van Poppel G, van Aspert A, Heynen T, Vooys G P, Ockhuizen T
TNO Nutrition, Zeist, The Netherlands.
Eur J Cancer Prev. 1997 Jun;6(3):294-9. doi: 10.1097/00008469-199706000-00007.
The use of biomarkers is a promising approach to the study of human cancer risk. Bronchial metaplasia in sputum cytology may be a marker for potential premalignancy that can be used for population studies. We recently performed a randomized, controlled trial in smokers on the effect of 14 weeks beta-carotene (20mg/day) on markers for DNA damage. We now have evaluated the application of sputum cytology in this study and performed a preliminary evaluation of the effect of beta-carotene. Of the 150 potential participants in this trial 75 were not eligible because they failed to produce sputum samples (n = 29), or because samples were unsatisfactory (n = 46). The eligible group was older (41 vs 37 years) and had smoked longer (23 vs 19 years), but had similar cigarette consumption (mean 21/day) and plasma cotinine levels. Metaplasia was graded in seven categories. Only 11 subjects (15%) showed minor or mild atypia on study entry. Agreement within and between observers was 95% within the same or an adjacent category. We observed no significant correlation between before and after treatment final metaplasia scores in either the beta-carotene (Spearman R = 0.18, P = 0.3) or placebo group (Spearman R = 0.17, P = 0.3). Initial metaplasia scores were somewhat higher in the beta-carotene group (n = 33) than in the placebo group (n = 42) (P = 0.06). Final metaplasia scores were similar in both groups (P = 0.69), and there was no decrease in metaplasia scores in the beta-carotene group (P = 0.75). This study indicates that sputum cytology may not yet be a readily applicable marker in studies of a healthy asymptomatic population, because many smokers do not spontaneously produce sputum, more severe lesions are rare, and variation over time in the minor lesions in large. Therefore, the preliminary evidence that beta-carotene has no influence should be interpreted with care.
生物标志物的应用是研究人类癌症风险的一种很有前景的方法。痰细胞学检查中的支气管化生可能是潜在癌前病变的一个标志物，可用于人群研究。我们最近在吸烟者中进行了一项随机对照试验，研究连续14周补充β-胡萝卜素（20毫克/天）对DNA损伤标志物的影响。我们现在评估了痰细胞学检查在本研究中的应用情况，并对β-胡萝卜素的效果进行了初步评估。在该试验的150名潜在参与者中，75人不符合条件，原因是他们未能咳出痰液样本（n = 29），或样本不合格（n = 46）。符合条件的组年龄更大（41岁对37岁），吸烟时间更长（23年对19年），但每日吸烟量（平均21支/天）和血浆可替宁水平相似。化生分为七个等级。只有11名受试者（15%）在研究开始时表现出轻度或中度异型性。同一观察者或不同观察者之间在同一或相邻等级内的一致性为95%。在β-胡萝卜素组（Spearman相关系数R = 0.18，P = 0.3）或安慰剂组（Spearman相关系数R = 0.17，P = 0.3）中，我们均未观察到治疗前后最终化生评分之间存在显著相关性。β-胡萝卜素组（n = 33）的初始化生评分略高于安慰剂组（n = 42）（P = 0.06）。两组的最终化生评分相似（P = 0.69），且β-胡萝卜素组的化生评分没有下降（P = 0.75）。这项研究表明，在健康无症状人群的研究中，痰细胞学检查可能还不是一种易于应用的标志物，因为许多吸烟者不会自发咳出痰液，更严重的病变很少见，且轻度病变随时间的变化很大。因此，关于β-胡萝卜素没有影响的初步证据应谨慎解读。
