Objective
Metals have been suggested as a risk factor for amyotrophic lateral sclerosis (ALS), but only retrospective studies are available to date. We compared metal levels in prospectively ...collected blood samples from ALS patients and controls, to explore whether metals are associated with ALS mortality.
Methods
A nested ALS case–control study was conducted within the prospective EPIC (European Prospective Investigation into Cancer and Nutrition) cohort. Cases were identified through death certificates. We analyzed metal levels in erythrocyte samples obtained at recruitment, as a biomarker for metal exposure from any source. Arsenic, cadmium, copper, lead, manganese, mercury, selenium, and zinc concentrations were measured by inductively coupled plasma–mass spectrometry. To estimate ALS risk, we applied conditional logistic regression models.
Results
The study population comprised 107 cases (65% female) and 319 controls matched for age, sex, and study center. Median time between blood collection and ALS death was 8 years (range = 1–15). Comparing the highest with the lowest tertile, cadmium (odds ratio OR = 2.04, 95% confidence interval CI = 1.08–3.87) and lead (OR = 1.89, 95% CI = 0.97–3.67) concentrations suggest associations with increased ALS risk. Zinc was associated with a decreased risk (OR = 0.50, 95% CI = 0.27–0.94). Associations for cadmium and lead remained when limiting analyses to noncurrent smokers.
Interpretation
This is the first study to compare metal levels before disease onset, minimizing reverse causation. The observed associations suggest that cadmium, lead, and zinc may play a role in ALS etiology. Cadmium and lead possibly act as intermediates on the pathway from smoking to ALS. ANN NEUROL 20209999:n/a–n/a
Objective
Breast cancer survival is lower in low‐ and middle‐income countries (LMICs) partially due to many women being diagnosed with late‐stage disease. The patient interval refers to the time ...elapsed between the detection of symptoms and the first consultation with a healthcare provider and is considered one of the core indicators for early diagnosis and treatment. The goal of the current research was to conduct a meta‐analysis of the duration of the patient interval in LMICs and investigate the socio‐demographic and socio‐cultural factors related to longer delays in presentation.
Methods
We conducted a systematic review with meta‐analysis (pre‐registered protocol CRD42020200752). We searched seven information sources (2009–2022) and included 50 articles reporting the duration of patient intervals for 18,014 breast cancer patients residing in LMICs.
Results
The longest patient intervals were reported in studies from the Middle East (3–4 months), followed by South‐East Asia (2 months), Africa (1–2 months), Latin America (1 month), and Eastern Europe (1 month). Older age, not being married, lower socio‐economic status, illiteracy, low knowledge about cancer, disregarding symptoms or not attributing them to cancer, fear, negative beliefs about cancer, and low social support were related to longer delays across most regions. Longer delays were also related to use of alternative medicine in the Middle East, South‐East Asia, and Africa and distrust in the healthcare system in Eastern Europe.
Conclusions
There is large variation in the duration of patient intervals across LMICs in different geographical regions. Patient intervals should be reduced and, for this purpose, it is important to explore their determinants taking into account the social, cultural, and economic context.
Recent epidemiological research suggests that near road traffic-related pollution may cause chronic disease, as well as exacerbation of related pathologies, implying that the entire "chronic disease ...progression" should be attributed to air pollution, no matter what the proximate cause was. We estimated the burden of childhood asthma attributable to air pollution in 10 European cities by calculating the number of cases of 1) asthma caused by near road traffic-related pollution, and 2) acute asthma events related to urban air pollution levels. We then expanded our approach to include coronary heart diseases in adults. Derivation of attributable cases required combining concentration-response function between exposures and the respective health outcome of interest (obtained from published literature), an estimate of the distribution of selected exposures in the target population, and information about the frequency of the assessed morbidities. Exposure to roads with high vehicle traffic, a proxy for near road traffic-related pollution, accounted for 14% of all asthma cases. When a causal relationship between near road traffic-related pollution and asthma is assumed, 15% of all episodes of asthma symptoms were attributable to air pollution. Without this assumption, only 2% of asthma symptoms were attributable to air pollution. Similar patterns were found for coronary heart diseases in older adults. Pollutants along busy roads are responsible for a large and preventable share of chronic disease and related acute exacerbations in European urban areas.
