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BACKGROUND: There is insufficient evidence to provide recommendations for leisure-time physical activity among workers across various occupational physical activity levels. This study aimed to assess the association of leisure-time physical activity with cardiovascular and all-cause mortality across occupational physical activity levels. METHODS: This study utilized individual participant data from 21 cohort studies, comprising both published and unpublished data. Eligibility criteria included individual-level data on leisure-time and occupational physical activity (categorized as sedentary, low, moderate, and high) along with data on all-cause and/or cardiovascular mortality. A 2-stage individual participant data meta-analysis was conducted, with separate analysis of each study using Cox proportional hazards models (Stage 1). These results were combined using random-effects models (Stage 2). RESULTS: Higher leisure-time physical activity levels were associated with lower all-cause and cardiovascular mortality risk across most occupational physical activity levels, for both males and females. Among males with sedentary work, high compared to sedentary leisure-time physical activity was associated with lower all-cause (hazard ratios (HR) = 0.77, 95% Confidence interval(95%CI): 0.70-0.85) and cardiovascular mortality (HR = 0.76, 95%CI: 0.66-0.87) risk. Among males with high levels of occupational physical activity, high compared to sedentary leisure-time physical activity was associated with lower all-cause (HR = 0.84, 95%CI: 0.74-0.97) and cardiovascular mortality (HR = 0.79, 95%CI: 0.60-1.04) risk, while HRs for low and moderate levels of leisure-time physical activity ranged between 0.87 and 0.97 and were not statistically significant. Among females, most effects were similar but more imprecise, especially in the higher occupational physical activity levels. CONCLUSION: Higher levels of leisure-time physical activity were generally associated with lower mortality risks. However, results for workers with moderate and high occupational physical activity levels, especially women, were more imprecise. Our findings suggests that workers may benefit from engaging in high levels of leisure-time physical activity, irrespective of their level of occupational physical activity.

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OBJECTIVE: Health effects of different physical activity domains (ie, during leisure time, work and transport) are generally considered positive. Using Active Worker consortium data, we assessed independent associations of occupational and leisure-time physical activity (OPA and LTPA) with all-cause mortality. DESIGN: Two-stage individual participant data meta-analysis. DATA SOURCE: Published and unpublished cohort study data. ELIGIBILITY CRITERIA: Working participants aged 18-65 years. METHODS: After data harmonisation, we assessed associations of OPA and LTPA with all-cause mortality. In stage 1, we analysed data from each study separately using Cox survival regression, and in stage 2, we pooled individual study findings with random-effects modelling. RESULTS: In 22 studies with up to 590 497 participants from 11 countries, during a mean follow-up of 23.1 (SD: 6.8) years, 99 743 (16%) participants died. Adjusted for LTPA, body mass index, age, smoking and education level, summary (ie, stage 2) hazard ration (HRs) and 95% confidence interval (95% CI) for low, moderate and high OPA among men (n=2 96 134) were 1.01 (0.99 to 1.03), 1.05 (1.01 to 1.10) and 1.12 (1.03 to 1.23), respectively. For women (n=2 94 364), HRs (95% CI) were 0.98 (0.92 to 1.04), 0.96 (0.92 to 1.00) and 0.97 (0.86 to 1.10), respectively. In contrast, higher levels of LTPA were inversely associated with mortality for both genders. For example, for women HR for low, moderate and high compared with sedentary LTPA were 0.85 (0.81 to 0.89), 0.78 (0.74 to 0.81) and 0.75 (0.65 to 0.88), respectively. Effects were attenuated when adjusting for income (although data on income were available from only 9 and 6 studies, for men and women, respectively). CONCLUSION: Our findings indicate that OPA may not result in the same beneficial health effects as LTPA.

