铁水平、铁代谢和抗氧化过程相关基因与肺癌发病率。
Iron levels, genes involved in iron metabolism and antioxidative processes and lung cancer incidence.
机构信息
Department of Genetics and Pathology, International Hereditary Cancer Center, Pomeranian Medical University, Szczecin, Poland.
Read- Gene S.A., Grzepnica, Dobra Szczecińska, Poland.
出版信息
PLoS One. 2019 Jan 14;14(1):e0208610. doi: 10.1371/journal.pone.0208610. eCollection 2019.
BACKGROUND
Lung cancer is the most common adult malignancy accounting for the largest proportion of cancer related deaths. Iron (Fe) is an essential trace element and is a component of several major metabolic pathways playing an important role in many physiological processes. In this study we evaluated the association between Fe concentration in serum, iron metabolism parameters and genetic variaton in 7 genes involved in iron metabolism and anti-oxidative processes with the incidence of lung cancer in Poland.
MATERIALS AND METHODS
The study included 200 lung cancer patients and 200 matched healthy control subjects. We analyzed serum iron concentration and iron metabolism parameters (TIBC, UIBC, serum ferritin and transferrin saturation), and genotyped seven variants in seven genes: HFE, TFR1, HAMP, TF, SOD2, CAT and GPX1.
RESULTS
Lung cancer patients compared to their matched controls had significantly higher mean serum iron level (p = 0.01), ferritin level (p = 0.007) and TIBC (p = 0.006). Analysis revealed that higher concentration of iron and ferritin (IVth quartile) compared to the lower concentration (Ist quartile) was associated with over 2-fold increased lung cancer incidence. We also found that higher transferrin saturation (p = 0.01) and lower TIBC (p<0.01) are associated with better survival of lung cancer patients. The analysis of polymorphisms in iron related genes did not reveal a significant difference between lung cancer patients and controls. However, rs10421768 in HAMP showed a borderline statistically significant correlation with lung cancer risk (OR = 2.83, p = 0.05).
CONCLUSIONS
The results of this case control study indicate that higher body iron represented by higher Fe and ferritin levels may be associated with lung cancer incidence. Rs10421768 in HAMP may be associated with about 3-times higher lung cancer risk. Higher Fe body content may be associated with better survival of lung cancer patients.
背景
肺癌是最常见的成人恶性肿瘤，占癌症相关死亡人数的比例最大。铁（Fe）是一种必需的微量元素，是几个主要代谢途径的组成部分，在许多生理过程中发挥着重要作用。在这项研究中，我们评估了血清铁浓度、铁代谢参数以及与铁代谢和抗氧化过程相关的 7 个基因中的遗传变异与波兰肺癌发病率之间的关系。
材料和方法
该研究包括 200 名肺癌患者和 200 名匹配的健康对照者。我们分析了血清铁浓度和铁代谢参数（TIBC、UIBC、血清铁蛋白和转铁蛋白饱和度），并对 7 个基因中的 7 个变体进行了基因分型：HFE、TFR1、HAMP、TF、SOD2、CAT 和 GPX1。
结果
与匹配的对照组相比，肺癌患者的平均血清铁水平（p = 0.01）、铁蛋白水平（p = 0.007）和 TIBC（p = 0.006）显著更高。分析表明，与较低浓度（I 四分位数）相比，铁和铁蛋白较高浓度（IV 四分位数）与肺癌发病率增加两倍以上相关。我们还发现，较高的转铁蛋白饱和度（p = 0.01）和较低的 TIBC（p<0.01）与肺癌患者的更好生存相关。铁相关基因多态性分析未显示肺癌患者与对照组之间存在显著差异。然而，HAMP 中的 rs10421768 与肺癌风险呈临界统计学显著相关性（OR = 2.83，p = 0.05）。
结论
这项病例对照研究的结果表明，较高的铁体代表较高的 Fe 和铁蛋白水平可能与肺癌的发病率有关。HAMP 中的 rs10421768 可能与肺癌风险增加约 3 倍有关。较高的 Fe 体含量可能与肺癌患者的更好生存有关。
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