RESUMEN
Importance: Molecular subtypes of HPV-associated Head and Neck Squamous Cell Carcinoma (HNSCC), named IMU (immune strong) and KRT (highly keratinized), are well-recognized and have been shown to have distinct mechanisms of carcinogenesis, clinical outcomes, and potentially differing optimal treatment strategies. Currently, no standardized method exists to subtype a new HPV+ HNSCC tumor. Our paper introduces a machine learning-based classifier and webtool to reliably subtype HPV+ HNSCC tumors using the IMU/KRT paradigm and highlights the importance of subtype in HPV+ HNSCC. Objective: To develop a robust, accurate machine learning-based classification tool that standardizes the process of subtyping HPV+ HNSCC, and to investigate the clinical, demographic, and molecular features associated with subtype in a meta-analysis of four patient cohorts. Data Sources: We conducted RNA-seq on 67 HNSCC FFPE blocks from University of Michigan hospital. Combining this with three publicly available datasets, we utilized a total of 229 HPV+ HNSCC RNA-seq samples. All participants were HPV+ according to RNA expression. An ensemble machine learning approach with five algorithms and three different input training gene sets were developed, with final subtype determined by majority vote. Several additional steps were taken to ensure rigor and reproducibility throughout. Study Selection: The classifier was trained and tested using 84 subtype-labeled HPV+ RNA-seq samples from two cohorts: University of Michigan (UM; n=18) and TCGA-HNC (n=66). The classifier robustness was validated with two independent cohorts: 83 samples from the HPV Virome Consortium and 62 additional samples from UM. We revealed 24 of 39 tested clinicodemographic and molecular variables significantly associated with subtype. Results: The classifier achieved 100% accuracy in the test set. Validation on two additional cohorts demonstrated successful separation by known features of the subtypes. Investigating the relationship between subtype and 39 molecular and clinicodemographic variables revealed IMU is associated with epithelial-mesenchymal transition (p=2.25×10-4), various immune cell types, and lower radiation resistance (p=0.0050), while KRT is more highly keratinized (p=2.53×10-8), and more likely female than IMU (p=0.0082). Conclusions and Relevance: This study provides a reliable classifier for subtyping HPV+ HNSCC tumors as either IMU or KRT based on bulk RNA-seq data, and additionally, improves our understanding of the HPV+ HNSCC subtypes.
RESUMEN
Existing research, including work specific to COVID-19, suggests that endorsement by medical practitioners increases vaccine uptake. Yet, vaccine hesitancy persists despite health professionals continuing to widely endorse multiple vaccines to combat COVID-19 since late 2020. Could endorsement by other trusted leaders reduce vaccine hesitancy? Although some studies suggest that trust in religious leaders can influence individuals' health attitudes and behaviors, the evidence is mixed. Our study explores the potential added value of messaging by religious leaders across religious traditions - specifically, it asks whether their endorsement of the COVID-19 vaccine might increase vaccine uptake in an environment where health professionals are already endorsing vaccines. To investigate this question, we conducted an online survey experiment with 6,000 respondents across five countries with different dominant religions (Buddhism, Christianity, and Islam). Respondents were randomly assigned to either a control group that only included endorsement by medical practitioners or a treatment group that added either endorsement by religious leaders or, for comparative purposes, endorsement by political leaders. We found that endorsement by religious leaders reduced vaccine hesitancy only in one country. These findings corroborate existing research that medical practitioners are the best line of defense to combat vaccine hesitancy. They also suggest the limitations of endorsement by non-experts.
Asunto(s)
COVID-19 , Vacunas , Humanos , Vacunas contra la COVID-19 , Vacilación a la Vacunación , Agujas , Actitud Frente a la Salud , VacunaciónRESUMEN
BACKGROUND: Head and neck cancer (HNC) has low 5-year survival, and evidence-based recommendations for tertiary prevention are lacking. Aspirin improves outcomes for cancers at other sites, but its role in HNC tertiary prevention remains understudied. METHODS: HNC patients were recruited in the University of Michigan Head and Neck Cancer Specialized Program of Research Excellence (SPORE) from 2003 to 2014. Aspirin data were collected through medical record review; outcomes (overall mortality, HNC-specific mortality, and recurrence) were collected through medical record review, Social Security Death Index, or LexisNexis. Cox proportional hazards models were used to evaluate the associations between aspirin use at diagnosis (yes/no) and HNC outcomes. RESULTS: We observed no statistically significant associations between aspirin and cancer outcome in our HNC patient cohort (n = 1161) (HNC-specific mortality: HR = 0.91, 95% CI = 0.68-1.21; recurrence: HR = 0.94, 95% CI = 0.73-1.19). In analyses stratified by anatomic site, HPV status, and disease stage, we observed no association in any strata examined with the possible exception of a lower risk of recurrence in oropharynx patients (HR = 0.60, 95% CI 0.35-1.04). CONCLUSIONS: Our findings do not support a protective association between aspirin use and cancer-specific death or recurrence in HNC patients, with the possible exception of a lower risk of recurrence in oropharynx patients.