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Carcinogenesis is closely related to the expression, maintenance, and stability of DNA. These processes are regulated by one-carbon metabolism (1CM), which involves several vitamins of the complex B (folate, B2, B6, and B12), whereas alcohol disrupts the cycle due to the inhibition of folate activity. The relationship between nutrients related to 1CM (all aforementioned vitamins and alcohol) in breast cancer has been reviewed. The interplay of genes related to 1CM was also analyzed. Single nucleotide polymorphisms located in those genes were selected by considering the minor allele frequency in the Caucasian population and the linkage disequilibrium. These genes were used to perform several in silico functional analyses (considering corrected p-values < 0.05 as statistically significant) using various tools (FUMA, ShinyGO, and REVIGO) and databases such as the Kyoto Encyclopedia of Genes and Genomes (KEGG) and GeneOntology (GO). The results of this study showed that intake of 1CM-related B-complex vitamins is key to preventing breast cancer development and survival. Also, the genes involved in 1CM are overexpressed in mammary breast tissue and participate in a wide variety of biological phenomena related to cancer. Moreover, these genes are involved in alterations that give rise to several types of neoplasms, including breast cancer. Thus, this study supports the role of one-carbon metabolism B-complex vitamins and genes in breast cancer; the interaction between both should be addressed in future studies.

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BACKGROUND: Adiposity has been characterized as a modifiable risk factor for prostate cancer. Its association with outcomes after prostate cancer diagnosis, however, must be better understood, and more evidence is needed to facilitate the development of lifestyle guidance for patients with prostate cancer. METHODS: We investigated the associations between adiposity indices close to prostate cancer diagnosis (up to 2 years before or up to 5 years after diagnosis) and mortality in 1968 men of the European Prospective Investigation into Cancer and Nutrition cohort. Men were followed up for a median of 9.5 years. Cox proportional hazards models were adjusted for age and year of diagnosis, disease stage and grade, and smoking history and stratified by country. RESULTS: Each 5-unit increment in prediagnosis or postdiagnosis body mass index combined was associated with a 30% higher rate of all-cause mortality and a 49% higher rate of prostate cancer-specific mortality. Similarly, each 5-unit increment in prediagnosis body mass index was associated with a 35% higher rate of all-cause mortality and a 51% higher rate of prostate cancer-specific mortality. The associations were less strong for postdiagnosis body mass index, with a lower number of men in analyses. Less clear positive associations were shown for waist circumference, hip circumference, and waist to hip ratio, but data were limited. CONCLUSIONS: Elevated levels of adiposity close to prostate cancer diagnosis could lead to higher risk of mortality; therefore, men are encouraged to maintain a healthy weight. Additional research is needed to confirm whether excessive adiposity after prostate cancer diagnosis could worsen prognosis.

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The healthy lifestyle index (HLI), defined as the unweighted sum of individual lifestyle components, was used to investigate the combined role of lifestyle factors on health-related outcomes. We introduced weighted outcome-specific versions of the HLI, where individual lifestyle components were weighted according to their associations with disease outcomes. Within the European Prospective Investigation into Cancer and Nutrition (EPIC), we examined the association between the standard and the outcome-specific HLIs and the risk of T2D, CVD, cancer, and all-cause premature mortality. Estimates of the hazard ratios (HRs), the Harrell's C-index and the population attributable fractions (PAFs) were compared. For T2D, the HR for 1-SD increase of the standard and T2D-specific HLI were 0.66 (95% CI: 0.64, 0.67) and 0.43 (0.42, 0.44), respectively, and the C-index were 0.63 (0.62, 0.64) and 0.72 (0.72, 0.73). Similar, yet less pronounced differences in HR and C-index were observed for standard and outcome-specific estimates for cancer, CVD and all-cause mortality. PAF estimates for mortality before age 80 were 57% (55%, 58%) and 33% (32%, 34%) for standard and mortality-specific HLI, respectively. The use of outcome-specific HLI could improve the assessment of the role of lifestyle factors on disease outcomes, thus enhancing the definition of public health recommendations.

