressed in CD3+CD8−CD4− cluster and LAG3 is expressed in CD3−CD8+CD4+ cluster. LAG3 and Prf1 are present among the top ten genes, while PDCD1 is not in those clusters. Further analysis of the top ten genes of CD3+CD8−CD4− has demonstrated they are a group of natural killer cells. Contradictory to our expectation, Prf1 and PDCD1 are present in CD3+CD8−CD4− cluster while LAG3 is present in CD3−CD8+CD4+ cluster. Further analysis is necessary to determine the underlying mechanisms causing these changes. 5R01CA244271-02. This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

Abstract 6083: Inter-observer agreement in ultrasound-detected steatotic liver in the Chile Biliary Longitudinal Study (BiLS)

Abstract Background: Metabolic-associated steatotic liver disease (MASLD) is a prevalent chronic liver condition with an increased risk of cancer-related mortality. In Latin America, MASLD prevalence is estimated at 40%, with Chile reporting rates of 47.5% in 2019. Early detection is crucial for MASLD control and management. Liver biopsy, the gold standard for diagnosis, is invasive and costly. Ultrasound (US) is a preferred alternative, yet its precision varies depending on the observer interpretation. Methods: We conducted a cross-sectional analysis of a subset of baseline US images from the Chile Biliary Longitudinal Study (Chile BiLS), a cohort of women aged 50-74 with gallstones in Chile. Of the 4,032 participants recruited from Cautín Province in the Araucanía region, a random sample of 10% of the images were selected for review by a radiologist from Baylor College of Medicine (Observer 1) and compared to the original readings generated at the baseline exam by a team of Chile BiLS ultrasound technicians. To assess reproducibility, 33 blinded duplicate images from the 10% sample were reanalyzed by Observer 1 and an additional Chile BiLS technician who was not part of the original baseline team (Observer 2). Inter- and intra-observer agreement was assessed using weighted kappa values. Images were categorized as none, mild, moderate/severe. Results: Of the 409 images reviewed, agreement between Observer 1 and original readings across all categories of steatosis was poor (kappa: 0.09; CI 95% 0.06;0.11, p &amp;lt;0.001). The 33 duplicates compared to the original readings showed slight agreement for Observer 1 (kappa: 0.11 CI 95% 0.02;0.20, p &amp;lt;0.05) and fair for Observer 2 (kappa: 0.28 (CI 95% 0.07 - 0.49, p &amp;lt;0.001). The intra-observer agreement for Observer 1 was moderate, with a kappa of 0.41 (CI 95% 0.09 - 0.74, p &amp;lt;0.05), and for Observer 2, it was substantial with a weighted kappa of 0.69 (CI 95% 0.5 - 0.9, p &amp;lt;0.001). Conclusion: The study highlights the variability in US interpretation of hepatic steatosis, emphasizing the importance of standardized training and methodology. US's sensitivity and specificity is operator dependence, which impacts the diagnostic interpretation. Our findings underscore the significance of inter and intra-observer comparisons for optimal diagnosis, especially when US is the primary diagnostic tool in MASLD assessment. Finally, our results emphasize the importance of group training. Observer 2, who underwent the same training as the original Chile BiLS ultrasound technicians and was consistently exposed to this technique as a diagnostic method, exhibited more consistent results. This reinforces the importance of collective training initiatives to enhance the reliability and accuracy of US in MASLD diagnosis. Citation Format: Maria Spencer Sandino, Vanessa Van De Wyngard, David Wynne, Maya Balakrishnan, Noldy Mardones, Ruth Pfeiffer, Allan Hildesheim, Catterina Ferreccio, Jill Koshiol. Inter-observer agreement in ultrasound-detected steatotic liver in the Chile Biliary Longitudinal Study (BiLS) [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 6083.

Neck management in metastatic cutaneous squamous cell carcinoma of the head and neck.

