Smoking and risk for amyotrophic lateral sclerosis: analysis of the EPIC cohort.

OBJECTIVE: Cigarette smoking has been reported as "probable" risk factor for Amyotrophic Lateral Sclerosis (ALS), a poorly understood disease in terms of aetiology. The extensive longitudinal data of the European Prospective Investigation into Cancer and Nutrition (EPIC) were used to evaluate age-specific mortality rates from ALS and the role of cigarette smoking on the risk of dying from ALS. METHODS: A total of 517,890 healthy subjects were included, resulting in 4,591,325 person-years. ALS cases were ascertained through death certificates. Cox hazard models were built to investigate the role of smoking on the risk of ALS, using packs/years and smoking duration to study dose-response. RESULTS: A total of 118 subjects died from ALS, resulting in a crude mortality rate of 2.69 per 100,000/year. Current smokers at recruitment had an almost two-fold increased risk of dying from ALS compared to never smokers (HR = 1.89, 95% C.I. 1.14-3.14), while former smokers at the time of enrollment had a 50% increased risk (HR = 1.48, 95% C.I. 0.94-2.32). The number of years spent smoking increased the risk of ALS (p for trend = 0.002). Those who smoked more than 33 years had more than a two-fold increased risk of ALS compared with never smokers (HR = 2.16, 95% C.I. 1.33-3.53). Conversely, the number of years since quitting smoking was associated with a decreased risk of ALS compared with continuing smoking. INTERPRETATION: These results strongly support the hypothesis of a role of cigarette smoking in aetiology of ALS. We hypothesize that this could occur through lipid peroxidation via formaldehyde exposure

Smoking and Risk for Amyotrophic Lateral Sclerosis: Analysis of the EPIC Cohort

Objective: Cigarette smoking has been reported as “probable” risk factor for Amyotrophic Lateral Sclerosis (ALS), a poorly understood disease in terms of aetiology. The extensive longitudinal data of the European Prospective Investigation into Cancer and Nutrition (EPIC) were used to evaluate age-specific mortality rates from ALS and the role of cigarette smoking on the risk of dying from ALS. Methods: A total of 517,890 healthy subjects were included, resulting in 4,591,325 person-years. ALS cases were ascertained through death certificates. Cox hazard models were built to investigate the role of smoking on the risk of ALS, using packs/years and smoking duration to study dose-response. Results: A total of 118 subjects died from ALS, resulting in a crude mortality rate of 2.69 per 100,000/year. Current smokers at recruitment had an almost two-fold increased risk of dying from ALS compared to never smokers (HR = 1.89, 95% C.I. 1.14-3.14), while former smokers at the time of enrolment had a 50% increased risk (HR = 1.48, 95% C.I. 0.94-2-32). The number of years spent smoking increased the risk of ALS (p for trend = 0.002). Those who smoked more than 33 years had more than a two-fold increased risk of ALS compared with never smokers (HR = 2.16, 95% C.I. 1.33-3.53). Conversely, the number of years since quitting smoking was associated with a decreased risk of ALS compared with continuing smoking. Interpretation: These results strongly support the hypothesis of a role of cigarette smoking in aetiology of ALS. We hypothesize that this could occur through lipid peroxidation via formaldehyde exposure. Ann Neurol 2009;65:378-38

Social Inequalities and Mortality in Europe - Results from a Large Multi-National Cohort

Background: Socio-economic inequalities in mortality are observed at the country level in both North America and Europe. The purpose of this work is to investigate the contribution of specific risk factors to social inequalities in cause-specific mortality using a large multi-country cohort of Europeans. Methods: A total of 3,456,689 person/years follow-up of the European Prospective Investigation into Cancer and Nutrition (EPIC) was analysed. Educational level of subjects coming from 9 European countries was recorded as proxy for socioeconomic status (SES). Cox proportional hazard model's with a step-wise inclusion of explanatory variables were used to explore the association between SES and mortality; a Relative Index of Inequality (RII) was calculated as measure of relative inequality. Results: Total mortality among men with the highest education level is reduced by 43% compared to men with the lowest (HR 0.57, 95% C.I. 0.52-0.61); among women by 29% (HR 0.71, 95% C.I. 0.64-0.78). The risk reduction was attenuated by 7% in men and 3% in women by the introduction of smoking and to a lesser extent (2% in men and 3% in women) by introducing body mass index and additional explanatory variables (alcohol consumption, leisure physical activity, fruit and vegetable intake) (3% in men and 5% in women). Social inequalities were highly statistically significant for all causes of death examined in men. In women, social inequalities were less strong, but statistically significant for all causes of death except for cancer-related mortality and injuries. Discussion: In this European study, substantial social inequalities in mortality among European men and women which cannot be fully explained away by accounting for known common risk factors for chronic diseases are reporte

Social Inequalities and Mortality in Europe - Results from a Large Multi-National Cohort