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ABSTRACT Purpose: To evaluate the effectiveness of mapping-targeted biopsies (MTB) on the index lesion for the detection of clinically significant prostate cancer (csPCa) in transperineal fusion-image prostate biopsies. Materials and Methods: A retrospective analysis was conducted on 309 men with suspected PCa who underwent prostate biopsies at the Creu Blanca reference center in Barcelona, Spain. The Prostate Imaging-Reporting and Data System (PI-RADS v.2.1) of the magnetic resonance images (MRI) were reclassified by an expert radiologist reading of pre-biopsy biparametric MRI used for segmentation of suspected lesions. Transperineal MTB of suspicious lesions and 12-core systematic biopsies were performed using the Artemis™ platform. CsPCa was defined as International Society of Urological Pathology grade group ≥ 2. Results: CsPCa was detected in 192 men (62.1%), with detection rates of 6.3% for PI-RADS 2, 26.8% for PI-RADS 3, 87.3% for PI-RADS 4, and 93.1% for PI-RADS 5. MTB of the index lesion identified 185 csPCa (96.3%). CsPCa was detected solely in systematic biopsies in three cases (1.6%), while an additional four cases (2.1%) were identified only in the second suspected lesion. A predictive model for csPCa detection in MTB of the index lesion was developed, with an AUC of 0.918 (95% CI 0.887-0.950). Conclusions: This model had the potential to avoid 23.3% of prostate biopsies without missing additional csPCa cases. MTB of the index lesion was highly effective for identifying csPCa in fusion transperineal prostate biopsies. A developed predictive model successfully reduced the need for almost one quarter of biopsies without missing csPCa cases.

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Recurrence after colorectal cancer resection is rarely documented in the general population while a key clinical determinant for patient survival. We identified 8785 patients with colorectal cancer diagnosed between 2010 and 2013 and clinically followed up to 2020 in 15 cancer registries from seven European countries (Bulgaria, Switzerland, Germany, Estonia, France, Italy, and Spain). We estimated world age-standardized net survival using a flexible cumulative excess hazard model. Recurrence rates were calculated for patients with initially resected stage I, II, or III cancer in six countries, using the actuarial survival method. The proportion of nonmetastatic resected colorectal cancers varied from 58.6% to 78.5% according to countries. The overall 5-year net survival by country ranged between 60.8% and 74.5%. The absolute difference between the 5-year survival extremes was 12.8 points for stage II (Bulgaria vs Switzerland), 19.7 points for stage III (Bulgaria vs. Switzerland) and 14.8 points for Stage IV and unresected cases (Bulgaria vs. Switzerland or France). Five-year cumulative rate of recurrence among resected patients with stage I-III was 17.7%. As compared to the mean of the whole cohort, the risk of developing a recurrence did not differ between countries except a lower risk in Italy for both stage I/II and stage III cancers and a higher risk in Spain for stage III. Survival after colorectal cancer differed across the concerned European countries while there were slight differences in recurrence rates. Population-based collection of cancer recurrence information is crucial to enhance efforts for evidence-based management of colorectal cancer follow up.

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BACKGROUND: The consumption of processed meats (PMs) and red meats are linked to the likelihood of developing colorectal cancer. Various theories have been proposed to explain this connection, focusing on nitrosyl-heme and heme iron intake. We hypothesized that differences in nitrosyl-heme and heme iron intakes will be associated with various sociodemographic and lifestyle factors. METHODS: The study included 38,471 healthy volunteers (62% females) from five Spanish regions within the EPIC-Spain cohort. High-Performance Liquid Chromatography (HPLC) determined nitrosyl-heme and heme iron levels in the 39 most consumed PMs. Food intake was assessed using validated questionnaires in interviews. Nitrosyl-heme and heme iron intakes, adjusted for sex, age, body mass index (BMI), center, and energy intake, were expressed as geometric means due to their skewed distribution. Variance analysis identified foods explaining the variability of nitrosyl-heme and heme iron intakes. RESULTS: The estimated intakes were 528.6 µg/day for nitrosyl-heme and 1676.2 µg/day for heme iron. Significant differences in nitrosyl-heme intake were found by sex, center, energy, and education level. Heme iron intake varied significantly by sex, center, energy, and smoking status. "Jamón serrano" and "jamón cocido/jamón de York" had the highest intake values, while "morcilla asturiana" and "sangrecilla" were key sources of nitrosyl-heme and heme iron. CONCLUSIONS: This is the first study to estimate levels of nitrosyl-heme intake directly in PMs for a large sample, revealing variations based on sex, BMI, smoking, and activity. Its data aids future exposure estimations in diverse populations.