Asunto(s)
Aspirina , Neoplasias de Cabeza y Cuello , Humanos , Aspirina/uso terapéutico , Neoplasias de Cabeza y Cuello/tratamiento farmacológico , Modelos de Riesgos ProporcionalesRESUMEN
BACKGROUND: Oral squamous cell carcinoma (SCC) is associated with oral microbial dysbiosis. In this unique study, we compared pre- to post-treatment salivary microbiome in patients with SCC by 16S rRNA gene sequencing and examined how microbiome changes correlated with the expression of an anti-microbial protein. RESULTS: Treatment of SCC was associated with a reduction in overall bacterial richness and diversity. There were significant changes in the microbial community structure, including a decrease in the abundance of Porphyromonaceae and Prevotellaceae and an increase in Lactobacillaceae. There were also significant changes in the microbial community structure before and after treatment with chemoradiotherapy, but not with surgery alone. In patients treated with chemoradiotherapy alone, several bacterial populations were differentially abundant between responders and non-responders before and after therapy. Microbiome changes were associated with a change in the expression of DMBT1, an anti-microbial protein in human saliva. Additionally, we found that salivary DMBT1, which increases after treatment, could serve as a post-treatment salivary biomarker that links to microbial changes. Specifically, post-treatment increases in human salivary DMBT1 correlated with increased abundance of Gemella spp., Pasteurellaceae spp., Lactobacillus spp., and Oribacterium spp. This is the first longitudinal study to investigate treatment-associated changes (chemoradiotherapy and surgery) in the oral microbiome in patients with SCC along with changes in expression of an anti-microbial protein in saliva. CONCLUSIONS: The composition of the oral microbiota may predict treatment responses; salivary DMBT1 may have a role in modulating the oral microbiome in patients with SCC. After completion of treatment, 6 months after diagnosis, patients had a less diverse and less rich oral microbiome. Leptotrichia was a highly prevalent bacteria genus associated with disease. Expression of DMBT1 was higher after treatment and associated with microbiome changes, the most prominent genus being Gemella Video Abstract.
Asunto(s)
Carcinoma de Células Escamosas , Microbiota , Neoplasias de la Boca , Humanos , Neoplasias de la Boca/terapia , Estudios Longitudinales , ARN Ribosómico 16S/genética , Microbiota/genética , Saliva/microbiología , Bacterias/genética , Proteínas de Unión al Calcio , Proteínas de Unión al ADN , Proteínas Supresoras de TumorRESUMEN
BACKGROUND: This study assessed the relationship between non-participation in health check-ups and all-cause mortality and morbidity, considering socioeconomic status. METHODS: Healthy, middle-aged (35-54 years) working individuals who maintained either self-employed or employee status from 2006-2010 were recruited in this retrospective cohort study from the National Health Insurance Service in Korea. Health check-up participation was calculated as the sum of the number of health check-ups in 2007-2008 and 2009-2010. Adjusted hazard ratio (HR) and 95% confidence interval (CI) of all-cause mortality were estimated for each gender using multivariable Cox proportional hazard models, adjusting for age, income, residential area, and employment status. Interaction of non-participation in health check-ups and employment status on the risk of all-cause mortality was further analyzed. RESULTS: Among 4,267,243 individuals with a median 12-year follow-up (median age, 44; men, 74.43%), 89,030 (2.09%) died. The proportion (number) of deaths of individuals with no, one-time, and two-time participation in health check-ups was 3.53% (n = 47,496), 1.66% (n = 13,835), and 1.33% (n = 27,699), respectively. The association between health check-up participation and all-cause mortality showed a reverse J-shaped curve with the highest adjusted HR (95% CI) of 1.575 (1.541-1.611) and 1.718 (1.628-1.813) for men and women who did not attend any health check-ups, respectively. According to the interaction analysis, both genders showed significant additive and multiplicative interaction, with more pronounced additive interaction among women who did not attend health check-ups (relative excess risk due to interaction, 1.014 [0.871-1.158]). CONCLUSION: Our study highlights the significant reverse J-shaped association between health check-up participation and all-cause mortality. A pronounced association was found among self-employed individuals, regardless of gender.
