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BACKGROUND: Stroma AReactive Invasion Front Areas (SARIFA) is a recently identified haematoxylin & eosin (H&E)based histopathologic biomarker in gastrointestinal cancers, including colorectal cancer (CRC), defined as direct contact between tumour cells and adipocytes at the tumour invasion front. The current study aimed at validating the prognostic relevance of SARIFA in a large population-based CRC series as well as at investigating the relationship between SARIFA-status and previously established Warburg-subtypes, both surrogates of the metabolic state of the tumour cells. METHODS: SARIFA-status (positive versus negative) was determined on H&E slides of 1,727 CRC specimens. Warburg-subtype (high versus moderate versus low) data was available from our previous study. The associations between SARIFA-status, Warburg-subtype, clinicopathological characteristics and CRC-specific as well as overall survival were investigated. RESULTS: 28.7% (n=496) CRC were SARIFA-positive. SARIFA-positivity was associated with more advanced disease stage, higher pT category, and more frequent lymph node involvement (all p<0.001). SARIFA-positivity was more common in Warburg-high CRC. 44.2% (n=219) of SARIFA-positive CRCs were Warburg-high compared to 22.8% (n=113) being Warburg-low and 33.1% (n=164) being Warburg-moderate (p<0.001). In multivariable-adjusted analysis, patients with SARIFA-positive CRCs had significantly poorer CRC-specific (HRCRC-specific 1.65; 95% CI 1.41-1.93) and overall survival (HRoverall survival 1.46; 95% CI 1.28-1.67) independent of clinically known risk factors and independent of Warburg-subtype. Combining the SARIFA-status and the Warburg-subtype to a combination score (SARIFA-negative/Warburg-high versus SARIFA-positive/Warburg-low versus SARIFA-positive/Warburg-high, and so on) did not improve the survival prediction compared to the use of SARIFA-status alone (SARIFA-negative + Warburg-high: HRCRC-specific 1.08; 95% CI 0.84-1.38; SARIFA-positive + Warburg-low: HRCRC-specific 1.79; 95% CI 1.32-2.41; SARIFA-positive + Warburg-high: HRCRC-specific 1.58; 95% CI 1.23-2.04). CONCLUSIONS: Our current study is the by far largest external validation of SARIFA-positivity as a novel independent negative prognostic H&E-based biomarker in CRC. In addition, our study shows that SARIFA-positivity is associated with the Warburg-high subtype. Further research is warranted to provide a more mechanistic understanding of the underlying tumour biology. Based on our data, we conclude SARIFA-status should be implemented in pathologic routine practice to stratify CRC patients.
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BACKGROUND: Long-term energy balance-related factors (i.e. lifestyle and physiological factors that influence the equilibrium between energy intake and energy expenditure over an extended period) like body mass index (BMI) are linked to colorectal cancer (CRC) risk, but their impact on CRC survival is unclear. We explored associations between these long-term energy balance-related factors and survival, and examined potential differences across metabolic Warburg-subtypes. METHODS: Associations between long-term energy balance-related factors and survival in the total series of CRC patients (n=2,347) obtained from the prospective Netherlands Cohort Study, as well as according to Warburg-subtype (Warburg-low: n=652, Warburg-moderate: n=802, Warburg-high: n=797), were investigated using Cox regression analysis. RESULTS: Among the long-term energy balance-related factors studied, only increasing pre-diagnostic BMI was associated with a borderline significant poorer overall survival in CRC patients (HR5kg/m2 1.07; 95%CI 0.99-1.15). Stratified analyses showed that pre-diagnostic weight gain (HR5kg 1.06; 95%CI 1.00-1.12), and potentially increased height (HR5cm 1.04; 95%CI 0.98-1.11), were associated with poor overall survival only in patients with Warburg-high CRC. Increasing pre-diagnostic BMI was associated with poor survival only in patients with Warburg-moderate CRC (CRC-specific: HR5kg/m2 1.12; 95%CI 0.96-1.32, overall: HR5kg/m2 1.20; 95%CI 1.05-1.36). No consistent patterns were observed across energy-restriction proxies. CONCLUSIONS: Maintaining a healthy pre-diagnostic BMI may be beneficial for CRC survival. Moreover, associations between pre-diagnostic BMI, weight change, early-life energy restriction, height and CRC survival differed according to Warburg-subtype. IMPACT: Understanding the biological pathways involved in associations between energy balance-related factors and CRC survival could help refine prevention strategies in the future.
