Analysis of amyotrophic lateral sclerosis as a multistep process: a population-based modelling study.
Analysis of amyotrophic lateral sclerosis as a multistep process: a population-based modelling study.
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DOI：
10.1016/s1474-4422(14)70219-4
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发表时间：
2014-11
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影响因子：
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通讯作者：
Pearce N
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作者：
Al-Chalabi A;Calvo A;Chio A;Colville S;Ellis CM;Hardiman O;Heverin M;Howard RS;Huisman MHB;Keren N;Leigh PN;Mazzini L;Mora G;Orrell RW;Rooney J;Scott KM;Scotton WJ;Seelen M;Shaw CE;Sidle KS;Swingler R;Tsuda M;Veldink JH;Visser AE;van den Berg LH;Pearce N
肌萎缩侧索硬化症与某些癌症有共同的特征，例如在晚年发病更常见，进展通常迅速，疾病影响特定的细胞类型，并显示复杂的遗传。我们使用一个最初应用于癌症流行病学的模型来研究肌萎缩侧索硬化是一个多步骤过程的假设。我们从爱尔兰（登记日期1995 - 2012年）、荷兰（2006 - 12年）、意大利（1995 - 2004年）、苏格兰（1989 - 98年）和英格兰（2002 - 09年）肌萎缩侧索硬化症人群登记中按年龄和性别生成发病率数据，并计算每个登记的年龄和性别调整发病率。我们用最小二乘回归法对年龄特异性发病率的对数与年龄的对数进行了回归。我们在每个寄存器内进行了分析，并且还进行了组合分析，针对寄存器进行了调整。我们从约3400万人的集水区人口中确定了6274例肌萎缩侧索硬化症。我们注意到，在所有5个登记中心，对数发病率和对数年龄之间存在线性关系：英格兰r2 = 0·95，爱尔兰r2 = 0·99，意大利r2 = 0·95，荷兰r2 = 0·99，苏格兰r2 = 0·97;总体r2 = 0·99。所有5个寄存器给出的线性斜率估计值相似，范围为4.5至5.1，置信区间重叠。所有五个登记册的组合得出的总体斜率为4.8（95% CI 4.5 - 5.0），男性（4.6，4.3 - 4.9）和女性（5.0，4.5 - 5.5）的估计值相似。肌萎缩侧索硬化症的对数发病率和对数发病年龄之间的线性关系与疾病的多阶段模型一致。斜率估计表明肌萎缩侧索硬化症是一个六步过程。确定这些步骤可导致预防和治疗途径。英国医学研究理事会;英国经济和社会研究理事会;爱尔兰卫生研究委员会;荷兰卫生研究与发展组织（ZonMw）;意大利卫生部和教育、大学和研究部;英格兰、威尔士和北爱尔兰爱尔兰运动神经元疾病协会;以及欧盟委员会（第七框架计划）。
Amyotrophic lateral sclerosis shares characteristics with some cancers, such as onset being more common in later life, progression usually being rapid, the disease affecting a particular cell type, and showing complex inheritance. We used a model originally applied to cancer epidemiology to investigate the hypothesis that amyotrophic lateral sclerosis is a multistep process. We generated incidence data by age and sex from amyotrophic lateral sclerosis population registers in Ireland (registration dates 1995–2012), the Netherlands (2006–12), Italy (1995–2004), Scotland (1989–98), and England (2002–09), and calculated age and sex-adjusted incidences for each register. We regressed the log of age-specific incidence against the log of age with least squares regression. We did the analyses within each register, and also did a combined analysis, adjusting for register. We identified 6274 cases of amyotrophic lateral sclerosis from a catchment population of about 34 million people. We noted a linear relationship between log incidence and log age in all five registers: England r2=0·95, Ireland r2=0·99, Italy r2=0·95, the Netherlands r2=0·99, and Scotland r2=0·97; overall r2=0·99. All five registers gave similar estimates of the linear slope ranging from 4·5 to 5·1, with overlapping confidence intervals. The combination of all five registers gave an overall slope of 4·8 (95% CI 4·5–5·0), with similar estimates for men (4·6, 4·3–4·9) and women (5·0, 4·5–5·5). A linear relationship between the log incidence and log age of onset of amyotrophic lateral sclerosis is consistent with a multistage model of disease. The slope estimate suggests that amyotrophic lateral sclerosis is a six-step process. Identification of these steps could lead to preventive and therapeutic avenues. UK Medical Research Council; UK Economic and Social Research Council; Ireland Health Research Board; The Netherlands Organisation for Health Research and Development (ZonMw); the Ministry of Health and Ministry of Education, University, and Research in Italy; the Motor Neurone Disease Association of England, Wales, and Northern Ireland; and the European Commission (Seventh Framework Programme).