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PURPOSE: To evaluate the effectiveness of mapping-targeted biopsies (MTB) on the index lesion for the detection of clinically significant prostate cancer (csPCa) in transperineal fusion-image prostate biopsies. MATERIALS AND METHODS: A retrospective analysis was conducted on 309 men with suspected PCa who underwent prostate biopsies at the Creu Blanca reference center in Barcelona, Spain. The Prostate Imaging-Reporting and Data System (PI-RADS v.2.1) of the magnetic resonance images (MRI) were reclassified by an expert radiologist reading of pre-biopsy biparametric MRI used for segmentation of suspected lesions. Transperineal MTB of suspicious lesions and 12-core systematic biopsies were performed using the Artemis™ platform. CsPCa was defined as International Society of Urological Pathology grade group ≥ 2. RESULTS: CsPCa was detected in 192 men (62.1%), with detection rates of 6.3% for PI-RADS 2, 26.8% for PI-RADS 3, 87.3% for PI-RADS 4, and 93.1% for PI-RADS 5. MTB of the index lesion identified 185 csPCa (96.3%). CsPCa was detected solely in systematic biopsies in three cases (1.6%), while an additional four cases (2.1%) were identified only in the second suspected lesion. A predictive model for csPCa detection in MTB of the index lesion was developed, with an AUC of 0.918 (95% CI 0.887-0.950). CONCLUSIONS: This model had the potential to avoid 23.3% of prostate biopsies without missing additional csPCa cases. MTB of the index lesion was highly effective for identifying csPCa in fusion transperineal prostate biopsies. A developed predictive model successfully reduced the need for almost one quarter of biopsies without missing csPCa cases.

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Thyroid cancer (TC) is substantially more common in women than in men, pointing to a possible role of sex steroid hormones. We investigated the association between circulating sex steroid hormones, sex hormone binding globulin (SHBG) and the risk of differentiated TC in men and women within the European Prospective Investigation into Cancer and nutrition (EPIC) cohort. During follow-up, we identified 333 first primary incident cases of differentiated TC (152 in pre/peri-menopausal women, 111 in post-menopausal women, and 70 in men) and 706 cancer-free controls. Women taking exogenous hormones at blood donation were excluded. Plasma concentrations of testosterone, androstenedione, dehydroepiandrosterone, estradiol, estrone and progesterone (in pre-menopausal women only) were performed using liquid chromatography/mass spectrometry method. SHBG concentrations were measured by immunoassay. Odds ratios (ORs) were estimated using conditional logistic regression models adjusted for possible confounders. No significant associations were observed in men and postmenopausal women, while a borderline significant increase in differentiated TC risk was observed with increasing testosterone (adjusted OR T3 vs T1: 1.68, 95% CI: 0.96-2.92, ptrend = .06) and androstenedione concentrations in pre/perimenopausal women (adjusted OR T3 vs T1: 1.78, 95% CI: 0.96-3.30, ptrend = .06, respectively). A borderline decrease in risk was observed for the highest progesterone/estradiol ratio (adjusted OR T3 vs T1: 0.54, 95% CI: 0.28-1.05, ptrend = .07). Overall, our results do not support a major role of circulating sex steroids in the etiology of differentiated TC in post-menopausal women and men but may suggest an involvement of altered sex steroid production in pre-menopausal women.