Asunto(s)
Empleo , Disparidades Socioeconómicas en Salud , Persona de Mediana Edad , Humanos , Masculino , Femenino , Adulto , Estudios Retrospectivos , Riesgo , Estado de SaludRESUMEN
Background: Head and neck squamous cell carcinoma (HNSCC) is a class of heterogenous cancers involving the upper aerodigestive tract. We previously demonstrated the utility of a priori diet quality indices for predicting survival after an HNSCC diagnosis. The aim of this analysis was to evaluate the role of those a priori diet quality indices and proinflammatory cytokines in newly diagnosed HNSCC survivors. Methods: We analyzed cross-sectional data from a sample (n = 146; mean age 59.6 y; 79.3% male) from the University of Michigan Head and Neck Specialized Program of Research Excellence prospective longitudinal cohort study. Dietary intake was measured at pretreatment using a food frequency questionnaire. Serum samples were also collected at pretreatment. Covariate-adjusted proportional odds and logistic regression models were used to assess the relationship between 6 diet quality indices (Alternative Healthy Eating Index [AHEI]-2010, Alternate Mediterranean Diet, Dietary Approaches to Stop Hypertension [DASH], and 3 low-carbohydrate indices) and serum measures of a panel of 10 inflammatory cytokines and a cytokine summary composite score. Results: Higher scores on the AHEI-2010 and DASH diet quality indices were associated with higher odds of lower cytokine value scores for several cytokines and for the cytokine summary composite score (AHEI-2010-odds ratio [OR]: 1.55; 95% confidence interval [CI]: 1.10, 2.20; DASH-OR: 1.65; 95% CI 1.15, 2.36). Conclusions: Higher scores on the AHEI-2010 and DASH diet quality indices may be associated with lower proinflammatory cytokine levels in HNSCC survivors.
RESUMEN
DNA methylation is a vital early step in carcinogenesis. Most findings of aberrant DNA methylation in head and neck squamous cell carcinomas (HNSCC) are array based with limited coverage and resolution, and mainly explored by human papillomavirus (HPV) status, ignoring the high heterogeneity of this disease. In this study, we performed whole-genome bisulfite sequencing on a well-studied HNSCC cohort (n = 36) and investigated the methylation changes between fine-scaled HNSCC subtypes in relation to genomic instability, repetitive elements, gene expression, and key carcinogenic pathways. The previously observed hypermethylation phenotype in HPV-positive (HPV+) tumors compared with HPV-negative tumors was robustly present in the immune-strong (IMU) HPV+ subtype but absent in the highly keratinized (KRT) HPV+ subtype. Methylation levels of IMU tumors were significantly higher in repetitive elements, and methylation showed a significant correlation with genomic stability, consistent with the IMU subtype having more genomic stability and better prognosis. Expression quantitative trait methylation (cis-eQTM) analysis revealed extensive functionally-relevant differences, and differential methylation pathway analysis recapitulated gene expression pathway differences between subtypes. Consistent with their characteristics, KRT and HPV-negative tumors had high regulatory potential for multiple regulators of keratinocyte differentiation, which positively correlated with an expression-based keratinization score. Together, our findings revealed distinct mechanisms of carcinogenesis between subtypes in HPV+ HNSCC and uncovered previously ignored epigenomic differences and clinical implications, illustrating the importance of fine-scale subtype analysis in cancer. Significance: This study revealed that the previously observed hypermethylation of HPV(+) HNSCC is due solely to the IMU subtype, illustrating the importance of fine-scale subtype analysis in such a heterogeneous disease. Particularly, IMU has significantly higher methylation of transposable elements, which can be tested as a prognosis biomarker in future translational studies.