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OBJECTIVES: Previous studies found no or weak positive associations between height and lung cancer (LC) risk, with differences between sexes. Few studies stratified the association by smoking status and LC subtype. This prospective study investigated the association between height and risks of overall LC and LC subtypes (i.e., adenocarcinoma, squamous cell carcinoma, small cell carcinoma, large cell carcinoma) in Dutch men and women, with comprehensive adjustment for smoking, and stratified by smoking status. MATERIALS AND METHODS: Data originate from 120,852 Dutch participants aged 55-69 in 1986 in the Netherlands Cohort Study. Self-reported height and potential confounders were collected at baseline. After 20.3 years of follow-up, 3318 LC cases (2765 men; 553 women) and 4314 subcohort members were included in the multivariable Cox regression analysis. RESULTS: There were no significant associations between height and risks of overall LC and LC subtypes in men and women, except for an increased adenocarcinoma risk in taller women (HRquartile4 vs quartile1=1.62, 95% CI: 1.02-2.55, Ptrend=0.031). This positive association was borderline statistically significant in female current smokers only when stratifying on smoking status. No interaction by smoking status was shown in women for any LC risk. In men, smoking modified the association between height and risks of overall LC, large cell and squamous cell carcinoma, with the p-values for interaction of 0.037, 0.007 and 0.050, respectively. CONCLUSION: Positive associations between height and LC subtypes were predominantly seen in smokers. Further studies should focus on LC subtypes and stratify the association by smoking status.
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Over the last years, insights in the cancer neuroscience field increased rapidly and a potential role for neurons in colorectal carcinogenesis has been recognized. However, knowledge on the neuronal distribution, subtypes, origin and associations with clinicopathological characteristics in human studies is sparse. In this study, colorectal tumor tissues from the Netherlands Cohort Study on diet and cancer (n=490) and an in-cohort validation population (n=529) were immunohistochemically stained for the pan-neuronal markers neurofilament (NF) and protein gene product 9.5 (PGP9.5) to study the association between neuronal marker expression and clinicopathological characteristics. In addition, tumor and healthy colon tissue were stained for neuronal subtype markers and their immunoreactivity in colorectal cancer (CRC) stroma was analyzed. NF and PGP9.5 positive nerve fibers were found within the tumor stroma and were mostly characterized by the neuronal subtype markers vasoactive intestinal protein (VIP) and neuronal nitric oxide synthase (nNOS), suggesting that inhibitory neurons are the most prominent neuronal subtype in CRC. NF and PGP9.5 protein expression were not consistently associated with tumor stage, sublocation, differentiation grade and median survival. NF immunoreactivity was associated with a worse CRC-specific survival in the study cohort (p=0.025), independent of other prognostic factors (HR=2.31; 95% CI 1.33-4.03; p=0.003), but these results were not observed in the in-cohort validation group. PGP9.5 on the other hand, was associated with a worse CRC-specific survival in the in-cohort validation (p=0.046) but not in the study population. This effect disappeared in multivariate analyses (HR=0.81; 95% CI 0.50-1.32; p=0.393) indicating that this effect was dependent on other prognostic factors. This study demonstrates that the tumor stroma of CRC patients mainly harbors inhibitory neurons and that NF as a single marker is significantly associated with a poorer CRC-specific survival in the study cohort but necessitates future validation.
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INTRODUCTION: It is crucial to monitor changes in body weight and physical activity (PA) to understand if short-term effects of COVID-19 pandemic have had implications over time. METHODS: This longitudinal study is based on data from 4,831 Italians aged 18-74 years interviewed during the first phase of COVID-19 pandemic (April-May 2020) and two years later (February-March 2022). Changes in body weight and PA were assessed through multivariable analyses in association with socio-demographic and psychological characteristics. RESULTS: Over the two years, 17.4% reported a weight gain of at least 5 kg and 32.8% a decreased PA by at least 4 hours per week. Weight gain and decreased PA were more frequent in participants from the less wealthy areas, with lower educational level and those who reported a worsening in mental health. CONCLUSIONS: After two years from the start of the pandemic, in Italy we observed a trend toward a renormalization of body weight and PA. The segments of the population mostly affected by the pandemic are subjects with more disadvantaged socio-economic status and with an impaired mental health.
