The relation between amyotrophic lateral sclerosis and inorganic selenium in drinking water: a population-based case-control study

Background  

A community in northern Italy was previously reported to have an excess incidence of amyotrophic lateral sclerosis among residents exposed to high levels of inorganic selenium in their drinking water.     

Environmental exposure to trace elements and risk of cutaneous melanoma

PURPOSE: Our aim was to examine the risk of melanoma in association with exposure to trace elements of toxicological and nutritional interest. METHODS: We analyzed the concentrations of cadmium, lead, chromium, selenium, copper and zinc in toenails of 58 patients with newly diagnosed cutaneous melanoma as well as in 58 age- and sex-matched control subjects, randomly selected from the population of Modena province in northern Italy. RESULTS: Melanoma risk was substantially unrelated to toenail levels of cadmium, chromium, lead and selenium. Subjects with higher toenail copper levels showed an excess risk, both in the crude analysis and after adjusting for sun exposure and level of education, while in both analyses high iron concentrations were associated with a decreased risk of the disease. A weak direct association between zinc levels and melanoma risk also emerged in the multivariate analysis. CONCLUSIONS: Overall, these results do not suggest an involvement of heavy metals in melanoma etiology, while they do give some support to a possible role of zinc and, in particular, copper and iron exposure in influencing disease risk. However, these findings must be evaluated with caution due to the limited statistical stability of the point estimates.     

Lead exposure and amyotrophic lateral sclerosis

BACKGROUND: Previous interview-based studies have suggested that exposure to neurotoxicants including metals might be related to ALS. METHODS: We evaluated the relation of lead exposure to ALS, using both biological measures and interviews, in a case-control study conducted in New England from 1993 to 1996. Cases (N = 109) were recruited at two hospitals in Boston, MA. Population controls (N = 256) identified by random-digit dialing were frequency-matched to cases by age, sex, and region of residence within New England. RESULTS: Risk of ALS was associated with self-reported occupational exposure to lead (odds ratio [OR] = 1.9; 95% confidence interval [CI] = 1.1-3.3), with a dose response for lifetime days of lead exposure. Blood and bone lead levels were measured in most cases (N = 107) and in a subset of controls (N = 41). Risk of ALS was associated with elevations in both blood and bone lead levels. ORs were 1.9 (95% CI = 1.4-2.6) for each microg/dl increase in blood lead, 3.6 (95% CI = 0.6-20.6) for each unit increase in log-transformed patella lead, and 2.3 (95% CI = 0.4-14.5) for each unit increase in log-transformed tibia lead. CONCLUSIONS: These results are consistent with previous reports and suggest a potential role for lead exposure in the etiology of ALS.     

A mixtures approach to solvent exposures and amyotrophic lateral sclerosis: a population-based study in Denmark

European Journal of Epidemiology - Studies of occupational solvent exposures and amyotrophic lateral sclerosis (ALS) have been conflicting. We conducted a population-based case–control study...     

Maternal age, exposure to siblings, and risk of amyotrophic lateral sclerosis

Between 1987 and 2005, the authors conducted a nested case-control study based on the Swedish Multi-Generation Register to investigate whether early life exposures, namely, maternal age at delivery and exposure to siblings, are associated with an increased risk of amyotrophic lateral sclerosis (ALS). The study comprised 768 ALS cases and five controls per case matched by birth year and gender. Odds ratios and their corresponding 95% confidence intervals for ALS were estimated by conditional logistic regression modeling. Low maternal age (< or =20 years) and high maternal age (> or =41 years) were both associated with higher risk of ALS (odds ratio (OR) = 1.5, 95% confidence interval (CI): 1.1, 2.0 and OR = 1.7, 95% CI: 1.1, 2.4, respectively). The relative risk of ALS increased slightly with increasing number of younger siblings (OR = 1.1, 95% CI: 1.0, 1.1; p = 0.02). Children whose first younger sibling was born after the age of 6 years had the greatest relative risk (OR = 1.8, 95% CI: 1.2, 2.7). Exposure to older siblings was not associated with the risk of ALS. Although the strength of the observed associations was modest, these results provided further support for the theory that early life exposures might contribute to the disease pathogenesis.     

