Associations Between Catecholaminergic and Serotonergic Genes and Persistent Breast Pain Phenotypes After Breast Cancer Surgery

Abstract

Genetic variations in the catecholaminergic and serotonergic pathways may contribute to the development and severity of persistent breast pain. However, investigations of these associations are limited. The purpose of this study was to evaluate for associations between breast pain phenotypes and single nucleotide polymorphisms among 15 genes involved in catecholaminergic and serotonergic neurotransmission. Women rated the presence and intensity of breast pain monthly for 6 months after breast cancer surgery. Distinct latent classes of patients were identified using growth mixture modeling. Logistic regression analyses identified significant differences between genotype or haplotype frequencies and the breast pain classes (ie, no breast pain [n = 96] vs mild breast pain [n = 141], moderate breast pain [n = 46], and severe breast pain [n = 27]). Polymorphisms in 5 genes were associated with membership in the mild pain class: ** beta-2-adrenergic receptor (ADRB2) rs2400707, beta adrenergic receptor kinase 2 (ADRBK2) HapA04, 5-hydroxytryptamine receptor 3A (HTR3A) rs10160548, solute-like carrier (SLC) family 6 member 2–noradrenaline transporter (SLC6A2) rs1566652, and tryptophan hydroxylase 2 (TPH2) rs11179000. Polymorphisms in 3 genes were associated with membership in the moderate pain class: 5-hydroxytryptamine receptor 2A (HTR2A) rs2296972, SLC6A2 rs17841327, and SLC6A3 rs403636. Polymorphisms in 3 genes were associated with membership in the severe pain class: COMT HPS haplotype, SLC family 6 member 2–noradrenaline transporter (SLC6A2) HapD01, and SLC family 6 member 3–noradrenaline transporter (SLC6A3) rs464049. The identification of these associations suggest possible underlying mechanisms that play a role in the development and severity of persistent breast pain. Perspective: Findings from this study of women with breast cancer suggest that a number of catecholaminergic and serotonergic mechanisms may play a role in the development and severity of persistent breast pain phenotypes after surgery.