Background: Socio-economic inequalities in mortality are observed at the country level in both North America and Europe. The purpose of this work is to investigate the contribution of specific risk factors to social inequalities in cause-specific mortality using a large multi-country cohort of Europeans. Methods: A total of 3,456,689 person/years follow-up of the European Prospective Investigation into Cancer and Nutrition (EPIC) was analysed. Educational level of subjects coming from 9 European countries was recorded as proxy for socioeconomic status (SES). Cox proportional hazard model’s with a step-wise inclusion of explanatory variables were used to explore the association between SES and mortality; a Relative Index of Inequality (RII) was calculated as measure of relative inequality. Results: Total mortality among men with the highest education level is reduced by 43% compared to men with the lowest (HR 0.57, 95% C.I. 0.52-0.61); among women by 29% (HR 0.71, 95% C.I. 0.64-0.78). The risk reduction was attenuated by 7% in men and 3% in women by the introduction of smoking and to a lesser extent (2% in men and 3% in women) by introducing body mass index and additional explanatory variables (alcohol consumption, leisure physical activity, fruit and vegetable intake) (3% in men and 5% in women). Social inequalities were highly statistically significant for all causes of death examined in men. In women, social inequalities were less strong, but statistically significant for all causes of death except for cancer-related mortality and injuries. Discussion: In this European study, substantial social inequalities in mortality among European men and women which cannot be fully explained away by accounting for known common risk factors for chronic diseases are reported

Prediagnostic body fat and risk of death from amyotrophic lateral sclerosis The EPIC cohort

<p>Objectives: The aim of this study was to investigate for the first time the association between body fat and risk of amyotrophic lateral sclerosis (ALS) with an appropriate prospective study design.</p><p>Methods: The EPIC (European Prospective Investigation into Cancer and Nutrition) study included 518,108 individuals recruited from the general population across 10 Western European countries. At recruitment, information on lifestyle was collected and anthropometric characteristics were measured. Cox hazard models were fitted to investigate the associations between anthropometric measures and ALS mortality.</p><p>Results: Two hundred twenty-two ALS deaths (79 men and 143 women) occurred during the follow-up period (mean follow-up = 13 years). There was a statistically significant interaction between categories of body mass index and sex regarding ALS risk (p = 0.009): in men, a significant linear decrease of risk per unit of body mass index was observed (hazard ratio = 0.93, 95% confidence interval 0.86-0.99 per kg/m(2)); among women, the risk was more than 3-fold increased for underweight compared with normal-weight women. Among women, a significant risk reduction increasing the waist/hip ratio was also evident: women in the top quartile had less than half the risk of ALS compared with those in the bottom quartile (hazard ratio = 0.48, 95% confidence interval 0.25-0.93) with a borderline significant p value for trend across quartiles (p = 0.056).</p><p>Conclusion: Increased prediagnostic body fat is associated with a decreased risk of ALS mortality. Neurology (R) 2013; 80: 829-838</p>

Hazard ratio (HRs) for mortality across the Relative Index of Inequality (RII) in men (blue diamonds) and women (red squares), in Northern (Norway, Sweden, Denmark), Central (UK, Netherlands, and Germany), and Southern (Spain, Italy, and Greece) European countries; fully adjusted model (including smoking status at recruitment, BMI in 2.5 kg/m² categories, alcohol consumption at recruitment, leisure physical activity, and fruit and vegetables consumption, and stratifyied by age and centre of recruitment).

<p>Hazard ratio (HRs) for mortality across the Relative Index of Inequality (RII) in men (blue diamonds) and women (red squares), in Northern (Norway, Sweden, Denmark), Central (UK, Netherlands, and Germany), and Southern (Spain, Italy, and Greece) European countries; fully adjusted model (including smoking status at recruitment, BMI in 2.5 kg/m² categories, alcohol consumption at recruitment, leisure physical activity, and fruit and vegetables consumption, and stratifyied by age and centre of recruitment).</p

Demographic characteristics of the sample, and smoking status, alcohol consumption, physical activity, and BMI at recruitment in men.

<p>IQR =  inter quartile range.</p

Demographic characteristics of the sample, and smoking status, alcohol consumption, physical activity, and BMI at recruitment in women.

<p>IQR =  inter quartile range.</p

Cumulative mortality at different ages by education level and sex (blue lines for men, orange/red lines for women; circles for none-primary education, triangles for technical education, squares for secondary education, diamonds for university degree).

<p>Cumulative mortality at different ages by education level and sex (blue lines for men, orange/red lines for women; circles for none-primary education, triangles for technical education, squares for secondary education, diamonds for university degree).</p

Relative Index of Inequality (RII) for specific causes of death in men and women.

*<p>stratified by centre of recruitment and age; †including smoking status at recruitment (never smoker, former smoker ≥10 years, former smoker <10 years, former smoker unknown, current smoker <15 cigarettes/day, 15–24 cigarettes/day, ≥25 cigarettes/day) and stratified by centre of recruitment; ‡ including smoking status at recruitment (as in †) and BMI in 2.5 kg/m² categories (<20.0; 20.1–22.5; 22.6–25.0; 25.1–22.5; 22.6–30.0; 30.1–32.5; 32.6–35.0; 35.1–37.5; ≥37.6) and stratified by centre of recruitment; ** including smoking status at recruitment and BMI (as in ‡) and alcohol consumption at recruitment (g/day, in deciles of distribution), leisure physical activity (inactive, moderately active, active, and unknown), and fruit and vegetables consumption; ††models including smoking are adjusted for smoking status at recruitment as a categorical variable (never, current, or former smoker); age at the start of, and duration of, smoking (in years) as continuous variables; a linear and a quadratic term for current quantity smoked (number of cigarettes per day); and two interaction terms between duration and quantity and between age at start and duration; ‡‡ never smoker only.</p