Asunto(s)
Neoplasias de Cabeza y Cuello , Infecciones por Papillomavirus , Humanos , Carcinoma de Células Escamosas de Cabeza y Cuello/genética , Metilación de ADN/genética , Infecciones por Papillomavirus/complicaciones , Carcinogénesis , Inestabilidad Genómica , Virus del Papiloma Humano , Neoplasias de Cabeza y Cuello/genéticaRESUMEN
Background: In recent years, interest in prognostic calculators for predicting patient health outcomes has grown with the popularity of personalized medicine. These calculators, which can inform treatment decisions, employ many different methods, each of which has advantages and disadvantages. Methods: We present a comparison of a multistate model (MSM) and a random survival forest (RSF) through a case study of prognostic predictions for patients with oropharyngeal squamous cell carcinoma. The MSM is highly structured and takes into account some aspects of the clinical context and knowledge about oropharyngeal cancer, while the RSF can be thought of as a black-box non-parametric approach. Key in this comparison are the high rate of missing values within these data and the different approaches used by the MSM and RSF to handle missingness. Results: We compare the accuracy (discrimination and calibration) of survival probabilities predicted by both approaches and use simulation studies to better understand how predictive accuracy is influenced by the approach to (1) handling missing data and (2) modeling structural/disease progression information present in the data. We conclude that both approaches have similar predictive accuracy, with a slight advantage going to the MSM. Conclusions: Although the MSM shows slightly better predictive ability than the RSF, consideration of other differences are key when selecting the best approach for addressing a specific research question. These key differences include the methods' ability to incorporate domain knowledge, and their ability to handle missing data as well as their interpretability, and ease of implementation. Ultimately, selecting the statistical method that has the most potential to aid in clinical decisions requires thoughtful consideration of the specific goals.
RESUMEN
Introduction: Coronavirus disease (COVID-19) is an infectious disease caused by the SARS-CoV-2-virus. COVID-19 has officially been declared as the latest in the list of pandemics by WHO at the start of 2020. This study investigates the associations among decrease in economic activity, gender, age, and psychological distress during the COVID-19 pandemic considering the economic status and education level of countries using multinational surveys. Methods: Online self-report questionnaires were administered in 15 countries which were spontaneously participate to 14,243 respondents in August 2020. Prevalence of decrease in economic activity and psychological distress was stratified by age, gender, education level, and Human Development Index (HDI). With 7,090 of female (49.8%), mean age 40.67, 5,734 (12.75%) lost their job and 5,734 (40.26%) suffered from psychological distress. Results: Associations among psychological distress and economic status, age, and gender was assessed using multivariate logistic regression, adjusted for country and education as random effects of the mixed model. We then measured the associations between HDI and age using multivariate logistic regression. Women had a higher prevalence of psychological distress than men with 1.067 Odds ratio, and younger age was significantly associated with decrease in economic activity for 0.998 for age increasing. Moreover, countries with lower HDI showed a higher prevalence of decrease in economic activity, especially at lower education levels. Discussion: Psychological distress due to COVID-19 revealed a significant association with decrease in economic activity, women, and younger age. While the proportion of decrease in economic activity population was different for each country, the degree of association of the individual factors was the same. Our findings are relevant, as women in high HDI countries and low education level in lower HDI countries are considered vulnerable. Policies and guidelines for both financial aid and psychological intervention are recommended.
Asunto(s)
COVID-19 , Distrés Psicológico , Masculino , Humanos , Femenino , SARS-CoV-2 , COVID-19/epidemiología , COVID-19/psicología , Pandemias , Encuestas y CuestionariosRESUMEN
The impact of the oral microbiome on head and neck cancer pathogenesis and outcomes requires further study. 16s rRNA was isolated and amplified from pre-treatment oral wash samples for 52 cases and 102 controls. The sequences were binned into operational taxonomic units (OTUs) at the genus level. Diversity metrics and significant associations between OTUs and case status were assessed. The samples were binned into community types using Dirichlet multinomial models, and survival outcomes were assessed by community type. Twelve OTUs from the phyla Firmicutes, Proteobacteria, and Acinetobacter were found to differ significantly between the cases and the controls. Beta-diversity was significantly higher between the cases than between the controls (p < 0.01). Two community types were identified based on the predominant sets of OTUs within our study population. The community type with a higher abundance of periodontitis-associated bacteria was more likely to be present in the cases (p < 0.01), in older patients (p < 0.01), and in smokers (p < 0.01). Significant differences between the cases and the controls in community type, beta-diversity, and OTUs indicate that the oral microbiome may play a role in HNSCC.