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Environmental factors play a role in breast cancer development. While metals and metalloids (MMs) include some carcinogens, their association with breast cancer depends on the element studied. Most studies focus on individual MMs, but the combined effects of metal mixtures remain unclear. The aim of this study was to analyze the relationship between the joint exposure to MMs and the risk of developing female breast cancer. We conducted a case-control study within the multicenter prospective EPIC-Spain cohort. Study population comprised 292 incident cases and 286 controls. Plasma concentrations of 16 MMs were quantified at recruitment. Potential confounders were collected using a questionnaire and anthropometric measurements. Mixed-effects logistic regression models were built to explore the effect of individual MMs. Quantile-based g computation models were applied to identify the main mixture components and to estimate the joint effect of the metal mixture. The geometric means were highest for Cu (845.6 ng/ml) and Zn (604.8 ng/ml). Cases had significantly higher Cu concentrations (p = 0.010) and significantly lower Zn concentrations (p < 0.001). Cu (+0.42) and Mn (+0.13) showed the highest positive weights, whereas Zn (-0.61) and W (-0.16) showed the highest negative weights. The joint effect of the metal mixture was estimated at an OR = 4.51 (95%CI = 2.32-8.79), suggesting a dose-response relationship. No evidence of non-linearity or non-additivity was found. An unfavorable exposure profile, primarily characterized by high Cu and low Zn levels, could lead to a significant increase in the risk of developing female breast cancer. Further studies are warranted to confirm these findings.

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Dioxins and polychlorinated biphenyls (PCBs) are toxic, endocrine disruptors and persistent chemicals for which the main exposure source is diet due to their bioaccumulation and biomagnification in food chains. Cohort studies in the general populations have reported inconsistent associations between these chemicals in serum/plasma and mortality. Our objective was to study the association between dietary intake of 17 dioxins and 35 PCBs and all-cause, cancer-specific and cardiovascular-specific mortalities were assessed in the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort. Dietary intake of dioxins and PCBs was assessed combining EPIC food consumption data with European food contamination data provided by the European Food Safety Authority. We applied multivariable Cox regressions. The analysis included 451,390 adults (mean ± SD age:51.1 ± 9.7 years) with 46,627 deaths and a median follow-up of 17.4 years (IQR = 15.2-19.1). A U-shaped non-linear association with all-cause mortality for dietary intake of dioxins (Pnon-linearity<0.0001), DL-PCB (Pnon-linearity = 0.0001), and NDL-PCBs (Pnon-linearity<0.01) was observed. For example, the hazard ratios (95%Confidance interval) for all-cause mortality obtained with the spline model was equal to 1.03 (1.02-1.05) for low levels of intake to dioxins (7 pg TEQ/day), 0.93 (0.90-0.96) for moderate levels of intake (25 pg TEQ/day), while for high levels of intake (55 pg TEQ/day) it was 1.03 (0.97-1.09). Intake of dioxins, DL-PCBs and NDL-PCBs was not associated with cardiovascular mortality. There was no association between intakes of dioxins and cancer mortality, but a U-shaped association was observed for intake of DL-PCBs and intakes of NDL-PCBs and cancer mortality. The PCBs and dioxins are known to have endocrine disrupting properties which can lead to non-monotonic dose responses. These results need to be interpreted with caution and further studies are needed to better clarify the association between dietary intake of dioxins and PCB and mortality in the general population.

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OBJECTIVE: To explore the association between three previously identified and validated dietary patterns (Western, Prudent and Mediterranean) and breast cancer risk by tumour subtype and menopausal status. METHODS: Data from the Spanish cohort of the European Prospective Investigation into Cancer and Nutrition study provided epidemiological information (including diet and cancer incidence) from 24,892 women (639 breast cancer cases) recruited between 1992 and 1996. The associations between adherence to the three dietary patterns and breast cancer risk (overall and by tumour subtype) were explored by fitting multivariate Cox proportional hazards regression models stratified by region, among other variables. A possible interaction with menopausal status (changing over time) was explored. RESULTS: No clear association of the Prudent and Mediterranean dietary patterns with breast cancer risk was found. When compared with women with a level of adherence to the Western diet in the first quartile, women with a level of adherence in the third (hazard ratio (95 % confidence interval) (HR(95%CI)):1.37 (1.07;1.77)) and fourth quartiles (1.37 (1.03;1.83)); p for curvature of splines = 0.016) showed a non-linear increased risk, especially postmenopausal women (HR (95 % CI) 1.30 (0.98;1.72) in the third and 1.42 (1.04;1.94) in the fourth quartiles; p for curvature of splines = 0.081) and for estrogen or progesterone receptor positive with human epidermal growth factor receptor 2 negative tumours (HR (95 % CI) 1.62 (1.10;2.38) and 1.71 (1.11;2.63) for the third and fourth quartiles respectively; p for curvature of splines = 0.013). CONCLUSIONS: Intake of foods such as high-fat dairy products, red and processed meats, refined grains, sweets, caloric drinks, convenience food and sauces might be associated with a higher risk of breast cancer.