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COVID-19 , Ejercicio Físico , Pandemias , Aumento de Peso , Humanos , COVID-19/epidemiología , COVID-19/psicología , Persona de Mediana Edad , Italia/epidemiología , Adulto , Masculino , Femenino , Anciano , Adulto Joven , Adolescente , Estudios Prospectivos , Estudios Longitudinales , Estudios de Cohortes , Factores Socioeconómicos , SARS-CoV-2RESUMEN
BACKGROUND: Despite the high frequency of tinnitus and its impact on wellbeing, little is known about its economic burden and no data to our knowledge are available on out-of-pocket (OOP) expenses. METHODS: In 2022 a survey was conducted on OOP costs of tinnitus. We enrolled 679 participants with slight, moderate and severe tinnitus in Italy, United Kingdom, Netherlands, Germany and Spain. We estimated annual OOP expenses for tinnitus-related healthcare visits, treatments, medications and alternative medicine practices. Prevalence of tinnitus in the general population, obtained from a representative survey we conducted in Europe in 2017-2018, was used to generalise costs for people with any tinnitus at the national level. RESULTS: OOP expenses were 368 (95% confidence intervals (CI), 78-690), 728 (95% CI, 316-1,288), and 1,492 (95% CI, 760-2,688) for slight, moderate, and severe tinnitus, respectively, with annual expenditure of 565 for people with any tinnitus: 209 for healthcare visits, 93 for treatments, 16 for drugs, 64 for hearing supporting systems and 183 for acupuncture, homeopathy and osteopathy. Individuals with slight, moderate, and severe tinnitus expressed a willingness to invest 1.6, 4.3, and 7.0 times their monthly income, respectively, to achieve complete relief from tinnitus. CONCLUSIONS: This study offers for the first time insights into the OOP expenses incurred by individuals with tinnitus. OOP expenses exhibited substantial variations based on severity status, accounting for more than 17 thousand million in the countries considered. In terms of financial burden, these findings align tinnitus to the recognised leading disabilities, including back pain and migraine.
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BACKGROUND: Evidence of an association between dietary fiber intake and risk of advanced and aggressive forms of prostate cancer (PC) and PC mortality is limited. OBJECTIVE: The aim of this study was to examine associations between intakes of dietary fiber overall and by food source and risk of advanced and aggressive forms of PC. DESIGN: The study design was a pooled analysis of the primary data from 15 cohorts in 3 continents. Baseline dietary fiber intake was assessed using a validated food frequency questionnaire or diet history in each study. PARTICIPANTS/SETTING: There were 842 149 men followed for up to 9 to 22 years between 1985 and 2009 across studies. MAIN OUTCOME MEASURES: The primary outcome measures were advanced (stage T4, N1, or M1 or PC mortality), advanced restricted (excluded men with missing stage and those with localized PC who died of PC), and high-grade PC (Gleason score ≥8 or poorly differentiated/undifferentiated) and PC mortality. STATISTICAL ANALYSIS PERFORMED: Study-specific multivariable hazard ratios (MVHR) were calculated using Cox proportional hazards regression and pooled using random effects models. RESULTS: Intake of dietary fiber overall, from fruits, and from vegetables was not associated with risk of advanced (n = 4863), advanced restricted (n = 2978), or high-grade PC (n = 9673) or PC mortality (n = 3097). Dietary fiber intake from grains was inversely associated with advanced PC (comparing the highest vs lowest quintile, MVHR 0.84; 95% CI 0.76-0.93), advanced restricted PC (MVHR 0.85; 95% CI 0.74-0.97), and PC mortality (MVHR 0.78; 95% CI 0.68-0.89); statistically significant trends were noted for each of these associations (P ≤ .03), and a null association was observed for high-grade PC for the same comparison (MVHR 1.00; 95% CI 0.93-1.07). The comparable results were 1.06 (95% CI 1.01-1.10; P value, test for trend = .002) for localized PC (n = 35,199) and 1.05 (95% CI 0.99-1.11; P value, test for trend = .04) for low/intermediate grade PC (n = 34 366). CONCLUSIONS: Weak nonsignificant associations were observed between total dietary fiber intake and risk of advanced forms of PC, high-grade PC, and PC mortality. High dietary fiber intake from grains was associated with a modestly lower risk of advanced forms of PC and PC mortality.
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Meta-analyses have shown modest positive associations between diabetes mellitus (DM) and bladder cancer risk, but results are heterogeneous. This might be due to lack of distinction between bladder cancer subtypes, between sexes, and possibly between Type 2 and Type 1 DM (T2DM and T1DM). The relationship of T2DM (and secondarily T1DM) characteristics with risk of bladder cancer subtypes (invasive versus noninvasive) was investigated in the Netherlands Cohort Study. In 1986, 120,852 men and women aged 55-69 years provided information on DM and lifestyle data. After 20.3 years of follow-up, multivariable case-cohort analyses were based on 1020 invasive and 1088 noninvasive bladder cancer cases, and 4267 subcohort members with complete data on DM and confounders. While T2DM was not associated with noninvasive bladder cancer, it was statistically significantly associated with invasive bladder cancer risk: the multivariable-adjusted was HR = 1.57 (95% CI 1.04-2.37), comparing participants with T2DM versus without DM. The association was only significant in women, and women showed a stronger association [HR = 2.19 (95% CI 1.10-4.34)] between T2DM and invasive bladder cancer than men [HR = 1.42 (95% CI 0.88-2.30)]; interaction by sex was nonsignificant. Associations were stronger positive in those whose age at diagnosis of T2DM was 55+ years, and in those diagnosed with T2DM less than five years before baseline. T2DM participants using antidiabetic medication had higher invasive bladder cancer risk than those without DM. Exploratory age-sex-adjusted analyses suggested a positive association between T1DM and invasive bladder cancer, but this was based on few cases. These findings suggest that T2DM and possibly T1DM are positively associated with invasive bladder cancer risk.