Optimal neck management remains unclear in head and neck cutaneous squamous cell carcinoma (HNcSCC) with parotid metastasis. Our goal was to compare the impact of different cervical treatments on HNcSCC with parotid metastasis. Patients were retrospectively included. The primary outcome variables were regional control (RC) and disease-specific survival (DSS). The impacts of observation, elective neck irradiation (ENI), and elective neck dissection (END) were analyzed using the Cox model and presented as hazard ratios (HRs) and 95% confidence intervals (CIs). In total, 268 patients were enrolled. In the Cox model for RC, compared with ENI, observation was associated with a significantly higher risk of regional recurrence (p = 0.001, HR = 2.50, 95%CI = 1.45-4.30). However, END showed a comparable influence on regional recurrence (p = 0.246, HR = 0.70, 95%CI = 0.38-1.28). In the Cox model for DSS, END demonstrated a similar HR of 0.62 (95%CI = 0.30-1.26) compared to ENI (p = 0.184). However, patients who underwent observation were associated with an additional nearly twofold risk of cancer-related mortality (HR = 2.85, 95%CI = 1.55-5.23). Subgroup analysis showed that ENI predicted comparable RC (p = 0.389) and DSS (p = 0.346) in patients with one or two metastatic parotid lymph nodes, but worse RC (p = 0.007) and DSS (p = 0.024) in patients with more than three positive lymph nodes. In HNcSCC with parotid metastasis, elective treatment of neck lymph nodes with END or ENI should always be performed.

Insomnia disorder and cancer mortality in South Korea: a secondary analysis of musculoskeletal disease cohort.

The association between insomnia disorder and cancer-related mortality risk remains controversial. Therefore, this study aimed to investigate the correlation between insomnia disorder and cancer-related mortality. Patients who were diagnosed with musculoskeletal disease (MSD) between 2010 and 2015 were included in this study as a secondary analysis of a patient cohort with MSD in South Korea. Cancer mortality was evaluated between January 1, 2016, and December 31, 2020, using multivariable Cox regression modeling. Patients with and without insomnia disorder constituted the ID and non-ID groups, respectively. The final analysis incorporated a total of 1,298,314 patients diagnosed with MSDs, of whom 11,714 (0.9%) died due to cancer. In the multivariable Cox regression model, the risk of total cancer-related mortality was 14% (hazard ratio [HR], 1.14; 95% confidence interval [CI], 1.10-1.19; P < 0.001) higher in the ID group than in the non-ID group. Moreover, the ID group had a higher risk of mortality due to esophageal (HR, 1.46; 95% CI, 1.08-1.96; P = 0.015), colorectal (HR, 1.20; 95% CI, 1.05-1.36; P = 0.007), head and neck (HR, 1.39; 95% CI, 1.01-1.94; P = 0.049), lung (HR, 1.17; 95% CI, 1.08-1.27; P < 0.001), and female genital organ (HR: 1.39, 95% CI: 1.09, 1.77; P = 0.008) cancers; leukemia; and lymphoma (HR, 1.30; 95% CI, 1.12-1.49; P < 0.001). Insomnia disorder was associated with elevated overall cancer mortality in patients with MSDs, which was more evident for cancer mortality due to esophageal, colorectal, head and neck, lung, and female genital organ cancers; leukemia; and lymphoma.

Impact of oseltamivir on the risk of cancer.

Mounting evidence has revealed the anti-cancer activity of various anti-viral drugs. Oseltamivir phosphate (OP), namely Tamiflu®, is routinely used to combat influenza infections. Although evidence has indicated the anti-cancer effects of OP in vitro and in vivo, little information is known about the effect of OP use on cancers in humans. A nationwide population-based cohort study involving 13,977,101 cases with 284,733 receiving OP was performed to examine the association between OP use and cancers using the National Health Insurance Research Database in Taiwan between 2009 and 2018. The cohort study found that OP users showed a significantly lower incidence of lung cancer, colon cancer, liver, and intrahepatic bile duct cancer, oral cancer, pancreas cancer, esophagus cancer, stomach cancer, and prostate cancer. Additionally, OP users exhibited a lower risk of cancer-related mortality (adjusted HR=0.779; 95% confidence interval [CI] 0.743-0.817; p<0.001) and a reduced risk of developing liver cancer (adjusted HR=0.895; 95% CI 0.824-0.972; p=0.008), esophagus cancer (adjusted HR=0.646; 95% CI 0.522-0.799; p<0.001) and oral cancer (adjusted HR=0.587; 95% CI 0.346-0.995; p=0.048). Notably, OP users had a significant reduction in liver cancer occurrence over a 10-year period follow-up and a lower cancer stage at liver cancer diagnosis. These findings first suggest the beneficial effects and therapeutic potential of OP use for certain cancers, especially liver cancer.

