Kaaks Rudolf, Sookthai Disorn, Łuczyńska Anna, Oakes Christopher C, Becker Susen, Johnson Theron, Johansson Annsofie, Melin Beatrice, Sjöberg Klas, Trichopoulos Dimitrios, Trichopoulou Antonia, Lagiou Pagona, Mattiello Amalia, Tumino Rosario, Masala Giovanna, Agnoli Claudia, Boeing Heiner, Aleksandrova Krasimira, Brennan Paul, Franceschi Silvia, Roulland Sandrine, Casabonne Delphine, de Sanjose Silvia, Sánchez María-José, Huerta José María, Ardanaz Eva, Sala Nuria, Overvad Kim, Tjønneland Anne, Halkjær Jytte, Weiderpass Elisabete, Bueno-de-Mesquita H B As, Vermeulen Roel, Peeters Petra H, Vineis Paolo, Kelly Rachel S, Khaw Kay-Tee, Travis Ruth C, Key Timothy J, Riboli Elio, Nieters Alexandra
Division of Cancer Epidemiology, German Cancer Research Center Heidelberg, Heidelberg, Germany.
Center for Chronic Immunodeficiency, University Medical Center Freiburg, Freiburg, Germany.
Cancer Epidemiol Biomarkers Prev. 2015 Mar;24(3):538-45. doi: 10.1158/1055-9965.EPI-14-1107. Epub 2014 Dec 26.
Chronic lymphocytic leukemia (CLL) is a chronic disease that often progresses slowly from a precursor stage, monoclonal B-cell lymphocytosis (MBL), and that can remain undiagnosed for a long time.
Within the European Prospective Investigation into Cancer cohort, we measured prediagnostic plasma sCD23 for 179 individuals who eventually were diagnosed with CLL and an equal number of matched control subjects who remained free of cancer.
In a very large proportion of CLL patients' plasma sCD23 was clearly elevated 7 or more years before diagnosis. Considering sCD23 as a disease predictor, the area under the ROC curve (AUROC) was 0.95 [95% confidence interval (CI), 0.90-1.00] for CLL diagnosed within 0.1 to 2.7 years after blood measurement, 0.90 (95% CI, 0.86-0.95) for diagnosis within 2.8 to 7.3 years, and 0.76 (95% CI, 0.65-0.86) for CLL diagnosed between 7.4 and 12.5 years. Even at a 7.4-year and longer time interval, elevated plasma sCD23 could predict a later clinical diagnosis of CLL with 100% specificity at >45% sensitivity.
Our findings provide unique documentation for the very long latency times during which measurable B-cell lymphoproliferative disorder exists before the clinical manifestation of CLL.
Our findings have relevance for the interpretation of prospective epidemiologic studies on the causes of CLL in terms of reverse causation bias. The lag times indicate a time frame within which an early detection of CLL would be theoretically possible. Cancer Epidemiol Biomarkers Prev; 24(3); 538-45. ©2014 AACR.
慢性淋巴细胞白血病（CLL）是一种慢性疾病，通常从前体阶段单克隆B细胞淋巴细胞增多症（MBL）开始缓慢进展，且可能长时间未被诊断。
在欧洲癌症前瞻性调查队列中，我们测量了179名最终被诊断为CLL的个体以及数量相等的匹配对照受试者（未患癌症）的诊断前血浆可溶性CD23（sCD23）水平。
在很大比例的CLL患者中，血浆sCD23在诊断前7年或更长时间明显升高。将sCD23作为疾病预测指标，血液检测后0.1至2.7年内诊断为CLL的受试者，其ROC曲线下面积（AUROC）为0.95 [95%置信区间（CI），0.90 - 1.00]；2.8至7.3年内诊断的受试者，AUROC为0.90（95% CI，0.86 - 0.95）；7.4至12.5年内诊断为CLL的受试者，AUROC为0.76（95% CI，0.65 - 0.86）。即使在7.4年及更长时间间隔时，血浆sCD23升高仍可预测CLL的后期临床诊断，特异性为100%，敏感性>45%。
我们的研究结果为CLL临床表现出现之前可测量的B细胞淋巴增殖性疾病存在的很长潜伏期提供了独特的记录。
我们的研究结果对于解释CLL病因的前瞻性流行病学研究中的反向因果偏差具有重要意义。这些延迟时间表明了理论上早期检测CLL的时间范围。《癌症流行病学、生物标志物与预防》；24(3)；538 - 45。©2014美国癌症研究协会。