RESUMEN
BACKGROUND: Neighborhood deprivation is associated with both race and cancer incidence, but there is a need to better understand the effect of structural inequities on racial cancer disparities. The goal of this analysis was to evaluate the relationship between a comprehensive measure of neighborhood-level social disadvantage and cancer incidence within the racially diverse population of metropolitan Detroit. METHODS: We estimated breast, colorectal, lung, and prostate cancer incidence rates using Metropolitan Detroit Cancer Surveillance System and US decennial census data. Neighborhood socioeconomic disadvantage was measured by the Area Deprivation Index (ADI) using Census Bureau's American Community Survey data at the Public Use Microdata Areas (PUMA) level. Associations between ADI at time of diagnosis and cancer incidence were estimated using Poisson mixed-effects models adjusting for age and sex. Attenuation of race-incidence associations by ADI was quantified using the "mediation" package in R. RESULTS: ADI was inversely associated with incidence of breast cancer for both non-Hispanic White (NHW) and non-Hispanic Black (NHB) women (NHW: per-quartile RR = 0.92, 95% CI 0.88-0.96; NHB: per-quartile RR = 0.94, 95% CI 0.91-0.98) and with prostate cancer incidence only for NHW men (per-quartile RR = 0.94, 95% CI 0.90-0.97). ADI was positively associated with incidence of lung cancer for NHWs and NHBs (NHW: per-quartile RR = 1.12, 95% CI 1.04-1.21; NHB: per-quartile RR = 1.37, 95% CI 1.25-1.51) and incidence of colorectal cancer (CRC) only among NHBs (per-quartile RR = 1.11, 95% CI 1.02-1.21). ADI significantly attenuated the relationship between race and hormone receptor positive, HER2-negative breast cancer (proportion attenuated = 8.5%, 95% CI 4.1-16.6%) and CRC cancer (proportion attenuated = 7.3%, 95% CI 3.7 to 12.8%), and there was a significant interaction between race and ADI for lung (interaction RR = 1.22, p < 0.0001) and prostate cancer (interaction RR = 1.09, p = 0.00092). CONCLUSIONS: Area-level socioeconomic disadvantage is associated with risk of common cancers in a racially diverse population and plays a role in racial differences in cancer incidence.
Asunto(s)
Neoplasias de la Mama , Neoplasias de la Próstata , Masculino , Humanos , Incidencia , Disparidades Socioeconómicas en Salud , Etnicidad , Factores SocioeconómicosRESUMEN
PURPOSE: Perineural invasion (PNI) in oral cavity squamous cell carcinoma (OSCC) is associated with poor survival. Because of the risk of recurrence, patients with PNI receive additional therapies after surgical resection. Mechanistic studies have shown that nerves in the tumor microenvironment promote aggressive tumor growth. Therefore, in this study, we evaluated whether nerve density (ND) influences tumor growth and patient survival. Moreover, we assessed the reliability of artificial intelligence (AI) in evaluating ND. EXPERIMENTAL DESIGN: To investigate whether increased ND in OSCC influences patient outcome, we performed survival analyses. Tissue sections of OSCC from 142 patients were stained with hematoxylin and eosin and IHC stains to detect nerves and tumor. ND within the tumor bulk and in the adjacent 2 mm was quantified; normalized ND (NND; bulk ND/adjacent ND) was calculated. The impact of ND on tumor growth was evaluated in chick chorioallantoic-dorsal root ganglia (CAM-DRG) and murine surgical denervation models. Cancer cells were grafted and tumor size quantified. Automated nerve detection, applying the Halo AI platform, was compared with manual assessment. RESULTS: Disease-specific survival decreased with higher intratumoral ND and NND in tongue SCC. Moreover, NND was associated with worst pattern-of-invasion and PNI. Increasing the number of DRG, in the CAM-DRG model, increased tumor size. Reduction of ND by denervation in a murine model decreased tumor growth. Automated and manual detection of nerves showed high concordance, with an F1 score of 0.977. CONCLUSIONS: High ND enhances tumor growth, and NND is an important prognostic factor that could influence treatment selection for aggressive OSCC. See related commentary by Hondermarck and Jiang, p. 2342.