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Diabetes Mellitus Tipo 2 , Neoplasias de la Vejiga Urinaria , Humanos , Neoplasias de la Vejiga Urinaria/epidemiología , Masculino , Femenino , Persona de Mediana Edad , Anciano , Países Bajos/epidemiología , Diabetes Mellitus Tipo 2/epidemiología , Diabetes Mellitus Tipo 2/complicaciones , Factores de Riesgo , Estudios de Cohortes , Diabetes Mellitus Tipo 1/epidemiología , Diabetes Mellitus Tipo 1/complicaciones , Factores Sexuales , Invasividad NeoplásicaRESUMEN
BACKGROUND: The incidence rates of endometrial cancer are increasing, which may partly be explained by the rising prevalence of obesity, an established risk factor for endometrial cancer. Hypertension, another component of metabolic syndrome, is also increasing in prevalence, and emerging evidence suggests that it may be associated with the development of certain cancers. The role of hypertension independent of other components of metabolic syndrome in the etiology of endometrial cancer remains unclear. In this study, we evaluated hypertension as an independent risk factor for endometrial cancer and whether this association is modified by other established risk factors. METHODS: We included 15,631 endometrial cancer cases and 42,239 controls matched on age, race, and study-specific factors from 29 studies in the Epidemiology of Endometrial Cancer Consortium. We used multivariable unconditional logistic regression models to estimate ORs and 95% confidence intervals (CI) to evaluate the association between hypertension and endometrial cancer and whether this association differed by study design, race/ethnicity, body mass index, diabetes status, smoking status, or reproductive factors. RESULTS: Hypertension was associated with an increased risk of endometrial cancer (OR, 1.14; 95% CI, 1.09-1.19). There was significant heterogeneity by study design (Phet < 0.01), with a stronger magnitude of association observed among case-control versus cohort studies. Stronger associations were also noted for pre-/perimenopausal women and never users of postmenopausal hormone therapy. CONCLUSIONS: Hypertension is associated with endometrial cancer risk independently from known risk factors. Future research should focus on biologic mechanisms underlying this association. IMPACT: This study provides evidence that hypertension may be an independent risk factor for endometrial cancer.
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Neoplasias Endometriales , Hipertensión , Humanos , Femenino , Neoplasias Endometriales/epidemiología , Factores de Riesgo , Hipertensión/epidemiología , Persona de Mediana Edad , Estudios de Casos y Controles , Anciano , Adulto , IncidenciaRESUMEN
BACKGROUND: There is debate over whether the glycaemic index of foods relates to chronic disease. We aimed to assess the associations between glycaemic index (GI) and glycaemic load (GL) and type 2 diabetes, cardiovascular disease, diabetes-related cancers, and all-cause mortality. METHODS: We did a meta-analysis of large cohorts (≥100â000 participants) identified from the Richard Doll Consortium. We searched the Cochrane Library, MEDLINE, PubMed, Embase, Web of Science, and Scopus for cohorts that prospectively examined associations between GI or GL and chronic disease outcomes published from database inception to Aug 4, 2023. Full-article review and extraction of summary estimates data were conducted by three independent reviewers. Primary outcomes were incident type 2 diabetes, total cardiovascular disease (including mortality), diabetes-related cancers (ie, bladder, breast, colorectal, endometrial, hepatic, pancreatic, and non-Hodgkin lymphoma), and all-cause mortality. We assessed comparisons between the lowest and highest quantiles of GI and GL, adjusting for dietary factors, and pooling their most adjusted relative risk (RR) estimates using a fixed-effects model. We also assessed associations between diets high in fibre and whole grains and the four main outcomes. The study protocol is registered with PROSPERO, CRD42023394689. FINDINGS: From ten prospective large cohorts (six from the USA, one from Europe, two from Asia, and one international), we identified a total of 48 studies reporting associations between GI or GL and the outcomes of interest: 34 (71%) on various cancers, nine (19%) on cardiovascular disease, five (10%) on type 2 diabetes, and three (6%) on all-cause mortality. Consumption of high GI foods was associated with an increased incidence of type 2 diabetes (RR 1·27 [95% CI 1·21-1·34]; p<0·0001), total cardiovascular disease (1·15 [1·11-1·19]; p<0·0001), diabetes-related cancer (1·05 [1·02-1·08]; p=0·0010), and all-cause mortality (1·08 [1·05-1·12]; p<0·0001). Similar associations were seen between high GL and diabetes (RR 1·15 [95% CI 1·09-1·21]; p<0·0001) and total cardiovascular disease (1·15 [1·10-1·20]; p<0·0001). Associations between diets high in fibre and whole grains and the four main outcomes were similar to those for low GI diets. INTERPRETATION: Dietary recommendations to reduce GI and GL could have effects on health outcomes that are similar to outcomes of recommendations to increase intake of fibre and whole grain. FUNDING: Banting and Best and the Karuna Foundation.