•The study was conducted in an area with large industry/mining activities.•Urine and hair levels of As, Cd, Hg, Mn and Pb were determined in School children.•The only significant correlation between ...urine and hair levels was found for Hg.•Cd and Hg levels were higher than in children from other European countries.•Urine Cd and Hg levels between 25% and 50% of the children might represent a health risk.
Huelva (South West Spain) and its surrounding municipalities represent one of the most polluted estuaries in the world owing to the discharge of mining and industrial related pollutants in their proximity. A biomonitoring study was conducted to assess exposure to arsenic and some trace metals (cadmium, mercury, manganese and lead) in urine and scalp hair from a representative sample of children aged 6–9years (n=261). This is the only study simultaneously analyzing those five metal elements in children urine and hair. The potential contribution of gender, water consumption, residence area and body mass index on urinary and hair metal concentrations was also studied. Urine levels of cadmium and total mercury in a proportion (25–50%) of our children population living near industrial/mining areas might have an impact on health, likely due to environmental exposure to metal pollution. The only significant correlation between urine and hair levels was found for mercury. Children living near agriculture areas showed increased levels of cadmium and manganese (in urine) and arsenic (in hair). In contrast, decreased urine Hg concentrations were observed in children living near mining areas. Girls exhibited significantly higher trace metal concentrations in hair than boys. The greatest urine arsenic concentrations were found in children drinking well/spring water. Although human hair can be a useful tool for biomonitoring temporal changes in metal concentrations, levels are not correlated with those found in urine except for total mercury, thus providing additional information.
The European Prospective Investigation into Cancer and Nutrition (EPIC) is a multicentre prospective study conducted in 23 centres in 10 European countries. Here we review the findings from EPIC on ...the relationship between diet-related exposures and incidence or mortality from the four most frequent cancers in the European population: colorectal, breast, lung, and prostate cancer. We conducted a systematic review following PRISMA guidelines and identified 110 high-quality studies based on the EPIC cohort. Fruit and vegetable consumption had a protective effect against colorectal, breast, and lung cancer, whereas only fruit had a protective effect against prostate cancer. A higher consumption of fish and lower consumption of red and processed meat were related with a lower risk of colorectal cancer; and higher consumption of fatty fish with lower risk of breast cancer. Calcium and yogurt intake were found to protect against colorectal and prostate cancer. Alcohol consumption increased the risk for colorectal and breast cancer. Finally, adherence to the Mediterranean diet emerged as a protective factor for colorectal and breast cancer. The EPIC study results are in agreement with the latest evidence from leading authorities on cancer prevention and help to inform public prevention policies and strategies.
Longer time intervals to diagnosis and treatment are associated with worse survival for various types of cancer. The patient, diagnostic, and treatment intervals are considered core indicators for ...early diagnosis and treatment. This review estimated the median duration of these intervals for various types of cancer and compared it across high- and lower-income countries.
We conducted a systematic review with meta-analysis (prospectively registered protocol CRD42020200752). Three databases (MEDLINE, Embase, and Web of Science) and information sources including grey literature (Google Scholar, OpenGrey, EThOS, ProQuest Dissertations & Theses) were searched. Eligible articles were published during 2009 to 2022 and reported the duration of the following intervals in adult patients diagnosed with primary symptomatic cancer: patient interval (from the onset of symptoms to first presentation to a healthcare professional), diagnostic interval (from first presentation to diagnosis), and treatment interval (from diagnosis to treatment start). Interval duration was recorded in days and study medians were combined in a pooled estimate with 95% confidence intervals (CIs). The methodological quality of studies was assessed using the Aarhus checklist. A total of 410 articles representing 68 countries and reporting on 5,537,594 patients were included. The majority of articles reported data from high-income countries (n = 294, 72%), with 116 (28%) reporting data from lower-income countries. Pooled meta-analytic estimates were possible for 38 types of cancer. The majority of studies were conducted on patients with breast, lung, colorectal, and head and neck cancer. In studies from high-income countries, pooled median patient intervals generally did not exceed a month for most cancers. However, in studies from lower-income countries, patient intervals were consistently 1.5 to 4 times longer for almost all cancer sites. The majority of data on the diagnostic and treatment intervals came from high-income countries. Across both high- and lower-income countries, the longest diagnostic intervals were observed for hematological (71 days 95% CI 52 to 85, e.g., myelomas (83 days 47 to 145)), genitourinary (58 days 50 to 77, e.g., prostate (85 days 57 to 112)), and digestive/gastrointestinal (57 days 45 to 67, e.g., colorectal (63 days 48 to 78)) cancers. Similarly, the longest treatment intervals were observed for genitourinary (57 days 45 to 66, e.g., prostate (75 days 61 to 87)) and gynecological (46 days 38 to 54, e.g., cervical (69 days 45 to 108) cancers. In studies from high-income countries, the implementation of cancer-directed policies was associated with shorter patient and diagnostic intervals for several cancers. This review included a large number of studies conducted worldwide but is limited by survivor bias and the inherent complexity and many possible biases in the measurement of time points and intervals in the cancer treatment pathway. In addition, the subintervals that compose the diagnostic interval (e.g., primary care interval, referral to diagnosis interval) were not considered.