Occupational exposure to lead compounds and risk of cancer among men: a population-based case-control study

The International Agency for Research on Cancer recently classified inorganic lead as a probable carcinogen, while organic lead remained unclassifiable. Uncertainty persists because of limited epidemiologic evidence. The authors addressed the relation between occupational exposure to lead and the risk of 11 types of cancer among men in a case-control study conducted in Montreal, Quebec, Canada, in the 1980s. Incident cases (n = 3,730) and general population controls (n = 533) were interviewed to elicit information on job history and potential confounders. Expert chemists translated each job into a list of substances to which the subject had potentially been exposed. Exposure to lead was classified into three categories: organic lead (3% of subjects ever exposed), inorganic lead (17%), and lead in gasoline emissions (39%). Odds ratios and 95% confidence intervals were estimated by logistic regression using two control groups: general population controls and cancer controls. Stomach cancer was associated with organic lead when the authors used population controls (odds ratio (OR) = 3.0, 95% confidence interval (CI): 1.2, 7.3) and cancer controls (OR = 2.0, 95% CI: 1.1, 3.8) and with substantial exposure to lead in gasoline emissions when they used cancer controls (OR = 2.9, 95% CI: 1.4, 5.9). There was no association with inorganic lead and little evidence for associations with other cancer types.     

铅暴露与肌萎缩侧索硬化症关系的研究进展

铅是用途十分广泛的一种重金属, 在使用过程中会造成环境的污染及人体健康损害。我国铅中毒的机制研究已达到了分子和细胞水平, 许多铅导致的疾病已经逐渐被认知。但是目前中国尚缺乏铅导致的肌萎缩侧索硬化症患病率的流行病学数据调查, 为此, 针对近年来国内外铅暴露的流行病学证据, 对居民健康危害及铅暴露的生物标志物研究进展进行综述。     

Dietary intake of fruits and beta-carotene is negatively associated with amyotrophic lateral sclerosis risk in Koreans: A case-control study

Objectives

Amyotrophic lateral sclerosis (ALS), a rare progressive neurodegenerative disease, has been suggested to have an association with oxidative stress, and thus antioxidant dietary factors may influence pathophysiological mechanisms or the risk of ALS. The purpose of the present study was to investigate the hypothesis that intake of fruits, rich in antioxidant nutrients, is negatively associated with the risk of ALS.

Methods

Seventy-seven Koreans diagnosed with ALS according to the EI Escorial criteria-revised and the same number of age- and sex-matched healthy controls participated in this study. Dietary intake was estimated using the standardized food frequency questionnaire.

Results

Multivariate logistic regression analysis showed that fruit consumption was negatively associated with the risk of ALS, but intake of beef, fish, and fast food were positively associated with the risk of ALS. In addition, the risk of ALS was negatively associated with intake of plant calcium and beta-carotene, while positively associated with intake of total calcium and animal calcium. Intake of vegetables and other antioxidant nutrients had no effect on the risk of ALS in the present study.

Discussion

The intake of fruits and beta-carotene decreases the risk of sporadic ALS in this present study. However, large prospective and interventional studies are needed to confirm the effect of fruits and beta-carotene intake on the risk of ALS.     

Validity of hospital morbidity records for amyotrophic lateral sclerosis. A population-based study

The validity of discharge diagnosis of amyotrophic lateral sclerosis (ALS) and of the main procedures performed during hospitalization was assessed using as gold standard the data from the Piemonte and Valle d'Aosta Register for ALS (PARALS), a collaborative population-based registry aimed at determining prospectively the incidence and the factors related to ALS outcome. All patients discharged with ICD code 335.2 (primary and secondary diagnoses) in the period 1995-1996 in Piemonte, Italy, were considered. Out of the 1,049 cases identified, 433 remained after excluding patients not resident in Piemonte and repeated admissions. Of these, 258 had a correct diagnosis of ALS (168 incident and 90 prevalent cases) after a review of clinical records. The sensitivity of discharge diagnoses was 78.9%, and the positive predictive value was 38.8%. The sensitivity for main procedures (percutaneous endoscopic gastrostomy, noninvasive ventilation, and tracheostomy) ranged between 76 and 100%. ICD codes allowed to identify 22 cases that had not been ascertained with other sources. In conclusion, hospital discharge records appear to poorly reflect the incidence of ALS, and can be used only after clinical verification of the diagnosis.     

Loss of a child and the risk of amyotrophic lateral sclerosis

Between 1987 and 2005, the authors conducted a case-control study nested within the entire Swedish population to investigate whether loss of a child due to death is associated with the risk of amyotrophic lateral sclerosis (ALS). The study comprised 2,694 incident ALS cases and five controls per case individually matched by year of birth, gender, and parity. Odds ratios and their corresponding 95% confidence intervals for ALS were estimated by using conditional logistic regression models. Compared with that for parents who never lost a child, the overall odds ratio of ALS for bereaved parents was 0.7 (95% confidence interval (CI): 0.6, 0.8) and decreased to 0.4 (95% CI: 0.2, 0.8) 11-15 years after the loss. The risk reduction was also modified by parental age at the time of loss, with the lowest odds ratio of 0.4 (95% CI: 0.2, 0.9) for parents older than age 75 years. Loss of a child due to malignancy appeared to confer a lower risk of ALS (odds ratio = 0.5, 95% CI: 0.3, 0.8) than loss due to other causes. These data indicate that the risk of developing ALS decreases following the severe stress of parental bereavement. Further studies are needed to explore potential underlying mechanisms.     