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Enfermedades Cardiovasculares , Diabetes Mellitus Tipo 2 , Carga Glucémica , Neoplasias , Humanos , Índice Glucémico , Diabetes Mellitus Tipo 2/epidemiología , Enfermedades Cardiovasculares/epidemiología , Estudios Prospectivos , Neoplasias/epidemiología , Dieta , Enfermedad Crónica , Carbohidratos de la Dieta , Factores de RiesgoRESUMEN
Data on the role of circadian related factors in the etiology of endometrial cancer are scarce. We collected individual data on night shift work or daily sleep duration from 7,207 cases and 22,027 controls participating in 11 studies from the Epidemiology of Endometrial Cancer Consortium (E2C2). Main analyses were performed among postmenopausal women: 6,335 endometrial cancer cases and 18,453 controls. Using individual data, study-specific odd ratios (ORs) and their corresponding 95% confidence intervals (CIs) were estimated with logistic regression and pooled analyses were conducted using random-effects meta-analyses. A non-significant inverse association was observed between endometrial cancer and night shift work (OR=0.89, 95%CI=0.72-1.09; I2=0.0%, Pheterogeneity=0.676). Associations did not vary by shift type (permanent or rotating), or duration of night work. Categorizations of short (<7h) or long (≥9h) sleep duration were not associated with endometrial cancer risk (ORshort=1.02, 95%CI=0.95-1.10; I2=55.3%, Pheterogeneity=0.022; ORlong=0.93, 95%CI=0.81-1.06; I2=11.5%, Pheterogeneity=0.339). No associations were observed per 1-h increment of sleep (OR=0.98, 95%CI=0.95-1.01; I2=46.1%, Pheterogeneity=0.063), but an inverse association was identified among obese women (OR=0.93, 95%CI=0.89-0.98 per 1-h increment; I2=12.7%, Pheterogeneity=0.329). Overall, these pooled analyses provide evidence that night shift work and sleep duration are not strong risk factors for endometrial cancer in postmenopausal women.
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Neoplasias Endometriales , Horario de Trabajo por Turnos , Femenino , Humanos , Neoplasias Endometriales/epidemiología , Neoplasias Endometriales/etiología , Factores de Riesgo , Horario de Trabajo por Turnos/efectos adversos , Sueño , Duración del Sueño , Tolerancia al Trabajo ProgramadoRESUMEN
Deep learning (DL) can accelerate the prediction of prognostic biomarkers from routine pathology slides in colorectal cancer (CRC). However, current approaches rely on convolutional neural networks (CNNs) and have mostly been validated on small patient cohorts. Here, we develop a new transformer-based pipeline for end-to-end biomarker prediction from pathology slides by combining a pre-trained transformer encoder with a transformer network for patch aggregation. Our transformer-based approach substantially improves the performance, generalizability, data efficiency, and interpretability as compared with current state-of-the-art algorithms. After training and evaluating on a large multicenter cohort of over 13,000 patients from 16 colorectal cancer cohorts, we achieve a sensitivity of 0.99 with a negative predictive value of over 0.99 for prediction of microsatellite instability (MSI) on surgical resection specimens. We demonstrate that resection specimen-only training reaches clinical-grade performance on endoscopic biopsy tissue, solving a long-standing diagnostic problem.