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The etiology of prostate cancer is not fully elucidated. Among environmental risk factors, endocrine-disrupting chemicals (EDCs) deserve special mention, as they alter metabolic pathways involved in hormone-dependent cancers. Epidemiological evidence assessing the carcinogenicity of EDCs is scarce. The aim of this study was to analyze the relationship between exposure to parabens and benzophenones and prostate cancer risk. We conducted a case-cohort study nested within the EPIC-Spain prospective multi-center cohort. Study population comprised 1,838 sub-cohort participants and 467 non-sub-cohort prostate cancer cases. Serum concentrations of four parabens and two benzophenones were assessed at recruitment. Covariates included age, physical activity, tobacco smoking, alcohol consumption, body mass index, educational level and diabetes. Borgan II weighted Cox proportional hazard models stratified by study center were applied. Median follow-up time was 18.6 years (range = 1.0-21.7 years). Most sub-cohort participants reached primary education at most (65.5%), were overweight (57.7%) and had a low level of physical activity (51.3%). Detection percentages varied widely, being lowest for butyl-paraben (11.3%) and highest for methyl-paraben (80.7%), which also showed the highest geometric mean (0.95 ng/ml). Cases showed significantly higher concentrations of methyl-paraben (p = 0.041) and propyl-paraben (p < 0.001). In the multivariable analysis, methyl-paraben - log-transformed (HR = 1.07; 95%CI = 1.01-1.12) and categorized into tertiles (HR = 1.60 for T3; 95%CI = 1.16-2.20) -, butyl-paraben - linear (HR = 1.19; 95%CI = 1.14-1.23) and log-transformed (HR = 1.17; 95%CI = 1.01-1.35) - and total parabens - log-transformed (HR = 1.09; 95%CI = 1.02-1.17) and categorized into tertiles (HR = 1.62 for T3; 95%CI = 1.10-2.40) - were associated with an increased prostate cancer risk. In this study, higher concentrations of methyl-, butyl-, and total parabens were positively associated with prostate cancer risk. Further research is warranted to confirm these findings.

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BACKGROUND: Stroke is a highly prevalent disease that can provoke severe disability. We evaluate a predictive model based on the Minimum Basic Data Set (MBDS) compiled by the Spain Health Ministry, obtained for the period 2008-2012 for patients with ischaemic stroke in Spain, to establish the model's validity and to optimise its calibration. The MBDS is the main clinical-administrative database for hospitalisations recorded in Spain, and to our knowledge, no predictive models for stroke mortality have previously been developed using this resource. The main study aim is to perform an external validation and recalibration of the coefficients of this predictive model with respect to a chronologically later cohort. MATERIAL AND METHODS: External validation (testing the model on a different cohort to assess its performance) and recalibration (validation with optimisation of model coefficients) were performed using the MBDS for patients admitted for ischaemic stroke in the period 2016-2018. A cohort study was designed, in which a recalibrated model was obtained by applying the variables of the original model without their coefficients. The variables from the original model were then applied to the subsequent cohort, together with the coefficients from the initial model. The areas under the curve (AUC) of the recalibration and the external validation procedure were compared. RESULTS: The recalibrated model produced an AUC of 0.743 and was composed of the following variables: age (odds ratio, OR:1.073), female sex (OR:1.143), ischaemic heart disease (OR:1.192), hypertension (OR:0.719), atrial fibrillation (OR:1.414), hyperlipidaemia (OR:0.652), heart failure (OR:2.133) and posterior circulation stroke (OR: 0.755). External validation produced an AUC of 0.726. CONCLUSIONS: The recalibrated clinical model thus obtained presented moderate-high discriminant ability and was generalisable to predict death for patients with ischaemic stroke. Rigorous external validation slightly decreased the AUC but confirmed the validity of the baseline model for the chronologically later cohort.

