Seasonal and geographical variations in lung cancer prognosis in Norway Does Vitamin D from the sun play a role?
Seasonal and geographical variations in lung cancer prognosis in Norway Does Vitamin D from the sun play a role?
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DOI：
10.1016/j.lungcan.2006.11.013
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发表时间：
2007-03-01
期刊：
影响因子：
5.3
通讯作者：
Moan, Johan
中科院分区：
文献类型：
--
作者：
Porojnicu, Alina Carmen;Robsahm, Trude Eid;Moan, Johan
维生素D衍生物可以调节癌细胞的增殖和分化。我们的维生素D的主要来源是紫外线（UV）辐射诱导的合成后，皮肤暴露在阳光下。紫外线测量显示，挪威从北到南每年的环境紫外线暴露增加了约50%。从鳞状细胞癌的发病率来看，个人紫外线照射的平均水平也是如此。太阳紫外线B (UVB) （280 ~ 320 nm）表现出强烈的季节变化，在冬季最小。目前的工作旨在调查影响维生素D水平的诊断季节和居住区域对挪威诊断的肺癌患者死亡风险的影响。收集了1964年至2000年间所有肺癌病例的数据。风险估计以相对危险度（RR）计算，95%置信区间采用Cox回归模型。25-羟基维生素D的季节性变化通过在阿克大学医院激素实验室进行的15616个样本的常规测量来评估。我们的研究结果表明，诊断季节对肺癌患者具有预后价值，在秋季诊断的年轻配偶患者的病死率比冬季低约15% （RR = 0.85; 95% CI, -0.73至0.99;p = 0.04）。居住在高紫外线地区比居住在低紫外线地区的死亡风险更高。我们提出，与前列腺癌、乳腺癌、结肠癌和霍奇金淋巴瘤的早期研究结果一致，高水平的太阳诱导的25-羟基维生素D可能是某些肺癌患者群体的预后优势，尤其是年轻男性。几十年来，肺癌一直是挪威男性癌症相关死亡的主要原因，在过去二十年中，肺癌已成为女性癌症相关死亡的第二大常见原因。肺癌主要有两种类型：以化疗为主要治疗手段的小细胞肺癌和以手术为主要治疗手段的非小细胞肺癌。性别相关的差异已经在文献中描述了治疗后的生存，配偶性别是一个重要的独立负面预后因素[3]。在挪威，女性局部肿瘤的5年相对存活率约为30%，男性为20%。骨化三醇是维生素D最活跃的形式，参与多种细胞的增殖、分化和凋亡等关键调控过程[4-6]。这些作用的机制被认为是活性维生素D衍生物与特定的核受体（VDR受体）和/或膜靶点的相互作用[4,7]。对肺癌细胞系进行的体外研究表明，维生素D衍生物对细胞生长和增殖有抑制作用。此外，动物研究已经证明这些化合物能够抑制体内的侵袭、转移和血管生成[9-11]，这表明维生素D衍生物可能被用作肺癌的辅助治疗。人类通过暴露在阳光下或人工紫外线B （UVB, 280-320 nm）源下获得最佳的维生素D水平，也可能通过食用富含这种营养素的食物（脂肪鱼，鸡蛋，人造黄油等）或维生素补充剂[13]。在这些来源中，太阳辐射似乎是最重要的来源。因此，维生素D状态（通过血清25-羟基维生素D、钙二醇水平评估）表现出强烈的季节性变化，与到达地面的太阳UVB影响的季节性变化相似。在冬季，北欧国家（北纬50-71度）的中波紫外线照射率低于皮肤合成维生素D所需的水平。钙二醇在7月至9月达到最大值，比相应的冬季水平高出20-120%[15-24]。最近，我们假设在挪威，钙二醇的季节变化可能对结肠癌、乳腺癌、前列腺癌以及霍奇金淋巴瘤具有预后意义。夏季和秋季确诊的患者在标准治疗后的生存率高于冬季确诊的患者[25,26]。这可能是维生素D水平较高的结果。美国的一项研究调查了手术季节和近期维生素D摄入量对非小细胞肺癌患者生存的影响。作者报道，与冬季和低维生素D摄入量相比，夏季和高维生素D摄入量具有显著的有益联合效应。最近在英国进行的一项大型研究也报告了类似的结果，该研究涉及100多万癌症患者，其中包括19万多名被诊断患有肺癌的患者。挪威（北纬58-71度）的紫外线通量南北差异显著。这使得该国适合进行将癌症流行病学与紫外线水平联系起来的研究[29,30]。我们研究了紫外线的变化，因此。维生素D水平对肺癌预后的影响，以诊断季节和居住地区为变量。研究人员将40年间确诊患者的生存数据与阿克大学医院激素实验室1996-2001年期间常规测量的血清维生素D水平变化进行了比较。从分析中可以估计出维生素D水平的季节性和性别差异。2006爱思唯尔爱尔兰有限公司版权所有。
Vitamin D derivatives can modulate proliferation and differentiation of cancer cells. Our main source of Vitamin D is ultraviolet (UV) radiation-induced synthesis in skin following sun exposure. UV measurements show that the ambient annual UV exposures increase by about 50% from north to south in Norway. As judged from the incidence rates of squamous cell carcinoma, the same is true for the average personal UV exposures. Solar ultraviolet B (UVB) (280-320 nm) exhibits a strong seasonal variation with a minimum during the winter months. The present work aims at investigating the impact of season of diagnosis and residential region, both influencing the Vitamin D level, on the risk of death from lung cancer in patients diagnosed in Norway.Data on all incident cases of lung cancer between 1964 and 2000 were collected. Risk estimates were calculated as relative risk (RR), with 95% confidence intervals using Cox regression model. The seasonal variation of 25-hydroxyvitamin D was assessed from routine measurements of 15,616 samples performed at The Hormone Laboratory of Aker University Hospital.Our results indicate that season of diagnosis is of prognostic value for lung cancer patients, with a approximate to 15% lower case fatality for young mate patients diagnosed during autumn versus winter (RR = 0.85; 95% CI, -0.73 to 0.99; p = 0.04). Residing in a high UV region resulted in a further towering of the death risk than residing in a tow UV region.We propose, in agreement with earlier findings for prostate-, breast- colon cancer and Hodgkins lymphoma, that a high level of sun-induced 25-hydroxyvitamin D can be a prognostic advantage for certain groups of lung cancer patients, notably for young men.Lung cancer has for several decades been the leading cause of cancer-related mortality