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Algoritmos , Neoplasias Colorrectales , Humanos , Biomarcadores , Biopsia , Inestabilidad de Microsatélites , Neoplasias Colorrectales/genéticaRESUMEN
Autopsy rates are declining, while major discrepancies between autopsies and clinical diagnoses remain. Still, little is known about the impact of suspected underlying diseases, for example, a diagnosis of cancer, on the autopsy rate. The aim of this study was to investigate the relation between the clinical cause of death, a history of cancer, and the medical autopsy rate using data from the Netherlands Cohort Study on Diet and Cancer (NLCS), a large prospective cohort study with a long follow-up. The NLCS is a prospective study initiated in 1986 and includes 120,852 persons (58,279 males and 62,573 females), 55-69 years of age at the time of enrollment. The NLCS was linked with the Dutch Nationwide Pathology Databank (PALGA), the Dutch Population Register (GBA), the Netherlands Cancer Registry, and the causes of death registry (Statistics Netherlands). If applicable, the 95% confidence intervals were calculated. During the follow-up of the NLCS, 59,760 deaths were recorded by linkage with the GBA from 1991 until 2009. Of these, a medical autopsy was performed on 3736 deceased according to linkage with PALGA, resulting in an overall autopsy rate of 6.3%. Major variations in the autopsy rate were observed according to the cause of death. The autopsy rate increased according to the number of contributing causes of death. Lastly, a diagnosis of cancer affected the autopsy rate. The clinical cause of death and a history of cancer both influenced the medical autopsy rate in a large national cohort. The insight this study provides may help clinicians and pathologists counteracting the further downfall of the medical autopsy.
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Neoplasias , Masculino , Femenino , Humanos , Anciano , Autopsia , Estudios Prospectivos , Estudios de Cohortes , Causas de Muerte , Estudios RetrospectivosRESUMEN
The association between combined healthy lifestyle and postmenopausal breast cancer risk has been studied in various cohort studies, but only few evaluated the association with estrogen/progesterone (ER/PR) receptor subtypes of breast cancer, with inconsistent results. The relationship of a healthy lifestyle score (HLS) with risk of postmenopausal breast cancer (subtypes) was investigated in the Netherlands Cohort Study. In 1986, 62,573 women aged 55-69 years provided information on dietary and lifestyle habits. The HLS was derived from information on smoking, body mass index, physical activity, Mediterranean diet adherence, and alcohol intake. After 20.3 years of follow-up, multivariable case-cohort analyses were based on 2321 incident breast cancer cases, and 1665 subcohort members with complete data on lifestyles and confounders. The HLS showed a statistically significant inverse relationship with postmenopausal breast cancer risk, in a linear fashion. A one-point increment of the HLS was accompanied by a Hazard Ratio (HR) reduction of 20% for overall breast cancer. The associations between HLS and risk of ER/PR breast cancer subtypes were also significantly inverse, except for ER- breast cancer where the inverse association did not reach statistical significance. Per HLS-increment of one point, the HR reduction ranged from 14% for ER-breast cancer to 29% for ER + PR- breast cancer. These findings suggest that adhering to a combination of healthy modifiable lifestyle factors may substantially reduce the risk of overall postmenopausal breast cancer and its hormone receptor subtypes.
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Neoplasias de la Mama , Dieta Mediterránea , Femenino , Humanos , Neoplasias de la Mama/epidemiología , Neoplasias de la Mama/prevención & control , Estudios de Cohortes , Países Bajos/epidemiología , Posmenopausia , Receptores de Estrógenos , Receptores de Progesterona , Estilo de Vida Saludable , Factores de RiesgoRESUMEN
Colorectal cancer (CRC) remains one of the most prevalent and deadly cancers worldwide. The tumour-node-metastasis stage (TNM) is currently the most clinically important tool to predict prognosis for CRC patients. However, patients with the same TNM stage can have different prognoses. The metabolic status of tumour cells (Warburg-subtype) has been proposed as potential prognostic factor in CRC. However, potential biological mechanisms underlying the relationship between Warburg-subtype and prognosis have not been investigated in detail. One potential mechanism could be that the metabolic status of tumour cells affects the tumour microenvironment (TME). Our objective was to investigate the relationship between Warburg-subtypes and the TME. Haematoxylin/Eosin stained tumour tissue microarray cores from 2171 CRC patients from the Netherlands Cohort Study were semi quantitatively assessed for tumour infiltrating lymphocytes (TILs) and relative tumour stroma content. 5745 cores were assessed by putting each core in one of four categories for both TILs and stroma. The relationship between Warburg-subtype, TILs, and tumour stroma content was investigated. The frequency of CRC in the different TIL categories was (n, %): very low (2538, 44.2), low (2463, 42.9), high (722, 12.6), and very high (22, 0.4). The frequency of CRC in the different tumour stroma content categories was: ≤ 25% (2755, 47.9), > 25% ≤ 50% (1553, 27) > 50% ≤ 75% (905, 15.8), and > 75% (532, 9.3). There was neither an association between Warburg-subtype and tumour stroma content (p = 0.229) nor between Warburg-subtype and TILs (p = 0.429). This is the first study to investigate the relationship between Warburg-subtypes and the TME in a large population-based series of CRC patients. Our data suggest that the prognostic value of Warburg-subtypes cannot be directly attributed to differences in TILs or tumour stroma content. Our results require confirmation in an independent series.