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Introduction: HPV infection is a common risk factor for all anogenital cancers. However, there are important differences in the epidemiology of anogenital cancers and these have not been compared considering diverse epidemiological indicators over a long period of time. To fill this gap, we investigated incidence, mortality, and survival trends of anogenital cancers over a period of three decades. Methods: We conducted an observational registry-based study using data from the population-based cancer registry of Granada in southern Spain. We collected data on all incident cases of anogenital cancer (cervical, anal, penile, vulvar, and vaginal cancer) diagnosed between 1985 and 2017. We calculated crude and age-standardized incidence and mortality rates, and 1, 3, and 5-year overall and net survival. We further conducted time-trend analysis calculating annual percent changes (APC) for each cancer site. Results: The incidence of anogenital cancers decreased slightly during the past 30 years, with the exception of vulvar cancer, where a slight increase was observed. Mortality decreased significantly for cervical cancer over the study period but increased non-significantly for the remaining cancer sites. Survival rates were similar to those reported in comparable countries and increased for cervical and vulvar cancer. Discussion: Cervical cancer was the greatest contributor to the burden of anogenital cancers and showed a marked improvement in all indicators in comparison to the remaining cancer sites.

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BACKGROUND: Metals have been postulated as environmental concerns in the etiology of Parkinson's disease (PD), but metal levels are typically measured after diagnosis, which might be subject to reverse causality. OBJECTIVE: The aim of this study was to investigate the association between prediagnostic blood metal levels and PD risk. METHODS: A case-control study was nested in a prospective European cohort, using erythrocyte samples collected before PD diagnosis. RESULTS: Most assessed metals were not associated with PD risk. Cadmium has a suggestive negative association with PD (odds ratio [95% confidence interval] for the highest quartile, 0.70 [0.42-1.17]), which diminished among never smokers. Among current smokers only, lead was associated with decreased PD risk (0.06 [0.01-0.35]), whereas arsenic showed associations toward an increased PD risk (1.85 [0.45-7.93]). CONCLUSIONS: We observe no strong evidence to support a role of metals in the development of PD. In particular, smoking may confound the association with tobacco-derived metals. © 2023 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

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Background Observational studies have shown that women with an early menopause are at higher risk of stroke compared with women with a later menopause. However, associations with stroke subtypes are inconsistent, and the causality is unclear. Methods and Results We analyzed data of the UK Biobank and EPIC-CVD (European Prospective Investigation Into Cancer and Nutrition-Cardiovascular Diseases) study. A total of 204 244 postmenopausal women without a history of stroke at baseline were included (7883 from EPIC-CVD [5292 from the subcohort], 196 361 from the UK Biobank). Pooled mean baseline age was 58.9 years (SD, 5.8), and pooled mean age at menopause was 47.8 years (SD, 6.2). Over a median follow-up of 12.6 years (interquartile range, 11.8-13.3), 6770 women experienced a stroke (5155 ischemic strokes, 1615 hemorrhagic strokes, 976 intracerebral hemorrhages, and 639 subarachnoid hemorrhages). In multivariable adjusted observational Cox regression analyses, the pooled hazard ratios per 5 years younger age at menopause were 1.09 (95% CI, 1.07-1.12) for stroke, 1.09 (95% CI, 1.06-1.13) for ischemic stroke, 1.10 (95% CI, 1.04-1.16) for hemorrhagic stroke, 1.14 (95% CI, 1.08-1.20) for intracerebral hemorrhage, and 1.00 (95% CI, 0.84-1.20) for subarachnoid hemorrhage. When using 2-sample Mendelian randomization analysis, we found no statistically significant association between genetically proxied age at menopause and risk of any type of stroke. Conclusions In our study, earlier age at menopause was related to a higher risk of stroke. We found no statistically significant association between genetically proxied age at menopause and risk of stroke, suggesting no causal relationship.