Asunto(s)
Carcinoma de Células Escamosas , Neoplasias de Cabeza y Cuello , Neoplasias de la Boca , Humanos , Animales , Ratones , Inteligencia Artificial , Reproducibilidad de los Resultados , Invasividad Neoplásica , Neoplasias de la Boca/patología , Carcinoma de Células Escamosas/patología , Carcinoma de Células Escamosas de Cabeza y Cuello , Microambiente TumoralRESUMEN
BACKGROUND: Racial segregation is linked to poorer neighborhood quality and adverse health conditions among minorities, including worse cancer outcomes. We evaluated relationships between race, neighborhood social disadvantage, and cancer survival. METHODS: We calculated overall and cancer-specific survival for 11,367 non-Hispanic Black (NHB) and 29,481 non-Hispanic White (NHW) individuals with breast, colorectal, lung, or prostate cancer using data from the Metropolitan Detroit Cancer Surveillance System. The area deprivation index (ADI) was used to measure social disadvantage at the census block group level, where higher ADI is associated with poorer neighborhood factors. Associations between ADI and survival were estimated using Cox proportional hazards mixed-effects models accounting for geographic grouping and adjusting for demographic and clinical factors. RESULTS: Increasing ADI quintile was associated with increased overall mortality for all four cancer sites in multivariable-adjusted models. Stratified by race, these associations remained among breast (NHW: HR = 1.16, P < 0.0001; NHB: HR = 1.20, P < 0.0001), colorectal (NHW: HR = 1.11, P < 0.0001; NHB: HR = 1.09, P = 0.00378), prostate (NHW: HR = 1.18, P < 0.0001; NHB: HR = 1.18, P < 0.0001), and lung cancers (NHW: HR = 1.06, P < 0.0001; NHB: HR = 1.07, P = 0.00177). Cancer-specific mortality estimates were similar to overall mortality. Adjustment for ADI substantially attenuated the effects of race on mortality for breast [overall proportion attenuated (OPA) = 47%, P < 0.0001; cancer-specific proportion attenuated (CSPA) = 37%, P < 0.0001] prostate cancer (OPA = 51%, P < 0.0001; CSPA = 56%, P < 0.0001), and colorectal cancer (OPA = 69%, P = 0.032; CSPA = 36%, P = 0.018). CONCLUSIONS: Area-level socioeconomic disadvantage is related to cancer mortality in a racially diverse population, impacting racial differences in cancer mortality. IMPACT: Understanding the role of neighborhood quality in cancer survivorship could improve community-based intervention practices.
Asunto(s)
Neoplasias , Disparidades Socioeconómicas en Salud , Humanos , Etnicidad , Factores Socioeconómicos , Neoplasias/mortalidadRESUMEN
Background: Leptospirosis is an infectious disease caused by a pathogenic Leptospira species transmitted directly or indirectly from animals to humans. It is endemic in Southeast Asia in several countries, including Indonesia and Thailand. Therefore, this study aimed to determine the effect of community behavior on the incidence of leptospirosis in West Jakarta in 2019. Methods: The study used a case-control design, and data were obtained from the West Jakarta Health Office. The sample included 140 respondents, consisting of 70 leptospirosis patients (cases) and 70 participants who did not suffer from the disease (controls) in a 1:1 ratio. Results: In the bivariate analysis, there were significant effects on leptospirosis incidence from knowledge (odds ratio [OR] = 18.789), occupation (OR = 31.875), injury history (OR = 20.842), and recreation (OR = 0.294). Multivariate analysis showed significant effects based on occupation, present wounds, and recreation records. Occupation was a dominant factor in leptospirosis in West Jakarta (OR 54.116: 95% confidence interval: 4.435-660.372). Conclusion: The dominant factors for leptospirosis were risky occupations, followed by a history of injuries.
Asunto(s)
Leptospira , Leptospirosis , Humanos , Animales , Indonesia/epidemiología , Incidencia , Leptospirosis/epidemiología , Leptospirosis/veterinaria , Asia SudorientalRESUMEN
INTRODUCTION: Financial toxicity (FT) is a growing concern among cancer survivors that adversely affects the quality of life and survival. Individuals diagnosed with aggressive cancers are often at a greater risk of experiencing FT. The objectives of this study were to estimate FT among prostate cancer (PCa) survivors after 10-15 years of diagnosis, assess the relationship between PCa aggressiveness at diagnosis and FT, and examine whether current cancer treatment status mediates the relationship between PCa aggressiveness and FT. METHODS: PCa patients enrolled in the North Carolina-Louisiana Prostate Cancer Project (PCaP) were recontacted for long-term follow-up. The prevalence of FT in the PCaP cohort was estimated. FT was estimated using the COmprehensive Score for Financial Toxicity, a validated measure of FT. The direct effect of PCa aggressiveness and an indirect effect through current cancer treatment on FT was examined using causal mediation analysis. RESULTS: More than one-third of PCa patients reported experiencing FT. PCa aggressiveness was significantly independently associated with high FT; high aggressive PCa at diagnosis had more than twice the risk of experiencing FT than those with low or intermediate aggressive PCa (adjusted odds ratio [aOR] = 2.13, 95% CI = 1.14-3.96). The proportion of the effect of PCa aggressiveness on FT, mediated by treatment status, was 10%, however, the adjusted odds ratio did not indicate significant evidence of mediation by treatment status (aOR = 1.05, 95% CI = 0.95-1.20). CONCLUSIONS: Aggressive PCa was associated with high FT. Future studies should collect more information about the characteristics of men with high FT and identify additional risk factors of FT.