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Neoplasias Colorrectales , Microambiente Tumoral , Humanos , Estudios de Cohortes , Pronóstico , Linfocitos Infiltrantes de Tumor/patología , Neoplasias Colorrectales/patologíaRESUMEN
Cancer of Unknown Primary (CUP) is metastatic cancer with an unidentifiable primary tumour origin during life. It remains difficult to study the occurrence and aetiology of CUP. Hitherto, it is unclear whether risk factors are associated with CUP, yet identifying these factors could reveal whether CUP is a specific entity or a cluster of metastasised cancers from various primary tumour origins. Epidemiological studies on possible CUP risk factors were systematically searched in PubMed and Web of Science on February 1st, 2022. Studies, published before 2022, were included if they were observational human-based, provided relative risk estimates, and investigated possible CUP risk factors. A total of 5 case-control and 14 cohort studies were included. There appears to be an increased risk for smoking in relation to CUP. However, limited suggestive evidence was found to link alcohol consumption, diabetes mellitus, and family history of cancer as increased risks for CUP. No conclusive associations could be made for anthropometry, food intake (animal or plant-based), immunity disorders, lifestyle (overall), physical activity, or socioeconomic status and CUP risk. No other CUP risk factors have been studied. This review highlights smoking, alcohol consumption, diabetes mellitus and family history of cancer as CUP risk factors. Yet, there remains insufficient epidemiological evidence to conclude that CUP has its own specific risk factor profile.
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Diabetes Mellitus , Neoplasias Primarias Desconocidas , Humanos , Neoplasias Primarias Desconocidas/patología , Factores de Riesgo , Fumar , Consumo de Bebidas AlcohólicasRESUMEN
BACKGROUND: Limited data from prospective studies suggest that higher dietary intake of long-chain omega-3 polyunsaturated fatty acids (LCn3PUFA), which hold anti-inflammatory properties, may reduce endometrial cancer risk; particularly among certain subgroups characterized by body mass and tumor pathology. MATERIALS AND METHODS: Data from 12 prospective cohort studies participating in the Epidemiology of Endometrial Cancer Consortium were harmonized as nested case-control studies, including 7268 endometrial cancer cases and 26,133 controls. Habitual diet was assessed by food frequency questionnaire, from which fatty acid intakes were estimated. Two-stage individual-participant data mixed effects meta-analysis estimated adjusted odds ratios (OR) and 95% confidence intervals (CI) through logistic regression for associations between study-specific energy-adjusted quartiles of LCn3PUFA and endometrial cancer risk. RESULTS: Women with the highest versus lowest estimated dietary intakes of docosahexaenoic acid, the most abundant LCn3PUFA in diet, had a 9% increased endometrial cancer risk (Quartile 4 vs. Quartile 1: OR 1.09, 95% CI: 1.01-1.19; P trend = 0.04). Similar elevated risks were observed for the summary measure of total LCn3PUFA (OR 1.07, 95% CI: 0.99-1.16; P trend = 0.06). Stratified by body mass index, higher intakes of LCn3PUFA were associated with 12-19% increased endometrial cancer risk among overweight/obese women and no increased risk among normal-weight women. Higher associations appeared restricted to White women. The results did not differ by cancer grade. CONCLUSION: Higher dietary intakes of LCn3PUFA are unlikely to reduce endometrial cancer incidence; rather, they may be associated with small to moderate increases in risk in some subgroups of women, particularly overweight/obese women.