Metformin may improve the outcome of patients with colorectal cancer and type 2 diabetes mellitus partly through effects on neutrophil extracellular traps

BackgroundAlthough metformin reduces the risk of cancer-related mortality in patents with type 2 diabetes, the mechanism of its anti-cancer effects has not been fully understood.MethodImpact of metformin on survival was examined in patients who underwent curative colectomy for colorectal cancer (CRC). The effects of metformin in neutrophil extracellular traps (NETs) were examined with in-vitro experiments and multiplex immunohistochemistry of surgically resected CRC specimens.ResultsPrior intake of metformin prolonged relapse-free (P = 0.036) and overall survival (P = 0.041) in 289 patients with T2DM to the comparable levels to those of 1576 non-diabetic patients. Metformin reduced the production of NETs stimulated with lipopolysaccharide or HT-29 colon cancer cells to 60% of control. Neutrophils markedly suppressed the chemotactic migration of activated T cells in an NET-dependent manner, which was reversed by metformin treatment up to approximately half of the migration without neutrophils. Immunohistochemical analysis revealed a significant association between metformin intake and a reduction in the numbers of tumor-associated neutrophils (TANs) and NETs. Simultaneously, metformin intake was found to increase the presence of CD3(+) and CD8(+) tumor-infiltrating T cells (TILs), particularly at the tumor-invasion front, especially in areas with fewer TANs and NETs.ConclusionMetformin suppresses the diabetes-associated enhancement of NET formation, which can augment the infiltration of TILs in CRC tissues. The anti-tumor effect of metformin in patients with T2DM may be, at least partly, attributable to the inhibition of NETs.

Effect of examining lymph nodes count on mortality risk in resected T1 non-small-cell lung cancer.

This study aims to estimate the effect of the examined lymph node count (ELNC) on the cancer-related mortality risk and non-cancer-related mortality risk in patients with resected T1 non-small-cell lung cancer (NSCLC). Patients diagnosed as primary T1 NSCLC between 2000 and 2017 were extracted from the Surveillance, Epidemiology and End Results database. Patients were divided into 2 groups according to the ELNC cutoff value, which was calculated based on overall survival outcomes. Propensity score matching was used to equalize the differences in baseline characteristics between groups. A total of 38242 resected T1 NSCLC patients were extracted from the database with the ELNC cutoff value of 8. After propensity score matching, 27676 patients were included in this study. Examining ≥8 ELNC was associated with a more accurate assessment of lymph node (LN) metastasis and significantly improving the prognosis. These trends remained consistent in subgroup analysis by histology type. In competing risk mode, examining ≥8 LNs could significantly reduce the risk of death from lung cancer, risk of death from chronic obstructive pulmonary disease, and risk of death from cardiac diseases. In the subgroup analysis, these trends were consistent. Given the mortality risk associated with lung cancer, chronic obstructive pulmonary disease, and cardiac diseases, at least 8 LNs should be examined in surgery for T1 NSCLC.

Association between cytomegalovirus infection and cancer‑related mortality in the US adults

PurposeIn a nationwide cohort of US adults, an exploration of the association between cytomegalovirus (CMV) infection and cancer‑related mortality was conducted. Materials and methodsWe acquired data from the National Health and Nutrition Examination Survey III (1988–1994), including 11,138 individuals who were aged 18–90 years at enrollment and underwent CMV serology assessments. CMV infection was determined by CMV antibody testing. Cancer‑related mortality status was ascertained until December 2019 utilizing the National Death Index linkage data and determined by neoplasms. The Cox proportional hazard model was applied to estimate the potential association between CMV infection and the risk of cancer-related mortality. ResultsDuring a median follow-up of 26.1 years, 1514 cancer‑related deaths were identified in the study cohort. After adjusting for age, sex, and ethnicity, CMV infection was associated with a higher hazard of cancer‑related mortality (hazard ratio [HR]: 1.39, 95 % CI: 1.13, 1.70). Further adjustments for body mass index, family income, and smoking status slightly attenuated the magnitude of the association (HR: 1.24, 95 % CI: 1.00, 1.53). However, no significant interaction was observed among gender by subgroup analysis. ConclusionsCMV infection might be an independent risk factor for cancer‑related mortality among US adults. Future studies could focus on the mechanisms through which CMV infection influences mortality induced by neoplasms and develop targeted interventions to reduce the risk.

Potential Determinants of Thyroid Peroxidase Antibodies and Mortality Risk: Results From the ELSA-Brasil Study.