Asunto(s)
Estrés Financiero , Neoplasias de la Próstata , Calidad de Vida , Humanos , Masculino , Louisiana , North Carolina/epidemiología , Neoplasias de la Próstata/epidemiología , Neoplasias de la Próstata/psicologíaRESUMEN
Liver cancer is the most common cancer in Northern Thailand, mainly due to the dietary preference for raw fish, which can lead to infection by the parasite, O. viverrini, a causal agent of cholangiocarcinoma. We conducted a temporal trend analysis of cross-sectional incidence rates of liver cancer in Lampang, Northern Thailand. Liver cancer data from 1993-2012 were extracted from Lampang Cancer Registry. The multiple imputation by chained equations method was used to impute missing histology data. Imputed data were analyzed using Joinpoint and age-period-cohort (APC) models to characterize the incidence rates by gender, region, and histology, considering hepatocellular carcinoma (HCC) and cholangiocarcinoma (CCA). We observed a significant annual increase in CCA incidence and a considerable decrease in HCC incidence for both genders in Lampang. The APC analysis suggested that CCA incidence rates were higher in older ages, younger cohorts, and later years of diagnosis. In contrast, HCC incidence rates were higher in older generations and earlier years of diagnosis. Further studies of potential risk factors of CCA are needed to better understand and address the increasing burden of CCA in Lampang. Our findings may help to draw public attention to cholangiocarcinoma prevention and control in Northern Thailand.
Asunto(s)
Neoplasias de los Conductos Biliares , Carcinoma Hepatocelular , Colangiocarcinoma , Neoplasias Hepáticas , Animales , Neoplasias de los Conductos Biliares/epidemiología , Neoplasias de los Conductos Biliares/parasitología , Conductos Biliares Intrahepáticos , Carcinoma Hepatocelular/epidemiología , Colangiocarcinoma/diagnóstico , Colangiocarcinoma/epidemiología , Colangiocarcinoma/parasitología , Estudios Transversales , Femenino , Humanos , Incidencia , Neoplasias Hepáticas/epidemiología , Masculino , Tailandia/epidemiologíaRESUMEN
PURPOSE: Perineural invasion (PNI), a common occurrence in oral squamous cell carcinomas, is associated with poor survival. Consequently, these tumors are treated aggressively. However, diagnostic criteria of PNI vary and its role as an independent predictor of prognosis has not been established. To address these knowledge gaps, we investigated spatial and transcriptomic profiles of PNI-positive and PNI-negative nerves. EXPERIMENTAL DESIGN: Tissue sections from 142 patients were stained with S100 and cytokeratin antibodies. Nerves were identified in two distinct areas: tumor bulk and margin. Nerve diameter and nerve-to-tumor distance were assessed; survival analyses were performed. Spatial transcriptomic analysis of nerves at varying distances from tumor was performed with NanoString GeoMx Digital Spatial Profiler Transcriptomic Atlas. RESULTS: PNI is an independent predictor of poor prognosis among patients with metastasis-free lymph nodes. Patients with close nerve-tumor distance have poor outcomes even if diagnosed as PNI negative using current criteria. Patients with large nerve(s) in the tumor bulk survive poorly, suggesting that even PNI-negative nerves facilitate tumor progression. Diagnostic criteria were supported by spatial transcriptomic analyses of >18,000 genes; nerves in proximity to cancer exhibit stress and growth response changes that diminish with increasing nerve-tumor distance. These findings were validated in vitro and in human tissue. CONCLUSIONS: This is the first study in human cancer with high-throughput gene expression analysis in nerves with striking correlations between transcriptomic profile and clinical outcomes. Our work illuminates nerve-cancer interactions suggesting that cancer-induced injury modulates neuritogenesis, and supports reclassification of PNI based on nerve-tumor distance rather than current subjective criteria.
