Shi Qiuling, Wang Xin Shelley, Li Guojun, Shah Nina D, Orlowski Robert Z, Williams Loretta A, Mendoza Tito R, Cleeland Charles S
Department of Symptom Research, The University of Texas MD Anderson Cancer Center, Houston, Texas.
Cancer. 2015 Apr 1;121(7):1138-46. doi: 10.1002/cncr.29154. Epub 2014 Dec 2.
This study was conducted to determine whether any regulatory single-nucleotide polymorphism (SNP) in an inflammatory gene was associated with a high symptom burden in patients 1 year after the diagnosis of multiple myeloma (MM).
MM patients rated symptoms with the MD Anderson Symptom Inventory multiple myeloma module (MDASI-MM) and provided buccal-swab DNA samples. SNPs for 4 cytokine genes (interleukin 6 [IL6] -174G>C, IL1β -511C>T, tumor necrosis factor α [TNFα] -308G>A, and IL10 -1082G>A) were tested. Logistic regression models were used to identify SNPs that might predict moderate/severe symptoms (rated ≥ 4 on the MDASI-MM 0-10 scale). For the evaluation of the relationship between SNPs and overall symptom burden, a 2-step cluster analysis was used to divide patients into subgroups with high or low symptom levels.
Forty-one percent of the 344 patients enrolled had a high overall symptom burden. The most prevalent moderate/severe symptoms were fatigue (47%), pain (42%), numbness (38%), and bone aches (32%). For non-Hispanic whites, the IL1β -511 CC genotype was associated with a high overall symptom burden (odds ratio [OR], 2.35; 95% confidence interval [CI], 1.25-4.72; P = .004), whereas the IL6 -174 GG genotype predicted less moderate/severe fatigue (OR, 0.53; 95% CI, 0.29-0.88; P = .013). For other patients, the IL6 -174 GG genotype predicted moderate/severe pain (OR, 3.36; 95% CI, 1.23-13.64; P = .010).
These results support growing evidence showing that inflammation is associated with cancer-related symptoms, and they suggest that racial/ethnic factors contribute to this association.
本研究旨在确定炎症基因中的任何调控单核苷酸多态性(SNP)是否与多发性骨髓瘤(MM)诊断后1年患者的高症状负担相关。
MM患者使用MD安德森症状问卷多发性骨髓瘤模块(MDASI-MM)对症状进行评分,并提供颊拭子DNA样本。对4种细胞因子基因(白细胞介素6 [IL6] -174G>C、白细胞介素1β [IL1β] -511C>T、肿瘤坏死因子α [TNFα] -308G>A和白细胞介素10 [IL10] -1082G>A)的SNP进行检测。使用逻辑回归模型来识别可能预测中度/重度症状(在MDASI-MM 0-10量表上评分≥4)的SNP。为了评估SNP与总体症状负担之间的关系,采用两步聚类分析将患者分为症状水平高或低的亚组。
344名入组患者中,41%的患者总体症状负担较高。最常见的中度/重度症状是疲劳(47%)、疼痛(42%)、麻木(38%)和骨痛(32%)。对于非西班牙裔白人患者,IL1β -511 CC基因型与总体症状负担较高相关(优势比[OR],2.35;95%置信区间[CI],1.25-4.72;P = 0.004),而IL6 -174 GG基因型预测中度/重度疲劳较少(OR,0.53;95% CI,0.29-0.88;P = 0.013)。对于其他患者,IL6 -174 GG基因型预测中度/重度疼痛(OR,3.36;95% CI,1.23-13.64;P = 0.010)。
这些结果支持越来越多的证据表明炎症与癌症相关症状有关,并且表明种族/民族因素促成了这种关联。