Reyes-Gibby Cielito C, Spitz Margaret, Wu Xifeng, Merriman Kelly, Etzel Carol, Bruera Eduardo, Kurzrock Razelle, Shete Sanjay
Department of Epidemiology, Division of Cancer Prevention, The University of Texas M.D. Anderson Cancer Center, Unit 1340, 1155 Pressler Street, Houston, TX 77030-4009, USA.
Cancer Epidemiol Biomarkers Prev. 2007 Dec;16(12):2745-51. doi: 10.1158/1055-9965.EPI-07-0651.
Cytokines, aberrantly produced by cancer cells, have recently been implicated in the severity of cancer-related pain. We explored if polymorphisms in candidate cytokine genes could explain variability in self-reported pain in lung cancer patients of all stages.
Pain, clinical, and demographic variables were assessed at presentation and before any cancer treatment in 446 Whites, 125 African-Americans, and 35 Hispanics with newly diagnosed non-small cell lung cancer. We genotyped functional single nucleotide polymorphisms in tumor necrosis factor-alpha (TNF-alpha -308 G/A), interleukin-6 (IL-6) -174G/C, and IL-8 -251T/A and determined their associations with pain severity.
More African-Americans (35.5%) reported severe pain (score > or = 7 on a 0-10 scale) relative to Hispanics (20%) and Whites (17%; P < 0.001). We did not observe any significant association between genotypes in TNF-alpha, IL-6, and IL-8 and severe pain for either African-Americans or Hispanics, possibly due to small sample sizes. However, we observed that IL-8 (TT, 13%; TA + AA, 87%; P = 0.04) was significantly associated with severe pain among White patients. Logistic regression analyses showed that after controlling for epidemiologic (age and sex), clinical (stage of disease, comorbidities), and symptom (depressed mood and fatigue) variables known to influence pain severity, variant alleles in IL-8 -251T/A [odds ratio (OR), 2.35; 95% confidence interval (95% CI), 1.10-5.03; P = 0.03] persisted as a significant factor for severe pain for White patients.
In this preliminary analysis, we found evidence of the influence of cytokine genes on pain in White patients with lung cancer. Additional larger studies are needed to validate our findings. The long-term application is to tailored pain therapies.
癌细胞异常产生的细胞因子最近被认为与癌症相关疼痛的严重程度有关。我们探讨了候选细胞因子基因中的多态性是否可以解释各阶段肺癌患者自我报告疼痛的变异性。
对446名白人、125名非裔美国人以及35名西班牙裔新诊断的非小细胞肺癌患者在就诊时及任何癌症治疗前评估疼痛、临床和人口统计学变量。我们对肿瘤坏死因子-α（TNF-α -308 G/A）、白细胞介素-6（IL-6）-174G/C和IL-8 -251T/A中的功能性单核苷酸多态性进行基因分型，并确定它们与疼痛严重程度的关联。
与西班牙裔（20%）和白人（17%）相比，更多的非裔美国人（35.5%）报告有严重疼痛（0至10分的评分≥7分；P<0.001）。对于非裔美国人或西班牙裔，我们未观察到TNF-α、IL-6和IL-8的基因型与严重疼痛之间存在任何显著关联，这可能是由于样本量较小。然而，我们观察到，在白人患者中，IL-8（TT，13%；TA+AA，87%；P=0.04）与严重疼痛显著相关。逻辑回归分析表明，在控制了已知会影响疼痛严重程度的流行病学（年龄和性别）、临床（疾病分期、合并症）和症状（情绪低落和疲劳）变量后，IL-8 -251T/A中的变异等位基因[比值比（OR），2.35；95%置信区间（95%CI），1.10 - 5.03；P=0.03]仍然是白人患者严重疼痛的一个重要因素。
在这项初步分析中，我们发现了细胞因子基因对白人肺癌患者疼痛有影响的证据。需要更多更大规模的研究来验证我们的发现。长期应用在于定制疼痛治疗方案。