Association between occupational exposure to power frequency electromagnetic fields and amyotrophic lateral sclerosis: a review

BACKGROUND: For the past two decades, there has been concern over electromagnetic exposure and human health. While most research has focused on cancer and reproductive outcomes, there is interest in the relationship between electromagnetic fields (EMF) and neurodegenerative diseases. METHODS: We review epidemiological findings and evidence regarding the association between occupational exposure to power frequency EMFs and amyotrophic lateral sclerosis (ALS). Medline was searched for citations related to occupational hazards and ALS, literature reviews and epidemiological evaluations. RESULTS: Nine out of the ten epidemiological studies that have been conducted on the risk of ALS in relation to occupational exposure to EMF show moderate to strong relative risk estimates that supported a link between them. Although data from these studies was consistent, the causal inference to a link between EMF exposure and ALS is restricted mainly due to the lack of direct information on EMF exposure and incomplete consideration of the other potential risk factors for ALS at workplaces. For instance, electric shock, in particular, is more common in electrical occupations than in any other occupations. CONCLUSIONS: This review concludes that further studies should consider investigating the separate effect of EMF exposure and electrical shocks to make more specific interpretations. On-site measurements of EMF should be conducted to include information on EMF exposure from residences as well as workplaces to improve exposure assessment.     

Population-based case-control study of amyotrophic lateral sclerosis in western Washington State. II. Diet

The association of nutrient intake with the risk of amyotrophic lateral sclerosis (ALS) was investigated in a population-based case-control study conducted in three counties of western Washington State from 1990 to 1994. Incident ALS cases (n = 161) were identified and individually matched on age and gender to population controls (n = 321). A self-administered food frequency questionnaire was used to assess nutrient intake. Conditional logistic regression analysis was used to compute odds ratios adjusted for education, smoking, and total energy intake. The authors found that dietary fat intake was associated with an increased risk of ALS (highest vs. lowest quartile, fiber-adjusted odds ratio (OR) = 2.7, 95% confidence interval (CI): 0.9, 8.0; p for trend = 0.06), while dietary fiber intake was associated with a decreased risk of ALS (highest vs. lowest quartile, fat-adjusted OR = 0.3, 95% CI: 0.1, 0.7; p for trend = 0.02). Glutamate intake was associated with an increased risk of ALS (adjusted OR for highest vs. lowest quartile = 3.2, 95% CI: 1.2, 8.0; p for trend < 0.02). Consumption of antioxidant vitamins from diet or supplement sources did not alter the risk. The positive association with glutamate intake is consistent with the etiologic theory that implicates glutamate excitotoxicity in the pathogenesis of ALS, whereas the associations with fat and fiber intake warrant further study and biologic explanation.     

First-trimester anesthesia exposure and the risk of central nervous system defects: a population-based case-control study.

OBJECTIVES. Although up to 2% of women undergo surgery during pregnancy, teratogenic effects of general anesthesia have not been adequately studied. Recently, an association between first-trimester operations and central nervous system defects has been described. This issue was explored in a population-based case-control study. METHODS. Case patients included live-born and stillborn infants with central nervous system defects born to residents of metropolitan Atlanta, Ga, between 1968 and 1980. Control patients included normal babies frequency matched to case patients by race, birth hospital, and period of birth. Conditional logistic regression analysis was used to adjust for potential confounding factors. RESULTS. Of 694 mothers of infants with central nervous system defects, 12 reported first-trimester anesthesia exposure; 34 of 2984 control mothers reported such exposure (odds ratio [OR] = 1.7, 95% confidence interval [CI] = 0.8, 3.3). A striking association was observed between reported anesthesia exposure and hydrocephalus with another major defect (OR = 9.6, 95% CI = 3.8, 24.6). The strongest association was that of anesthesia exposure with hydrocephalus and eye defects (OR = 39.6, 95% CI = 7.5, 209.2). CONCLUSIONS. An increased risk of hydrocephalus with other defects was found among offspring of mothers with reported first-trimester anesthesia. Further studies are needed to explore the possible teratogenic effects of general anesthesia.     

From gene to disease: amyotrophic lateral sclerosis

Amyotrophic lateral sclerosis is a progressive neurological disorder. It is characterised by selective motor-neuron degeneration in the cortex, brainstem, and spinal cord. Consequently, patients suffer from muscle weakness and usually die within 3-5 years after diagnosis from respiratory insufficiency. About 5-10% of the patients have a family history of ALS, the remaining are classified as sporadic ALS. There is only limited information about genetic susceptibility factors in sporadic ALS. Some patients with familial ALS have mutations in the gene encoding for copper/zinc superoxide dismutase, a protein involved in scavenging superoxide radicals. This results in a toxic gain of function. Mutations in the gene coding for alsin, ALS2, have been shown to be responsible for an autosomal recessive form of juvenile ALS.     