The presence of thyroid peroxidase antibodies (TPOAbs) may be considered as an indicator of adverse health outcomes. We aimed to investigate the potential determinants of TPOAb levels and to analyze the association between TPOAb titers and the risk of all- and specific-cause mortality. Baseline and longitudinal data of 13 187 participants from the ELSA-Brasil Study were analyzed. We investigated the association of TPOAb, detectability, positivity, and persistent positivity with sociodemographic and lifestyle factors using logistic regressions. Cox proportional hazards and Fine-Gray subdistribution hazard regression analyses were used to verify the association of TPOAbs with mortality. The determinants of TPOAb detectability and positivity were younger age, higher body mass index, female sex, and former and current smoking status. Black, mixed, and other self-reported races, intermediate and higher education, and heavy drinking were determinants of detectable and positive TPOAb levels. Female sex, White race, and former smoking were determinants of persistent TPOAb positivity at 2 visits, although only the female sex maintained its association at 3 visits. Moreover, after multivariate adjustment, there were associations between higher levels of TPOAbs and higher risk of cancer-related mortality among men, and TPOAb detectability and mortality by other causes among women. Sociodemographic and lifestyle-related factors were determinants of multiple TPOAb categories. TPOAb levels were associated with mortality risk; however, the low mortality rate in this sample might have compromised this finding. We suggest further studies to explore the clinical importance of detectable TPOAb levels, not only its positivity, as a potential marker of inflammation.

Early life PM2.5 exposure, childhood cognitive ability and mortality between age 11 and 86: A record-linkage life-course study from Scotland

BackgroundLiving in areas with high air pollution concentrations is associated with all-cause and cause-specific mortality. Exposure in sensitive developmental periods might be long-lasting but studies with very long follow-up are rare, and mediating pathways between early life exposure and life-course mortality are not fully understood. MethodsData were drawn from the Scottish Longitudinal Study Birth Cohort of 1936, a representative record-linkage study comprising 5% of the Scottish population born in 1936. Participants had valid age 11 cognitive ability test scores along with linked mortality data until age 86. Fine particle (PM2.5) concentrations estimated with the EMEP4UK atmospheric chemistry transport model were linked to participants’ residential address derived from the National Identity Register in 1939 (age 3). Confounder-adjusted Cox regression estimated associations between PM2.5 and mortality; regression-based causal mediation analysis explored mediation through childhood cognitive ability. ResultsThe final sample consisted of 2734 individuals with 1608 deaths registered during the 1,833,517 person-months at risk follow-up time. Higher early life PM2.5 exposure increased the risk of all-cause mortality (HR = 1.03, 95% CI: 1.01–1.04 per 10 μg m−3 increment), associations were stronger for mortality between age 65 and 86. PM2.5 increased the risk of cancer-related mortality (HR = 1.05, 95% CI: 1.02–1.08), especially for lung cancer among females (HR = 1.11, 95% CI: 1.02–1.21), but not for cardiovascular and respiratory diseases. Higher PM2.5 in early life (≥50 μg m−3) was associated with lower childhood cognitive ability, which, in turn, increased the risk of all-cause mortality and mediated 25% of the total associations. ConclusionsIn our life-course study with 75-year of continuous mortality records, we found that exposure to air pollution in early life was associated with higher mortality in late adulthood, and that childhood cognitive ability partly mediated this relationship. Findings suggest that past air pollution concentrations will likely impact health and longevity for decades to come.

Longitudinal Changes in Smoking Behaviors and Cancer-Related Mortality Risk in Middle-Aged Korean Women.

This study investigated association between smoking habit change and cancer-related mortality risk in Korean women. Study population were women aged ≥ 40 years who underwent two biennial cancer screenings during 2009-2012 and were followed up until 2020. Participants were grouped into sustained nonsmokers, sustained quitters, new quitters, relapsers/smoking initiators, and sustained smokers. Outcomes included all-cause and cancer-related deaths. Cox regression and competing risk analysis was used to assess association between smoking habit change and mortality risk. Of 2,892,590 women, 54,443 death cases were recorded (median follow-up of 9.0 years). Compared with sustained nonsmokers, mortality risk from all causes and cancer-related causes increased in all other smoking groups. Cancer-related risk increased 1.22-fold among sustained quitters (95% confidence interval [CI], 1.10 to 1.36), 1.56-fold (95% CI, 1.40 to 1.75) in new quitters, 1.40-fold (95% CI, 1.21 to 1.62) in relapsers/smoking initiators, and 1.61-fold (95% CI, 1.46 to 1.78) in sustained smokers compared with sustained nonsmokers. Women who were sustained smokers with higher smoking intensity had a higher mortality risk in terms of hazard ratios compared to nonsmokers (< 5 pack-years 2.12-fold, 5-10 pack-years 2.15-fold, and > 10 pack-years 2.27-fold). Quitting smoking earlier is critical for preventing death from all causes and cancer among female smokers.

