Merriman John D, Aouizerat Bradley E, Cataldo Janine K, Dunn Laura, Cooper Bruce A, West Claudia, Paul Steven M, Baggott Christina R, Dhruva Anand, Kober Kord, Langford Dale J, Leutwyler Heather, Ritchie Christine S, Abrams Gary, Dodd Marylin, Elboim Charles, Hamolsky Deborah, Melisko Michelle, Miaskowski Christine
School of Nursing, University of Pittsburgh, 3500 Victoria Street, Pittsburgh, PA 15261, United States.
School of Nursing, University of California, San Francisco, 2 Koret Way, Box 0610, San Francisco, CA 94143, United States; Institute for Human Genetics, University of California, San Francisco, 513 Parnassus Avenue, Box 0794, San Francisco, CA 94143, United States.
Cytokine. 2014 Feb;65(2):192-201. doi: 10.1016/j.cyto.2013.11.003. Epub 2013 Dec 4.
Subgroups of patients with breast cancer may be at greater risk for cytokine-induced changes in cognitive function after diagnosis and during treatment. The purposes of this study were to identify subgroups of patients with distinct trajectories of attentional function and evaluate for phenotypic and genotypic (i.e., cytokine gene polymorphisms) predictors of subgroup membership. Self-reported attentional function was evaluated in 397 patients with breast cancer using the Attentional Function Index before surgery and for six months after surgery (i.e., seven time points). Using growth mixture modeling, three attentional function latent classes were identified: High (41.6%), Moderate (25.4%), and Low-moderate (33.0%). Patients in the Low-moderate class were significantly younger than those in the High class, with more comorbidities and lower functional status than the other two classes. No differences were found among the classes in years of education, race/ethnicity, or other clinical characteristics. DNA was recovered from 302 patients' samples. Eighty-two single nucleotide polymorphisms among 15 candidate genes were included in the genetic association analyses. After controlling for age, comorbidities, functional status, and population stratification due to race/ethnicity, IL1R1 rs949963 remained a significant genotypic predictor of class membership in the multivariable model. Carrying the rare "A" allele (i.e., GA+AA) was associated with a twofold increase in the odds of belonging to a lower attentional function class (OR: 1.98; 95% CI: 1.18, 3.30; p=.009). Findings provide evidence of subgroups of women with breast cancer who report distinct trajectories of attentional function and of a genetic association between subgroup membership and an IL1R1 promoter polymorphism.
乳腺癌患者亚组在诊断后及治疗期间可能因细胞因子导致认知功能变化的风险更高。本研究的目的是识别注意力功能轨迹不同的患者亚组,并评估亚组成员的表型和基因型(即细胞因子基因多态性)预测因素。在397例乳腺癌患者手术前及术后6个月(即7个时间点),使用注意力功能指数对自我报告的注意力功能进行评估。采用生长混合模型,识别出三种注意力功能潜在类别:高(41.6%)、中(25.4%)和低-中(33.0%)。低-中类别患者明显比高类别患者年轻,合并症更多,功能状态低于其他两个类别。在受教育年限、种族/民族或其他临床特征方面,各类别之间未发现差异。从302例患者样本中提取了DNA。基因关联分析纳入了15个候选基因中的82个单核苷酸多态性。在控制年龄、合并症、功能状态以及种族/民族导致的群体分层后,IL1R1 rs949963在多变量模型中仍然是亚组成员的显著基因型预测因素。携带罕见的“A”等位基因(即GA+AA)与属于较低注意力功能类别的几率增加两倍相关(OR:1.98;95%CI:1.18,3.30;p=0.009)。研究结果为报告注意力功能轨迹不同的乳腺癌女性亚组提供了证据,并证明了亚组成员与IL1R1启动子多态性之间的基因关联。