Bracci Massimo, Manzella Nicola, Copertaro Alfredo, Staffolani Sara, Strafella Elisabetta, Barbaresi Mariella, Copertaro Benedetta, Rapisarda Venerando, Valentino Matteo, Santarelli Lory
Occupational Medicine, Department of Clinical and Molecular Sciences, Polytechnic University of Marche, Via Tronto 10/a, 60020 Torrette, Ancona, Italy.
Scand J Work Environ Health. 2014 May 1;40(3):295-304. doi: 10.5271/sjweh.3414. Epub 2014 Jan 8.
Impairment of clock gene expression and changes in melatonin and 17-β-estradiol levels may constitute biological alterations underlying the increased risk of breast cancer among shift workers. The aim of this study was to compare levels of selected core clock gene expression, 6-sulfatoxymelatonin (aMT6s), and 17-β-estradiol between rotational shift work (SW) and daytime (DT) workers after a day off.
The cross-sectional study comprised 60 nurses with ≥2 years of SW and 56 permanent DT nurses. Transcript levels of circadian genes BMAL1, CLOCK, NPAS2, CRY1, CRY2, PER1, PER2, PER3, and REVERBα were determined by quantitative real-time polymerase chain reaction (PCR) in lymphocytes. All participants were tested in the early follicular phase of the menstrual cycle. Samples were collected at the beginning of the morning-shift after a regular night's sleep on a day off. Chronotype and sociodemographic characteristics were also evaluated.
We found a significantly higher expression of BMAL1, CLOCK, NPAS2, PER1, PER2, and REVERBα and a lower expression of PER3, CRY1 and CRY2 among SW compared to DT nurses. SW participants did not demonstrate a significant difference in aMT6s levels, but they did show significantly higher 17-β-estradiol levels compared to DT nurses. Multiple linear regression analysis confirmed the role of SW on expression of BMAL1 (β 0.21, P=0.040), CLOCK (β 0.35, P=0.008), NPAS2 (β 0.30, P=0.012), PER1 (β 0.33, P=0.008), PER2 (β 0.19, P=0.047), PER3 (β -0.27, P=0.012), CRY1 (β -0.33, P=0.002), CRY2 (β -0.31, P=0.005), REVERBα (β 0.19, P=0.045), and on 17-β-estradiol levels (β 0.32, P=0.003). The analysis also confirmed the role of chronotype as an independent factor for PER1 (β 0.48, P=0.001) and PER2 (β -0.22, P=0.022) expression, and 17-β-estradiol levels (β 0.26, P=0.011).
Rotating SW nurses show alterations in peripheral clock gene expression and 17-β-estradiol levels at the beginning of the morning shift after a day off.
生物钟基因表达受损以及褪黑素和17-β-雌二醇水平的变化可能构成轮班工作者患乳腺癌风险增加的潜在生物学改变。本研究的目的是比较轮班工作(SW)护士和日班(DT)护士在休息一天后的选定核心生物钟基因表达水平、6-硫酸氧褪黑素(aMT6s)和17-β-雌二醇水平。
这项横断面研究包括60名从事轮班工作≥2年的护士和56名长期从事日班工作的护士。通过定量实时聚合酶链反应(PCR)测定淋巴细胞中昼夜节律基因BMAL1、CLOCK、NPAS2、CRY1、CRY2、PER1、PER2、PER3和REVERBα的转录水平。所有参与者均在月经周期的卵泡早期进行检测。在休息一天后正常夜间睡眠后的早班开始时采集样本。还评估了昼夜节律类型和社会人口学特征。
我们发现,与日班护士相比,轮班工作护士中BMAL1、CLOCK、NPAS2、PER1、PER2和REVERBα的表达显著更高,而PER3、CRY1和CRY2的表达更低。轮班工作参与者的aMT6s水平没有显著差异,但与日班护士相比,他们的17-β-雌二醇水平显著更高。多元线性回归分析证实了轮班工作对BMAL1(β 0.21,P = 0.040)、CLOCK(β 0.35,P = 0.008)、NPAS2(β 0.30,P = 0.012)、PER1(β 0.33,P = 0.008)、PER2(β 0.19,P = 0.047)、PER3(β -0.27,P = 0.012)、CRY1(β -0.33,P = 0.002)、CRY2(β -0.31,P = 0.005)、REVERBα(β 0.19,P = 0.045)表达以及17-β-雌二醇水平(β 0.32,P = 0.003)的作用。分析还证实了昼夜节律类型作为PER1(β 0.48,P = 0.001)和PER2(β -0.22,P = 0.022)表达以及17-β-雌二醇水平(β 0.26,P = 0.011)的独立影响因素的作用。
轮班工作护士在休息一天后的早班开始时,外周生物钟基因表达和17-β-雌二醇水平出现改变。