Association Between Visceral Fat Area and Cancer Prognosis: A Population-Based Multicenter Prospective Study

BackgroundDiverse indicators have been used to represent adipose tissue, while the relationship between body adipose mass and the prognosis of patients with cancer remains controversial. ObjectiveThis study aimed to explore the indicators of optimal body composition that represent body fat mass to predict risk of cancer-related mortality. MethodsWe conducted a population-based multicenter prospective cohort study of patients with initial cancer between February 2012 and September 2020. Clinical information, body composition indicators, hematologic test results, and follow-up data were collected. Body composition indicators were analyzed using principal component analysis to select the most representative indicators, and the cutoff value was set according to the optimal stratification method. The hazard ratio (HR) for mortality was calculated using Cox proportional hazards regression models. ResultsAmong 14,018 patients with complete body composition data, visceral fat area (VFA) is a more optimal indicator for body fat content (principal component index: 0.961) than body mass index (principal component index: 0.850). The cutoff points for VFA in terms of time to mortality were 66 cm2 and 102 cm2 for gastric/esophageal cancer and other cancers, respectively. Among the 2788 patients treated systemically, multivariate analyses demonstrated that a lower VFA was associated with a higher risk of death in patients with cancer of diverse types (HR: 1.33; 95% CI: 1.08, 1.64; P = 0.007), especially gastric cancer (HR: 2.13; 95% CI: 1.3, 3.49; P = 0.003), colorectal cancer HR: 1.81; 95% CI: 1.06, 3.08; P = 0.030) and nonsmall-cell lung cancer (HR: 1.27; 95% CI: 1.01, 1.59; P = 0.040). ConclusionVFA is an independent prognostic indicator of muscle mass in patients with diverse types of cancer, particularly gastric, colorectal, and nonsmall-cell lung cancers. Trial registration numberChiCTR1800020329.

Association between Serum C-Reactive Protein Concentrations and Risk of Cancer-Related Mortality in Patients Undergoing Hemodialysis: 10-Year Outcomes of the Q-Cohort Study

Introduction: Cancer constitutes a major source of morbidity and mortality among people undergoing hemodialysis (HD). A systemic inflammatory response is associated with the incidence and prognosis of cancer in the general population. However, the effect of systemic inflammation on cancer-related mortality in patients undergoing HD remains unclear. Methods: We analyzed 3,139 patients registered in the Q-Cohort Study, which is a multicenter, observational cohort study of patients on hemodialysis in Japan. The primary outcome was cancer-related mortality during a 10-year follow-up. The covariate of interest was serum C-reactive protein (CRP) concentrations at baseline. The patients were divided into tertiles based on their serum CRP concentrations at baseline (tertile [T] 1: ≤0.07; T2: 0.08–0.24; and T3: ≥0.25). The association between serum CRP concentrations and cancer-related mortality was calculated using the Cox proportional hazards model and the Fine-Gray subdistribution hazards model with non-cancer-related death as a competing risk. Results: During the 10-year follow-up, 216 patients died of cancer. In the multivariable analysis, the risk of cancer-related mortality in the highest tertile (T3) of serum CRP concentrations was significantly higher than that in the lowest tertile (T1) (multivariable-adjusted hazard ratio [95% confidence interval]: 1.68 [1.15–2.44]). This association remained consistent in the competing risk model, in which the subdistribution hazard ratio was 1.47 and the 95% confidence interval was 1.00–2.14 for T3 compared with T1. Conclusion: Higher serum CRP concentrations are associated with an increased risk of cancer-related mortality in patients undergoing maintenance HD.