These results identify the cancers where diagnosis and treatment initiation may take the longest and reveal the extent of global disparities in early diagnosis and treatment. Efforts should be made to reduce help-seeking times for cancer symptoms in lower-income countries. Estimates for the diagnostic and treatment intervals came mostly from high-income countries that have powerful health information systems in place to record such information.
Objective
To explore the association between three previously identified dietary patterns (Western, Prudent and Mediterranean) and prostate cancer (PCa) risk by tumour aggressiveness.
Subjects and ...Methods
The Spanish cohort of the European Prospective Investigation into Cancer and Nutrition study provided dietary and epidemiological information from 15 296 men recruited during the period 1992–1996. The associations between the adherence to the three dietary patterns and PCa risk (global, for Gleason grade groups 6 and >6, and for International Society of Urological Pathology ISUP grade 1 + 2 and ISUP grade 3 + 4 + 5) was explored with multivariable Cox proportional hazards regression models stratified by centre and age.
Results
While no effect on PCa risk was detected for the Prudent and Mediterranean dietary patterns, a suggestion of a detrimental effect of the Western dietary pattern was found (hazard ratio HRQ4vsQ1 1.29 95% confidence interval {CI} 0.96;1.72). This effect was only observed for Gleason grade group >6 (HRQ3vsQ1 1.61 95% CI 1.00; 2.59 and HRQ4vsQ1 1.60 95% CI 0.96; 2.67) and in particular ISUP grade 3 + 4 + 5 tumours (HRQ2vsQ1 1.97 95% CI 0.98; 3.93; HRQ3vsQ1 2.72 (95% CI 1.35; 5.51); HRQ4vsQ1 2.29 95% CI 1.07; 4.92).
Conclusions
Our results suggest that a high adherence to a healthy diet such as that represented by the Prudent and Mediterranean dietary patterns is not enough to prevent prostate cancer. Additionally, reducing adherence to a Western‐type diet seems to be necessary.
It is unclear whether diet, and in particular certain foods or nutrients, are associated with lung cancer risk. We assessed associations of 92 dietary factors with lung cancer risk in 327 790 ...participants in the European Prospective Investigation into Cancer and Nutrition (EPIC). Cox regression yielded adjusted hazard ratios (HRs) and 95% confidence intervals (CIs) per SD higher intake/day of each food/nutrient. Correction for multiple comparisons was performed using the false discovery rate and identified associations were evaluated in the Netherlands Cohort Study (NLCS). In EPIC, 2420 incident lung cancer cases were identified during a median of 15 years of follow‐up. Higher intakes of fibre (HR per 1 SD higher intake/day = 0.91, 95% CI 0.87‐0.96), fruit (HR = 0.91, 95% CI 0.86‐0.96) and vitamin C (HR = 0.91, 95% CI 0.86‐0.96) were associated with a lower risk of lung cancer, whereas offal (HR = 1.08, 95% CI 1.03‐1.14), retinol (HR = 1.06, 95% CI 1.03‐1.10) and beer/cider (HR = 1.04, 95% CI 1.02‐1.07) intakes were positively associated with lung cancer risk. Associations did not differ by sex and there was less evidence for associations among never smokers. None of the six associations with overall lung cancer risk identified in EPIC were replicated in the NLCS (2861 cases), however in analyses of histological subtypes, inverse associations of fruit and vitamin C with squamous cell carcinoma were replicated in the NLCS. Overall, there is little evidence that intakes of specific foods and nutrients play a major role in primary lung cancer risk, but fruit and vitamin C intakes seem to be inversely associated with squamous cell lung cancer.