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Neoplasias Endometriales , Ácidos Grasos Omega-3 , Humanos , Femenino , Estudios Prospectivos , Sobrepeso , Dieta , Obesidad/epidemiología , Obesidad/complicaciones , Neoplasias Endometriales/epidemiología , Neoplasias Endometriales/prevención & control , Neoplasias Endometriales/etiología , Modelos Logísticos , Factores de RiesgoRESUMEN
PURPOSE: Tumor location and tumor node metastasis (TNM) stage guide treatment decisions in colorectal cancer (CRC) patients. However, patients with the same disease stage do not benefit equally from adjuvant therapy. Hence, there remains an urgent clinical need to identify prognostic and/or predictive biomarker(s) to personalize treatment decisions. In this exploratory study, we investigated whether our previously defined metabolic Warburg-subtypes can predict which CRC patients might derive survival benefit from adjuvant therapy. METHODS: Information regarding treatment (surgery only: n = 1451; adjuvant radiotherapy: n = 82; or adjuvant chemotherapy: n = 260) and Warburg-subtype (Warburg-low: n = 485, -moderate: n = 641, or -high: n = 667) was available for 1793 CRC patients from the Netherlands Cohort Study (NLCS). Kaplan-Meier curves and Cox regression models were used to investigate survival benefit from adjuvant therapy compared to surgery-only for the different Warburg-subtypes. RESULTS: Patients with Warburg-moderate CRC (HRCRC-specific 0.64; 95% CI 0.47-0.86, HRoverall 0.61; 95% CI 0.47-0.80), and possibly Warburg-high CRC (HRCRC-specific 0.86; 95% CI 0.65-1.14, HRoverall 0.82; 95% CI 0.64-1.05), had survival benefit from adjuvant therapy. No survival benefit was observed for patients with Warburg-low CRC (HRCRC-specific 1.07; 95% CI 0.76-1.52, HRoverall 0.95; 95% CI 0.70-1.30). There was a significant interaction between Warburg-subtype and adjuvant therapy for CRC-specific survival (p = 0.049) and overall survival (p = 0.035). CONCLUSION: Our results suggest that Warburg-subtypes may predict survival benefit from adjuvant therapy in CRC patients. A survival benefit from adjuvant therapy was observed for patients with Warburg-moderate and possibly Warburg-high CRC, but not for patients with Warburg-low CRC. Future prospective studies are necessary to validate our findings.
Asunto(s)
Neoplasias Colorrectales , Humanos , Estudios de Cohortes , Estudios Prospectivos , Quimioterapia Adyuvante , Pronóstico , Neoplasias Colorrectales/tratamiento farmacológico , Estadificación de NeoplasiasRESUMEN
Knowledge on the role of diet in tinnitus onset is mostly based on few cross-sectional studies. In 2016-2019 we conducted a hospital-based case-control study in northern Italy on 185 incident idiopathic tinnitus cases and 198 controls, providing data on dietary habits through a 37-item food-frequency questionnaire. Odds ratios (OR) for tinnitus risk were derived through unconditional multiple logistic regression models. Moderate-to-high vs. low intake of caffeine (OR, 0.49; 95% confidence interval (CI), 0.24-0.99) and butter (OR, 0.46; 95% CI, 0.23-0.93), and high vs. low intake of poultry (OR, 0.43; 95% CI, 0.23-0.81), prosciutto (OR, 0.44; 95% CI, 0.23-0.85), and legumes (OR, 0.50; 95% CI, 0.28-0.92) were inversely associated with tinnitus onset. Other food items, including cereals, red meat, fish, vegetables, and fruit did not show any statistically significant relationship. The variety of food consumed decreased the risk of tinnitus (OR for at least 20 vs. less than 16 different food items, 0.47; 95% CI, 0.24-0.90). Our findings highlight the importance of diet in tinnitus onset and confirm a potential inverse association of protein-rich food and caffeine on the incidence of tinnitus. Confirmation of our findings in longitudinal studies is necessary before proving any diet recommendations for tinnitus prevention.
Asunto(s)
Acúfeno , Animales , Factores de Riesgo , Acúfeno/epidemiología , Acúfeno/etiología , Estudios de Casos y Controles , Estudios Transversales , Cafeína , Dieta/efectos adversos , Verduras , Frutas , Conducta Alimentaria , Italia/epidemiologíaRESUMEN
BACKGROUND: Diet, alcohol, cigarette smoking, physical inactivity, and body mass index have been studied as risk factors for renal cell cancer (RCC). The joint effects of these lifestyle factors, captured as Healthy Lifestyle Index (HLI), were examined in one previous study. This study aims to investigate the association between HLI score and RCC risk in the prospective Netherlands Cohort Study (NLCS). METHODS: A case-cohort analysis (3,767 subcohort members, 485 cases) was conducted using NLCS data (n = 120,852). Data on aforementioned risk factors was used to calculate HLI score, ranging 0-20, with higher scores reflecting healthier lifestyles. RCC occurrence was obtained by record linkage to cancer registries. Multivariable-adjusted proportional hazard models were used to calculate Hazard Ratios (HR) and 95% Confidence Intervals (95%CI). RESULTS: Compared to participants in the unhealthiest HLI category, participants within the healthiest category had a lower RCC risk (HR = 0.79, 95%CI = 0.56-1.10, p for trend 0.045). A standard deviation (± 3-unit) increase in HLI score was not statistically significantly associated with a lower RCC risk (HR = 0.92, 95%CI = 0.83-1.01). This association was stronger after excluding diet or alcohol from the score, although confidence intervals overlap. CONCLUSIONS: Adherence to a healthy lifestyle was weakly, though not statistically significantly, associated with a lower RCC risk.