Dietary Carbohydrate and Fat Intakes and Risk of Mortality in the Japanese Population: the Japan Multi-Institutional Collaborative Cohort Study

BackgroundPrevious cohort studies have yielded contradictory findings regarding the associations of dietary carbohydrate and fat intakes with risks of mortality. ObjectivesWe examined long-term associations of carbohydrate and fat intakes with mortality. MethodsIn this cohort study, 34,893 men and 46,440 women aged 35–69 y (mean body mass index of 23.7 and 22.2 kg/m2, respectively) were followed up from the baseline survey (2004–2014) to the end of 2017 or 2018. Intakes of carbohydrate, fat, and total energy were estimated using a food frequency questionnaire. Hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated for all-cause and cause-specific mortality according to percentage of energy intakes of carbohydrate and fat. ResultsDuring a mean 8.9-y follow-up, we identified 2783 deaths (1838 men and 945 women). Compared with men who consumed 50% to <55% of energy from carbohydrate, those who consumed <40% carbohydrate energy experienced a significantly higher risk of all-cause mortality (the multivariable-adjusted HR: 1.59; 95% CI: 1.19–2.12; P-trend = 0.002). Among women with 5 y or longer of follow-up, women with high-carbohydrate intake recorded a higher risk of all-cause mortality; the multivariable-adjusted HR (95% CI) was 1.71 (0.93–3.13) for ≥65% of energy from carbohydrate compared with that for 50% to <55% (P-trend = 0.005). Men with high fat intake had a higher risk of cancer-related mortality; the multivariable-adjusted HR (95% CI) for ≥35% was 1.79 (1.11–2.90) compared with that for 20% to <25%. Fat intake was marginally inversely associated with risk of all-cause and cancer-related mortality in women (P-trend = 0.054 and 0.058, respectively). ConclusionsAn unfavorable association with mortality is observed for low-carbohydrate intake in men and for high-carbohydrate intake in women. High fat intake can be associated with a lower mortality risk in women among Japanese adults with a relatively high-carbohydrate intake.

Health disparities among patients with Ewing sarcoma in Florida.

e18549 Background: Ewing sarcoma (ES) is the second most common malignant bone tumor in children and young adults. Although usually localized, subclinical metastatic disease is often present. Treatment includes multi-agent chemotherapy with surgery or radiation for local control. Though overall survival (OS) has improved to 70% for localized disease, mortality from recurrent or metastatic disease remains high. Although, ES is most common among Non-Hispanic White adolescent males, prior population-based ES studies utilizing Surveillance, Epidemiology, and End Results (SEER) have shown increased mortality among White Hispanics, Blacks, and those of low socioeconomic status (SES). Florida is not part of SEER but is home to a unique population with high proportions of immigrants and Hispanics of distinct backgrounds including Cubans, Puerto Ricans, and South Americans that contrasts to the Mexican Hispanic majority in other US states. As there are no prior population-based studies examining ES in Florida, the role of racial/ethnic disparities on outcomes among this diverse patient population remains unknown. By utilizing the Florida Cancer Data System (FCDS) for ES patients, this study will assess overall racial/ethnic disparities, evaluate the impact of racial/ethnic disparities on OS, and compare ES incidence rates in Florida with national SEER-21 rates to assess risk. Methods: This retrospective secondary analysis examined all patients diagnosed with ES (2005-2018) in Florida (n = 411) and SEER-21 (n = 1,513). Age-adjusted incidence (AAI) with 95% confidence interval (95%CI) was analyzed for the entire group and OS was estimated using Kaplan-Meier survival analysis. Univariable and multivariable analyses using Cox regression models were performed for variables of interest—race/ethnicity, age, sex, year of diagnosis, site of disease, staging, SES, and insurance type. Adjusted hazard ratio (aHR) with 95%CI were calculated. Results: Per the FCDS, there was a higher incidence of ES in Hispanic males (AAI 2.6; 95%CI: 2.0-3.2 per 1,000,000; n = 84) as compared to the SEER (1.2; 1.1-1.4; n = 250). Among non-metastatic ES, Hispanics had an increased risk for cancer-related mortality compared to Non-Hispanic Whites (aHR 2.9; 95%CI: 1.46-5.74; p =0.002), after adjusting for all other variables. In the full model (all cases regardless of stage at diagnosis), older age and distant metastasis were statistically significant factors for poor OS while SES and insurance status were not. Conclusions: Hispanics in Florida are of interest for ES with a higher-than-expected incidence compared to the US and remarkably worse survival for non-metastatic disease compared to Non-Hispanic Whites. Further in-depth studies are needed to examine why this disparity exists, but it is potentially multifactorial. This is the first known study for ES health disparities in Florida and provides updated national data for comparison.