Association of lead exposure with survival in amyotrophic lateral sclerosis

BACKGROUND: Reasons for the variability in survival among ALS cases are unknown but may include exposure to environmental neurotoxicants. OBJECTIVES: We aimed to determine whether lead exposure, assessed by measuring blood and bone lead levels, is associated with survival in amyotrophic lateral sclerosis (ALS). METHODS: We evaluated the relationship of lead exposure to ALS survival in 110 cases from a case-control study conducted in New England in 1993-1996 that included measurements of blood and bone lead. We retrieved information on date and cause of death through 31 December 2003 from the National Death Index Plus and the Social Security Administration Death Index. We evaluated the relationship of survival to lead exposure using Cox proportional hazard analysis, with adjustment for age, sex, and smoking. RESULTS: We found mortality data for 100 of 110 cases; 93 of 100 death certificates mentioned ALS. Median survival from diagnosis to death was 28 months. Shorter survival was associated with older age at diagnosis, female sex, bulbar onset, shorter interval between symptom onset and diagnosis, and reduced lung function. Shorter survival from diagnosis to death had a weak inverse association with blood lead (hazard ratio = 0.9; 95% confidence interval, 0.8-1.0) and a stronger inverse association with patella lead (0.5; 0.2-1.0) and tibia lead (0.3; 0.1-0.7); similar results were found for survival from symptom onset to death. CONCLUSIONS: These results suggest that lead exposure is associated with longer survival in ALS cases and, if confirmed, may shed light on mechanisms involved in disease progression.     

Environmental tobacco smoke and the risk of pancreatic cancer: findings from a Canadian population-based case-control study

BACKGROUND: Despite the fact that tobacco is a well-recognized risk factor for pancreatic cancer, no study has yet reported on the association between environmental tobacco smoke (ETS) and this malignancy. We investigated the relationship between pancreatic cancer and childhood and adult exposure to ETS using a case-control study design. METHODS: Our study population consisted of 583 pancreatic cancer cases and 4,813 population-based controls that were identified within 8 Canadian provinces between 1994 and 1997. Mail-out questionnaires were used to collect risk factor information and a lifetime residential and occupational history of exposure to ETS. RESULTS: Among never smokers, those who were exposed to ETS both as a child and as an adult had an odds ratio of 1.21 (95% CI=0.60-2.44) relative to those with no exposure. For active smoking, when the referent group consisted of never smokers who had not been regularly exposed to ETS, the risk increases were more pronounced with an increased number of years of smoking, cigarette pack-years, years since quit smoking, and average number of cigarettes smoked daily. CONCLUSIONS: Overall, our results are suggestive of a weak association between pancreatic cancer and ETS. Perhaps more importantly, they suggest that ETS smoking exposures may confound the risk of pancreatic cancer associated with active smoking measures commonly used in epidemiologic studies.     

Systemic sclerosis and occupational risk factors: a case-control study

Aims: A case–control study was carried out between 1998 and 2000 to investigate the relation between systemic sclerosis and occupational exposure.

Methods: Eighty cases of systemic sclerosis admitted consecutively to the Department of Internal Medicine at the University Hospital of Tours from 1998 to 2000 were included. For each case, two age, gender, and smoking habits matched controls hospitalised during the same period in the same department were selected. A committee of experts was set up retrospectively to assess occupational exposure. Exposure to silica dust and organic solvents (such as trichlorethylene and other chlorinated solvents, and benzene and other aromatic solvents) was investigated using semiquantitative estimates of exposure. An exposure score was calculated for each subject based on probability, intensity, daily frequency, and duration of exposure for each period of employment. The final cumulative exposure score was obtained, taking into account all periods of employment.

Results: Significant associations with SS were observed for crystalline silica, trichlorethylene, chlorinated solvents, toluene, aromatic solvents, ketones, white spirit, epoxy resins, and welding fumes. Risk of SS was significantly associated with a high final cumulative exposure score of occupational exposure to crystalline silica, trichlorethylene, chlorinated solvents, welding fumes, and any types of solvents.

Conclusion: Results confirm the influence of occupational risk factors in the occurrence of SS in both men and women. The link is not only with silica but also with other compounds such as solvents.

     

Solvent exposure and malignant lymphoma: a population-based case-control study in Germany

Aims  

To analyze the relationship between exposure to chlorinated and aromatic organic solvents and malignant lymphoma in a multi-centre, population-based case-control study.