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Introduction: Previous studies measuring intervals on the oral cancer care pathway have been heterogenous, showing mixed results with regard to patient outcomes. The aims of this research were (1) to calculate pooled meta-analytic estimates for the duration of the patient, diagnostic and treatment intervals in oral cancer, considering the income level of the country, and (2) to review the evidence on the relationship of these three intervals with tumor stage at diagnosis and survival. Materials and methods: We conducted a systematic review with meta-analysis following PRISMA 2020 guidelines (pre-registered protocol CRD42020200752). Following the Aarhus statement, studies were eligible if they reported data on the length of the patient (first symptom to first presentation to a healthcare professional), diagnostic (first presentation to diagnosis), or treatment (diagnosis to start of treatment) intervals in adult patients diagnosed with primary oral cancer. The risk of bias was assessed with the Aarhus checklist. Results: Twenty-eight studies reporting on 30,845 patients met the inclusion criteria. The pooled median duration of the patient interval was 47 days (95% CI = 31-73), k = 18, of the diagnosis interval 35 days (95% CI = 21-38), k = 11, and of the treatment interval 30 days (95% CI = 23-53), k = 19. In lower-income countries, the patient and treatment intervals were significantly longer, and longer patient intervals were related to later stage at diagnosis. In studies with a lower risk of bias from high-income countries, longer treatment intervals were associated with lower survival rates. Conclusion: Interval duration on the oral cancer care pathway is influenced by the socio-economic context and may have implications for patient outcomes.

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BACKGROUND: Lung cancer is the main cause of cancer mortality worldwide and in Spain. Several previous studies have documented socio-economic inequalities in lung cancer mortality but these have focused on specific provinces or cities. The goal of this study was to describe lung cancer mortality in Spain by sex as a function of socio-economic deprivation. METHODS: We analysed all registered deaths from lung cancer during the period 2011-2017 in Spain. Mortality data was obtained from the National Institute of Statistics, and socio-economic level was measured with the small-area deprivation index developed by the Spanish Society of Epidemiology, with the census tract of residence at the time of death as the unit of analysis. We computed crude and age-standardized rates per 100,000 inhabitants by sex, deprivation quintile, and type of municipality (rural, semi-rural, urban) considering the 2013 European standard population (ASR-E). We further calculated ASR-E ratios between the most deprived (Q5) and the least deprived (Q1) areas and mapped census tract smoothed standardized lung cancer mortality ratios by sex. RESULTS: We observed 148,425 lung cancer deaths (80.7% in men), with 73.5 deaths per 100,000 men and 17.1 deaths per 100,000 women. Deaths from lung cancer in men were five times more frequent than in women (ASR-E ratio = 5.3). Women residing in the least deprived areas had higher mortality from lung cancer (ASR-E = 22.2), compared to women residing in the most deprived areas (ASR-E = 13.2), with a clear gradient among the quintiles of deprivation. For men, this pattern was reversed, with the highest mortality occurring in areas of lower socio-economic level (ASR-E = 99.0 in Q5 vs. ASR-E = 86.6 in Q1). These socio-economic inequalities remained fairly stable over time and across urban and rural areas. CONCLUSIONS: Socio-economic status is strongly related to lung cancer mortality, showing opposite patterns in men and women, such that mortality is highest in women residing in the least deprived areas and men residing in the most deprived areas. Systematic surveillance of lung cancer mortality by socio-economic status may facilitate the assessment of public health interventions aimed at mitigating cancer inequalities in Spain.

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