Asunto(s)
Neoplasias de Cabeza y Cuello , Neoplasias de la Boca , Neoplasias de Cabeza y Cuello/patología , Humanos , Queratinas , Neoplasias de la Boca/genética , Neoplasias de la Boca/patología , Invasividad Neoplásica/genética , Invasividad Neoplásica/patología , Estadificación de Neoplasias , Nervios Periféricos/patología , Pronóstico , Estudios Retrospectivos , TranscriptomaRESUMEN
Despite the overall decreasing incidence, nasopharyngeal cancer (NPC) continues to cause a significant health burden among Asian Americans (AAs), who are a fast-growing but understudied heterogeneous racial group in the United States. We aimed to examine the racial/ethnic disparities in NPC incidence, treatment, and mortality with a specific focus on AA subgroups. NPC patients aged ≥15 years were obtained from the Surveillance, Epidemiology, and End Results (SEER) 18 (1975-2018). AAs were divided into Chinese, Filipino, Vietnamese, Hawaiian, Japanese, Laotian, Korean, Cambodian, Indian/Pakistani and other Asian/Pacific Islanders (APIs). Age-adjusted incidence was calculated using the SEER*Stat software. Cox proportional and Fine-Gray subdistribution hazard models were used to calculate overall and cause-specific mortalities after adjusting for confounders. Among the total 11 964 NPC cases, 18.4% were Chinese, 7.7% Filipino, 5.0% Vietnamese, 1.2% Hawaiian, 1.0% Japanese, 0.8% Laotian, 0.8% Korean, 0.6% Cambodian, 0.5% Indian/Pakistani and 4.4% other APIs. Laotians had the highest age-adjusted NPC incidence (9.21 per 100 000), which was 18.04 times higher than it in non-Hispanic Whites (NHWs). Chinese and Filipinos observed lower overall mortalities, however, Chinese saw increased NPC-specific mortality than NHWs. Disparities in mortality were also found across different histology subtypes. This is the first and largest study examining the NPC incidence and outcomes in AA subgroups. The significant disparities of NPC within AAs underline the importance of adequate AA-subgroup sample size in future studies to understand the prognostic role of ethnicity in NPC and advocate more ethnically and culturally tailored cancer prevention and care delivery.
Asunto(s)
Asiático , Neoplasias Nasofaríngeas , Etnicidad , Humanos , Carcinoma Nasofaríngeo , Grupos Raciales , Estados Unidos/epidemiología , Población BlancaRESUMEN
Aberrant global DNA methylation status is a known biomarker for increased disease risk, especially cancer. There is little published data on the association between toxic and essential metal mixtures and global DNA methylation in electronic waste (e-waste) workers. We aimed to establish the association between toxic and essential metals in blood and the effect of their interactions on global DNA methylation among e-waste recyclers and a reference group in Ghana. We used ICP-MS to measure the level of five metals (Se, Zn, Mn, Cd, and Pb) in the blood of 100 e-waste workers and 51 controls. We quantified blood DNA methylation levels of LINE-1 as an indicator of global DNA methylation. Cd, Mn, and Se levels were significantly higher in the reference group than in e-waste workers. Only Pb was significantly higher in the e-waste workers compared to the controls. Our linear regression analysis results showed a significant inverse association between Zn and LINE-1 DNA methylation (ßZn = - 0.912; 95% CI, - 1.512, - 0.306; p = 0.003) which corresponds to a 0.009 decrease in %LINE-1 methylation (95% CI, - 0.015, - 0.003; p = 0.003) for a 1% increase in Zn concentration. Potential interactions between Cd and Zn on global DNA methylation were observed. In summary, co-exposure to toxic and essential metals is associated with global (LINE-1) DNA methylation.
Asunto(s)
Residuos Electrónicos , Metales Pesados , Cadmio/análisis , Metilación de ADN , Residuos Electrónicos/análisis , Ghana , Humanos , Plomo/análisis , Metales Pesados/análisis , ReciclajeRESUMEN
No studies, to date, have scrutinized the role of a priori dietary patterns on prognosis following a head and neck squamous cell carcinoma (HNSCC) diagnosis. The purpose of this analysis was to evaluate the associations between adherence to six a priori defined diet quality indices (including AHEI-2010, aMED, DASH, and three low-carbohydrate indices) throughout the first 3 years of observation and all-cause and cancer-specific mortalities in 468 newly diagnosed HNSCC patients from the University of Michigan Head and Neck Specialized Program of Research Excellence (UM-SPORE). The dietary intake data were measured using a food frequency questionnaire administered at three annual time points commencing at study entry. Deaths and their causes were documented throughout the study using various data sources. Marginal structural Cox proportional hazards models were used to evaluate the role of diet quality, as a time-varying covariate, on mortality. There were 93 deaths from all causes and 74 cancer-related deaths adjudicated throughout the observation period. There was a strong inverse association between adherence to the AHEI-2010, all-cause mortality (HR Q5-Q1 :0.07, 95% CI:0.01-0.43, p trend:0.04), and cancer-specific mortality (HR Q5-Q1 :0.15, 95% CI:0.02-1.07, p trend:0.04). Other more modest associations were noted for the low-carbohydrate indices. In sum, higher adherence to the AHEI-2010 and a plant-based low-carbohydrate index throughout the first 3 years since diagnosis may bolster survival and prognosis in newly diagnosed patients with HNSCC.