What's new?
Lung cancer is the leading cause of cancer death worldwide, and while smoking is the most significant factor affecting lung cancer risk, other environmental and genetic factors may contribute. Here, the authors looked for an association between the foods people eat and their lung cancer risk. Using an approach they call a diet‐wide association study, modelled after genome‐wide association studies, they evaluated 92 individual food and nutrient intakes for association with lung cancer risk. No major associations were detected for lung cancer overall, but higher fruit and vitamin C intakes were associated with lower squamous cell lung cancer risk.
Polyphenols are bioactive compounds with several anticarcinogenic activities; however, human data regarding associations with thyroid cancer (TC) is still negligible. Our aim was to evaluate the ...association between intakes of total, classes and subclasses of polyphenols and risk of differentiated TC and its main subtypes, papillary and follicular, in a European population. The European Prospective Investigation into Cancer and Nutrition cohort included 476,108 men and women from 10 European countries. During a mean follow‐up of 14 years, there were 748 incident differentiated TC cases, including 601 papillary and 109 follicular tumors. Polyphenol intake was estimated at baseline using validated center/country‐specific dietary questionnaires and the Phenol‐Explorer database. In multivariable‐adjusted Cox regression models, no association between total polyphenol and the risks of overall differentiated TC (HRQ4 vs. Q1 = 0.99, 95% confidence interval CI 0.77–1.29), papillary (HRQ4 vs. Q1 = 1.06, 95% CI 0.80–1.41) or follicular TC (HRQ4 vs. Q1 = 1.10, 95% CI 0.55–2.22) were found. No associations were observed either for flavonoids, phenolic acids or the rest of classes and subclasses of polyphenols. After stratification by body mass index (BMI), an inverse association between the intake of polyphenols (p‐trend = 0.019) and phenolic acids (p‐trend = 0.007) and differentiated TC risk in subjects with BMI ≥ 25 was observed. In conclusion, our study showed no associations between dietary polyphenol intake and differentiated TC risk; although further studies are warranted to investigate the potential protective associations in overweight and obese individuals.
What's new?
Polyphenols are secondary plant metabolites with health protective properties but whether a diet rich in polyphenols protects from thyroid cancer has not been conclusively explored. In this large prospective study, no associations were observed between dietary polyphenol intake and differentiated thyroid cancer risk. The authors recommend further studies to investigate potential associations specifically in overweight and obese individuals.
The aim of this study was to analyse the scientific evidence published to date on the potential effects on neurodevelopment and behavioural disorders in children exposed to arsenic, cadmium and ...manganese and to quantify the magnitude of the effect on neurodevelopment by pooling the results of the different studies.
We conducted a systematic review of original articles from January 2000 until March 2012, that evaluate the effects on neurodevelopment and behavioural disorders due to pre or post natal exposure to arsenic, cadmium and manganese in children up to 16years of age. We also conducted a meta-analysis assessing the effects of exposure to arsenic and manganese on neurodevelopment.
Forty-one articles that evaluated the effects of metallic elements on neurodevelopment and behavioural disorders met the inclusion criteria: 18 examined arsenic, 6 cadmium and 17 manganese. Most studies evaluating exposure to arsenic (13 of 18) and manganese (14 of 17) reported a significant negative effect on neurodevelopment and behavioural disorders. Only two studies that evaluated exposure to cadmium found an association with neurodevelopmental or behavioural disorders. The results of our meta-analysis suggest that a 50% increase of arsenic levels in urine would be associated with a 0.4 decrease in the intelligence quotient (IQ) of children aged 5–15years. Moreover a 50% increase of manganese levels in hair would be associated with a decrease of 0.7 points in the IQ of children aged 6–13years.
There is evidence that relates arsenic and manganese exposure with neurodevelopmental problems in children, but there is little information on cadmium exposure. Few studies have evaluated behavioural disorders due to exposure to these compounds, and manganese is the only one for which there is more evidence of the existence of association with attention deficit disorder with hyperactivity.
•We evaluated the association between As, Cd and Mn with neurodevelopment in children.•A 50% increase in As levels is associated with a 0.4 decrease in the IQ of children.•A 50% increase in Mn levels is associated with a 0.7 decrease in the IQ of children.•There is evidence of association between Mn exposure with attention deficit disorder with hyperactivity.