抽象的
白细胞端粒长度应包括在与肺癌相关的独立危险因素中http://ow.ly/uzlg304qpn6
致编辑:
端粒是DNA - 蛋白质结构,可保护染色体末端免受降解,并逐渐缩短每个细胞分裂[1]。
Telomere length measured in peripheral leukocytes has been used to determine an individual's “biological age”, and previous reports have demonstrated that patients with chronic obstructive pulmonary disease (COPD) and/or emphysema have shorter peripheral leukocyte telomere length [2-5]。COPD和肺气肿的存在是肺癌最终发展的独立危险因素[6,,,,7]。
The relationship between telomere length and lung cancer is controversial. Some reports have previously shown an increase in the risk for lung cancer development in subjects with shorter telomere length [8] but recent reports have described that smokers with longer peripheral leukocyte telomere length are also at increased risk [9]。
本研究探讨了周围白细胞端粒长度,COPD和肺气肿与肺癌诊断的潜在独立关联,这是对参与肺癌筛查计划的活跃和前吸烟者的前瞻性招募人群的横截面分析。
我们包括40岁或以上的男性和女性,他们是吸烟史≥10种包的现任或以前的吸烟者,并且没有肺癌筛查计划中的肺癌症状[6]。所有患者接受肺量测定法来确定the presence of airway obstruction (post bronchodilator value of forced expiratory volume in 1 s (FEV1)/强制生命能力(FVC)<0.70)和低剂量胸部计算机断层扫描以确定肺气肿的存在(视觉检测为是相对no).
从1681名受试者参加的受试者(有多次访问的受试者)参加我们的筛查计划中,我们有来自1256名活跃或以前吸烟者的血液样本。其中,314符合COPD的肺活量测定标准。从这个池中,我们随机选择了其中125个参加本研究。我们与这些患者中的每一名都有活跃或以前的吸烟者,没有年龄相似的COPD(±2岁),性别,包装 - 年历史(±3包),吸烟状态和体重指数(BMI)(±2)(±2) kg·m-2)。Relative telomere length was assessed in peripheral leukocytes using the comparative Ct method (T/S=2−ΔΔCt) as previously described [10]。Cox regression analysis was used to explore the independent association of each predictive variable with lung cancer diagnosis. Predictor variables that were statistically significant (p<0.05) in the univariate analysis were included in a multiple Cox regression model to determine which of them independently related to lung cancer diagnosis. Calculations were made with SPSS version 20.0 Inc.
本研究中包括的患者主要是男性(85%),中年(平均年龄:60岁),略有超重(平均BMI在27 kg·m之间-2),具有较高的包装历史(平均40包),而其中很大比例积极吸烟(60%和65%)。正如匹配人群所预期的那样,在群体之间没有发现年龄,性别,包装或吸烟状态的年龄,性别,包装或吸烟状态的差异。COPD患者的BMI和肺活量测定值低于对照。90%的COPD患者患有轻度至中度气道阻塞。在有或没有COPD的活性和前吸烟者或患有和没有肺气肿的人之间,在活性和前吸烟者之间没有发现差异。在52个月的中位随访时间中,COPD患者的比例明显更高,被诊断出患有肺癌(26%相对5%;p = 0.001)。
评估每个因素与肺癌诊断的独立关联的单变量COX分析显示在表格1。一个s expected, more pack–years, a lower BMI, the presence of COPD or of radiologically detected emphysema, were associated with lung cancer. Patients in the quartile characterised by having the longest telomere length were most likely to have lung cancer. In the Cox multivariate analysis detailed in table 1, pack–years, the presence of COPD or of emphysema and longer telomere length quartile remained as independent predictors of lung cancer.
