健康男性和女性中与循环肿瘤相关叶酸受体1蛋白相关的情况。
Conditions associated with circulating tumor-associated folate receptor 1 protein in healthy men and women.
作者信息
Kelemen Linda E, Brenton James D, Parkinson Christine, C Whitaker Hayley, Piskorz Anna M, Csizmadi Ilona, Robson Paula J
机构信息
Department of Population Health Research, Alberta Health Services, Calgary, Alberta, Canada; Department of Medical Genetics, University of Calgary, Calgary, Alberta, Canada.
Cancer Research United Kingdom Cambridge Institute, University of Cambridge, Li Ka Shing Centre, Cambridge, United Kingdom; Department of Oncology, University of Cambridge, Hutchison/Medical Research Council Research Centre, Cambridge, United Kingdom; National Institute for Health Research Cambridge Biomedical Research Centre, Cambridge, United Kingdom; Cambridge Experimental Cancer Medicine Centre, Cambridge, United Kingdom.
出版信息
PLoS One. 2014 May 8;9(5):e96542. doi: 10.1371/journal.pone.0096542. eCollection 2014.
BACKGROUND
Serum concentrations of the tumor-associated folate receptor 1 (FOLR1) protein may be a marker for early cancer detection, yet concentrations have also been detected in cancer-free women. We investigated the conditions associated with circulating FOLR1 protein in healthy individuals and sought to clarify the range of normal serum values.
METHODS
Sera of cancer-free men and women (N = 60) enrolled in a population-based cohort study in Alberta, Canada were analyzed for FOLR1 protein using an electrochemical luminescence immunoassay. Dietary, lifestyle, medical and reproductive history information was collected by questionnaires. Differences in serum FOLR1 concentrations between groups were assessed by non-parametric tests, and predictors of serum FOLR1 concentrations were estimated using multivariable linear regression.
RESULTS
Median serum FOLR1 concentration was higher in women (491 pg/ml, range = 327-693 pg/ml) than in men (404 pg/ml, range = 340-682 pg/ml), P = 0.001. FOLR1 concentration was also positively associated with vitamin A intake (P = 0.02), and showed positive trends with age and with oral contraceptive hormone use among women and an inverse trend with body mass index. All variables examined explained almost half of the variation in serum FOLR1 (model R2 = 0.44, P = 0.04); however, the retention of gender (P = 0.003) and vitamin A intake (P = 0.03) together explained 20% (P = 0.001) of serum FOLR1 variation. No other predictor was significant at P<0.05.
CONCLUSIONS
The positive association between serum FOLR1 concentration and female gender independent of an age effect suggests caution against statements to exploit serum FOLR1 for early cancer detection without further understanding the biological underpinnings of these observations. Serum FOLR1 concentrations may be influenced by the steroid retinoic acid (vitamin A) but do not appear to be associated with folate nutritional status. These findings require confirmation in larger independent studies.
背景
肿瘤相关叶酸受体1（FOLR1）蛋白的血清浓度可能是早期癌症检测的标志物，但在未患癌症的女性中也检测到了该浓度。我们调查了健康个体中循环FOLR1蛋白相关的情况，并试图明确正常血清值的范围。
方法
采用电化学发光免疫分析法对加拿大艾伯塔省一项基于人群的队列研究中纳入的无癌男性和女性（N = 60）的血清进行FOLR1蛋白分析。通过问卷调查收集饮食、生活方式、医疗和生殖史信息。采用非参数检验评估各组间血清FOLR1浓度的差异，并使用多变量线性回归估计血清FOLR1浓度的预测因素。
结果
女性血清FOLR1浓度中位数（491 pg/ml，范围 = 327 - 693 pg/ml）高于男性（404 pg/ml，范围 = 340 - 682 pg/ml），P = 0.001。FOLR1浓度也与维生素A摄入量呈正相关（P = 0.02），在女性中与年龄和口服避孕药激素使用呈正趋势，与体重指数呈负趋势。所有检测变量解释了血清FOLR1几乎一半的变异（模型R2 = 0.44，P = 0.04）；然而，性别（P = 0.003）和维生素A摄入量（P = 0.03）共同解释了血清FOLR1变异的20%（P = 0.001）。在P<0.05时，没有其他预测因素具有显著性。
结论
血清FOLR1浓度与女性性别呈正相关，且不受年龄影响，这表明在未进一步了解这些观察结果的生物学基础之前，谨慎对待利用血清FOLR1进行早期癌症检测的说法。血清FOLR1浓度可能受类固醇视黄酸（维生素A）影响，但似乎与叶酸营养状况无关。这些发现需要在更大规模的独立研究中得到证实。
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