Schools of Nursing, University of California, San Francisco, CA, USA Schools of Medicine, University of California, San Francisco, CA, USA Institute for Human Genetics, University of California, San Francisco, CA, USA.
Pain. 2015 Mar;156(3):371-380. doi: 10.1097/01.j.pain.0000460319.87643.11.
Persistent pain after breast cancer surgery is a common clinical problem. Given the role of potassium channels in modulating neuronal excitability, coupled with recently published genetic associations with preoperative breast pain, we hypothesized that variations in potassium channel genes will be associated with persistent postsurgical breast pain. In this study, associations between 10 potassium channel genes and persistent breast pain were evaluated. Using growth mixture modeling (GMM), 4 distinct latent classes of patients, who were assessed before and monthly for 6 months after breast cancer surgery, were identified previously (ie, No Pain, Mild Pain, Moderate Pain, Severe Pain). Genotyping was done using a custom array. Using logistic regression analyses, significant differences in a number of genotype or haplotype frequencies were found between: Mild Pain vs No Pain and Severe Pain vs No Pain classes. Seven single-nucleotide polymorphisms (SNPs) across 5 genes (ie, potassium voltage-gated channel, subfamily A, member 1 [KCNA1], potassium voltage-gated channel, subfamily D, member 2 [KCND2], potassium inwardly rectifying channel, subfamily J, members 3 and 6 (KCNJ3 and KCNJ6), potassium channel, subfamily K, member 9 [KCNK9]) were associated with membership in the Mild Pain class. In addition, 3 SNPs and 1 haplotype across 4 genes (ie, KCND2, KCNJ3, KCNJ6, KCNK9) were associated with membership in the Severe Pain class. These findings suggest that variations in potassium channel genes are associated with both mild and severe persistent breast pain after breast cancer surgery. Although findings from this study warrant replication, they provide intriguing preliminary information on potential therapeutic targets.
乳腺癌手术后持续性疼痛是一种常见的临床问题。鉴于钾通道在调节神经元兴奋性中的作用，以及最近发表的与术前乳房疼痛的遗传关联，我们假设钾通道基因的变异与持续性手术后乳房疼痛有关。在这项研究中，评估了 10 个钾通道基因与持续性乳房疼痛之间的关联。使用增长混合物建模（GMM），先前已经鉴定出 4 个具有不同潜在类别的患者，这些患者在乳腺癌手术后进行了评估，每月评估一次，共 6 个月（即无疼痛、轻度疼痛、中度疼痛、重度疼痛）。使用定制的数组进行基因分型。使用逻辑回归分析，在轻度疼痛与无疼痛以及重度疼痛与无疼痛组之间发现了许多基因型或单倍型频率的显著差异。在 5 个基因（即钾电压门控通道，亚家族 A，成员 1[KCNA1]，钾电压门控通道，亚家族 D，成员 2[KCND2]，钾内向整流通道，亚家族 J，成员 3 和 6[KCNJ3 和 KCNJ6]，钾通道，亚家族 K，成员 9[KCNK9]）中，7 个单核苷酸多态性（SNP）与轻度疼痛组的成员身份相关。此外，在 4 个基因（即 KCND2、KCNJ3、KCNJ6、KCNK9）中，有 3 个 SNP 和 1 个单倍型与重度疼痛组的成员身份相关。这些发现表明，钾通道基因的变异与乳腺癌手术后的轻度和重度持续性乳房疼痛有关。尽管本研究的结果需要复制，但它们提供了关于潜在治疗靶点的有趣初步信息。