The present cross-sectional study showed that lung cancer screening participants with longer peripheral leukocyte telomere length have a higher risk of developing lung cancer, independent of the presence of COPD or radiological emphysema. This finding is interesting since these two diseases have been traditionally described as part of early and accelerated ageing processes associated with shorter telomere length [2]并增加肺癌风险[6,,,,7]。
jang等。[[8]首先假定较短的外周白细胞端粒长度和肺癌风险之间的联系。他们研究了243例肺癌患者和243例相似年龄,性别和吸烟状况的健康对照,发现较短的端粒长度(以四分位数或中位数测量)与更高的肺癌风险相关。m一个等。[[11]后来进行了荟萃分析,探索了11个255例病例的数据集和21个出版物中的13个101个对照,这也表明较短的端粒与较高的肺癌风险显着相关(OR 2.39,95%CI 1.18-4.88)。
However, two recent studies have reported opposite findings. M一个chiela等。[[9]研究了一组来自前瞻性上海妇女健康研究(SWHS)的1536名个人,发现较长的端粒长度与肺癌风险增加有关(OR 1.51,95%CI 1.34–1.69)。seow等。[[12] explored a pool analysis of subjects from the Prostate, Lung, Colorectal and Ovarian (PLCO) Cancer Screening Trial, the Alpha-Tocopherol, Beta-Carotene Cancer Prevention (ATBC) Trial and the SWHS and demonstrated that patients with the longest peripheral leukocyte telomere length had the highest risk for lung cancer. Importantly, none of these studies assessed the potential risk associated with the presence of COPD and/or emphysema. The current study provides a novel perspective of the most important risk factors associated with lung cancer by including into the analysis, the concurrent presence of COPD or emphysema as independent factors that could help explain the differences observed in previous studies.
稀缺信息可解释长端粒长度和癌症风险之间的关联。最近,一些报道证明,延长端粒的突变与癌症的风险增加有关,例如黑色素瘤和神经胶质瘤。这些报告表明,该机制可能与端粒酶和庇护基因的突变有关,该机制称为“长端粒综合征” [13]。途径尚未完全定义,但似乎是某些组织学类型的癌症的原因,其中大多数有关黑色素瘤发育的信息。有趣的是,Z的最新报告悬挂等。[[14]使用有关51 725例和62个035个对照的组织数据,应用了Mendelian随机化方法,并估计了9个端粒长度相关的SNP和五种常见癌症类型的风险(乳腺癌,肺,结直肠癌,卵巢癌),包括亚型,)。他们发现,在孟德尔随机化假设下,较长的端粒长度增加了肺腺癌的风险。此信息很重要,因为我们有55%的肺癌病例是腺癌,这与这些作者提出的假设一致。
本研究有几个局限性。首先,这是一个横截面分析,因此无法证明有效关系。其次,该研究并非旨在探索这种关联背后的机械途径。未来的研究应探索端粒酶活性测量和庇护基因突变,以解释这一新发现。第三,令人惊讶的是,我们找不到有和没有COPD的吸烟者之间的端粒长度差异。这是一个匹配良好的人群,相对年轻的吸烟者,年龄,性别,包装历史和吸烟状况以及相对较小的样本量,这一事实可以解释两组之间端粒长度的差异。但是,这一结果进一步增强了与探索变量显着关联的结果,而不是由于肺气肿或COPD引起的。
In summary, active or former smokers participating in a lung cancer screening programme with peripheral leukocytes’ telomere length in the longest quartile have an increased risk of lung cancer, independently of the presence of COPD or emphysema, two well-known lung cancer risk factors associated with shorter telomere length. Peripheral leukocyte telomere length should be included among the independent factor associated with lung cancer risk.
Disclosures
supplementary Material
J.J.ZuluetaeRJ-01521-2016_Zulueta
一个cknowledgements
J.P. De-Torres,G。Bastarrika,J.J。Zulueta,P。Sanchez-Salcedo,B.R。Celli(构思和设计,分析和解释,并起草重要知识内容的手稿);A.B.Alcaide,J。Berto,A。Campo,M。DelMar Ocon,C。Monente,R。Pío,M.J。Pajares,L。Montuenga(分析与解释)。
脚注
支持声明:这项工作部分得到了Red Tematica de Respejioncion cooperativa en Cancer,Salud Carlos III的赠款(RD12/0036/0062)的部分支持Manera de Hacer Europa”;以及赠款PI04/2404,PI07/0792,PI10/01652,PI11/01626,PI15/02157 SALUD CARLOS III Instituto de Salud Carlos III,西班牙政府经济和竞争力部。本文的资金信息已存入开放筹款机注册表。
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- 已收到2016年7月28日。
- 公认2016年9月28日。
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