癌症患者白细胞介素-1β基因型与循环水平：转移状态和疼痛感知
Interleukin-1β genotype and circulating levels in cancer patients: metastatic status and pain perception.
作者信息
Oliveira Ana, Dinis-Oliveira Ricardo J, Nogueira Augusto, Gonçalves Ferraz, Silva Paula, Vieira Cláudia, Silvestre Ricardo, Carvalho Félix, Medeiros Rui
机构信息
REQUIMTE, Laboratory of Toxicology, Department of Biological Sciences, Faculty of Pharmacy, University of Porto, Porto, Portugal; Molecular Oncology GRP and Virology LB, Portuguese Institute of Oncology-Porto, Porto, Portugal; IINFACTS - Institute of Research and Advanced Training in Health Sciences and Technologies, Department of Sciences, Advanced Institute of Health Sciences - North, CESPU, CRL, Gandra, Portugal.
REQUIMTE, Laboratory of Toxicology, Department of Biological Sciences, Faculty of Pharmacy, University of Porto, Porto, Portugal; IINFACTS - Institute of Research and Advanced Training in Health Sciences and Technologies, Department of Sciences, Advanced Institute of Health Sciences - North, CESPU, CRL, Gandra, Portugal; Department of Legal Medicine and Forensic Sciences, Faculty of Medicine, University of Porto, Porto, Portugal; Center of Forensic Sciences (CENCIFOR), Portugal.
出版信息
Clin Biochem. 2014 Sep;47(13-14):1209-13. doi: 10.1016/j.clinbiochem.2014.04.009. Epub 2014 Apr 18.
OBJECTIVES
Proinflammatory cytokines released during inflammation can cause hyperexcitability in pain transmission neurons, leading to hyperalgesia and allodynia. Polymorphisms in interleukin 1 (IL-1) family of genes (IL1A, IL1B) and in IL-1 receptor antagonist (IL-1Ra, coded by IL1RN) may therefore induce alterations in cytokine levels/effects and pain related response. Our purpose was to investigate the influence of polymorphisms in IL1A/B/RN on cytokine serum levels and its correlation with pain intensity, performance status, adverse effects, metastases and breakthrough pain in Caucasian cancer patients.
DESIGN AND METHODS
Serum IL-1α/β levels of 74 cancer patients were measured by competitive enzyme immunosorbent assay. All patients were also genotyped for the polymorphisms in IL1A (rs17561), IL1B (rs1143634) and IL1RN (rs419598) with Real-Time PCR. Results were then correlated to the appearance of bone or CNS metastases and several pain-related parameters.
RESULTS
IL-1β rs1143634 homozygous for T allele were associated with lower levels of IL1-β (p=0.032, Mann-Whitney test) and presented a trend for lower levels of pain (p=0.06, Fisher's Exact Test). Also, IL1-β levels were related with cancer onset status, since a four-fold increase probability of metastatic disease was observed in high IL-1β individuals (OR=4.074, p=0.010, Pearson χ(2) test). Among the female patients presenting metastatic disease and carriers of the TT genotype we observed a trend to lower levels of IL1-β (p=0.053, Pearson χ(2) test).
CONCLUSIONS
Our results indicate that genetic variation at IL1-β gene may influence serum levels of IL1-β, with proportional consequences in cancer-related pain.
目的
炎症过程中释放的促炎细胞因子可导致疼痛传递神经元的兴奋性过高，从而引起痛觉过敏和异常性疼痛。因此，白细胞介素1（IL-1）基因家族（IL1A、IL1B）和IL-1受体拮抗剂（IL-1Ra，由IL1RN编码）中的多态性可能会导致细胞因子水平/效应及疼痛相关反应的改变。我们的目的是研究IL1A/B/RN基因多态性对高加索癌症患者细胞因子血清水平的影响及其与疼痛强度、体能状态、不良反应、转移和爆发性疼痛的相关性。
设计与方法
采用竞争性酶联免疫吸附测定法测量74例癌症患者的血清IL-1α/β水平。所有患者还通过实时聚合酶链反应对IL1A（rs17561）、IL1B（rs1143634）和IL1RN（rs419598）基因多态性进行基因分型。然后将结果与骨转移或中枢神经系统转移的出现以及几个疼痛相关参数进行关联分析。
结果
IL-1β rs1143634 T等位基因纯合子与较低水平的IL-1β相关（p=0.032，曼-惠特尼检验），并且呈现出较低疼痛水平的趋势（p=0.06，费舍尔精确检验）。此外，IL-1β水平与癌症发病状态相关，因为在高IL-1β个体中观察到转移性疾病的发生概率增加了四倍（OR=4.074，p=0.010，Pearson卡方检验）。在患有转移性疾病且为TT基因型携带者的女性患者中，我们观察到IL-1β水平有降低的趋势（p=0.053，Pearson卡方检验）。
结论
我们的结果表明，IL-1β基因的遗传变异可能会影响IL-1β的血清水平，并对癌症相关疼痛产生相应影响。
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