Division of Cancer Epidemiology and Genetics, National Cancer Institute, 6120 Executive Boulevard, EPS 5024, MSC 7234, Bethesda, MD 20852-7234, USA.
Cancer Epidemiol Biomarkers Prev. 2010 Apr;19(4):932-7. doi: 10.1158/1055-9965.EPI-10-0004. Epub 2010 Mar 23.
Epidemiologic data on serum melatonin, a marker of circadian rhythms, and cancer are sparse due largely to the lack of reliable assays with high sensitivity to detect relatively low melatonin levels in serum collected during daylight, as commonly available in most epidemiologic studies.
To help expand epidemiologic research on melatonin, we assessed the reproducibility and refined a currently available melatonin RIA, and evaluated its application to epidemiologic investigations by characterizing melatonin levels in serum, urine, and/or plasma in 135 men from several ethnic groups.
Reproducibility was high for the standard 1.0-mL serum [mean coefficient of variation (CV), 6.9%; intraclass correlation coefficient (ICC), 97.4%; n = 2 serum pools in triplicate] and urine-based (mean CV, 3.5%; ICC, 99.9%) assays. Reproducibility for the 0.5-mL refined-serum assay was equally good (mean CV, 6.6%; ICC, 99.0%). There was a positive correlation between morning serum melatonin and 6-sulfatoxymelatonin in 24-hour urine (r = 0.46; P = 0.008; n = 49 subjects). Melatonin levels in serum-plasma pairs had a high correlation (r = 0.97; P < 1x10(-4); n = 20 pairs). Morning serum melatonin levels were five times higher than those from the afternoon (before 9 a.m. mean, 11.0 pg/mL, versus after 11 a.m. mean, 2.0 pg/mL). Chinese men had lower melatonin levels (mean, 3.4 pg/mL), whereas Caucasian, African-American, and Ghanaian men had similar levels (mean, 6.7-8.6 pg/mL).
These results suggest that melatonin can be detected reliably in serum samples collected in epidemiologic studies in various racial groups.
With improved assays, it may be possible to investigate the role of melatonin and the emerging circadian rhythm hypothesis in cancer etiology in epidemiologic studies.
由于缺乏高灵敏度的可靠检测方法来检测白天采集的血清中相对较低的褪黑素水平,因此关于血清褪黑素(昼夜节律的标志物)与癌症的流行病学数据非常有限,而这种方法在大多数流行病学研究中都很常见。
为了帮助扩大褪黑素的流行病学研究,我们评估了现有的褪黑素 RIA 的重现性,并对其进行了改进,通过对来自不同种族的 135 名男性的血清、尿液和/或血浆中的褪黑素水平进行特征描述,评估了该方法在流行病学研究中的应用。
1.0ml 血清标准检测[2 个血清池重复 3 次的平均变异系数(CV)为 6.9%,组内相关系数(ICC)为 97.4%]和尿液检测[平均 CV 为 3.5%,ICC 为 99.9%]的重现性均较高。0.5ml 改良血清检测的重现性同样良好(平均 CV 为 6.6%,ICC 为 99.0%)。24 小时尿液中晨时血清褪黑素与 6-硫酸褪黑素之间呈正相关(r = 0.46,P = 0.008,n = 49 例)。血清-血浆对中褪黑素水平的相关性很高(r = 0.97,P < 1x10(-4),n = 20 对)。晨时血清褪黑素水平是下午(上午 9 点前均值为 11.0pg/ml,上午 11 点后均值为 2.0pg/ml)的五倍。中国人的褪黑素水平较低(均值为 3.4pg/ml),而白种人、非裔美国人和加纳人的褪黑素水平相似(均值为 6.7-8.6pg/ml)。
这些结果表明,在不同种族的流行病学研究中,可以可靠地检测血清样本中的褪黑素。
随着检测方法的改进,有可能在流行病学研究中调查褪黑素和新兴的昼夜节律假说在癌症病因学中的作用。