in men in Norway [1] and during the last two decades, became the second most common cause of cancer-related death in women [2]. There are two main types of lung cancer: small cell lung cancer for which chemotherapy is the primary treatment and non-small cell lung cancer, which in its early stages is treated primarily with surgery. Gender-related differences have been described in the literature with respect to survival after therapy, mate gender being a significant independent negative prognostic factor [3]. In Norway the 5 years relative survival for localized tumours is about 30% for females and 20% for mates.Calcitriol, which is the most active form of Vitamin D, is involved in key regulatory processes such as proliferation, differentiation and apoptosis in a wide variety of cells [4-6]. Mechanisms for these actions have been proposed to be the interaction of active Vitamin D derivatives with a specific nuclear receptor (VDR receptor) and/or with membrane targets [4,7]. In vitro studies, performed with lung cancer cell lines, have shown an inhibitive effect of Vitamin D derivatives on cell-growth and proliferation [8]. Furthermore, animal studies have demonstrated the capability of these compounds to suppress invasion, metastasis and angiogenesis in vivo [9-11], suggesting that administration of Vitamin D derivatives may be used as adjuvant therapy for lung cancer.Humans get optimal Vitamin D levels by exposure to sun or artificial ultraviolet B (UVB, 280-320 nm) sources [12], and possibly also by consumption of food rich in this nutrient (fat fish, eggs, margarine, etc.) or of vitamin supplements [13]. Among these sources, solar radiation appears to be the most important one [12]. Thus, the Vitamin D status (assessed by the serum levels of 25-hydroxyvitamin D, calcidiol) exhibits a strong seasonal variation that parallels the seasonal change in the fluence of solar UVB that reaches the ground. During winter, the UVB fluence rate in the Nordic countries (50-71 degrees N) is below the level required for Vitamin D synthesis in skin [14]. The maximal level of calcidiol is reached between the months July and September, and is 20-120% higher than the corresponding winter level [15-24].Recently we hypothesised that the seasonal variation of calcidiol might be of prognostic significance for colon-, breast- prostate cancer as well as for Hodgkins lymphoma in Norway. Patients diagnosed during summer and autumn have a better survival after standard treatment than patients diagnosed during the winter season [25,26]. This might be a consequence of a higher Vitamin D level. An American study investigated the effect of season of surgery and recent Vitamin D intake on the survival of non-small cell lung cancer patients. The authors reported a significant beneficial joint effect of summer season and high Vitamin D intake compared with winter season and low Vitamin D intake [27] white Vitamin D intake alone did not affect prognosis. Similar results were recently reported from a large study in United Kingdom involving over a million cancer patients including over 190,000 patients diagnosed with lung cancer [28].Norway (58-71 degrees N) has a significant north-south variation in UV fluence. This makes the country suitable for studies relating cancer epidemiology to UV levels [29,30].We investigated whether variations in UV, and, consequently. in Vitamin D level, influence the prognosis of lung cancer, using season of diagnosis and residential regions as variables. Survival data obtained for patients diagnosed over a 40 years period were compared with variations in serum Vitamin D levels obtained from routine measurements performed in The Hormone Laboratory of Aker University Hospital during the period 1996-2001. Seasonal and gender variations in Vitamin D level have been estimated from the analyses. (c) 2006 Elsevier Ireland Ltd. All rights reserved.