Genetic predictors of response to acupuncture for aromatase inhibitor-associated arthralgia among breast cancer survivors

Abstract

Objective. To evaluate the associations between polymorphisms in two genes, catechol-O-methyltransferase and T-cell leukemia/lymphoma 1 A, and acupuncture-mediated pain reduction among breast cancer survivors with aromatase inhibitor-associated arthralgia. Design, Setting, and Subjects. Biospecimens were obtained from 38 patients enrolled in a clinical trial of acupuncture for aromatase inhibitor-associated arthralgia in postmenopausal hormone receptor-positive breast cancer survivors. Methods. We used polymerase chain reaction to genotype the rs4680 (Val158Met) and rs4633 (His62His) variants in the catechol-O-methyltransferase gene and rs2369049 (A > G) and rs7158782 (A > G) variants in the T-cell leukemia/ lymphoma 1 A gene. Response to acupuncture was defined by 30% reduction in end-of-treatment average pain, measured by the Brief Pain Inventory. We used Fisher exact tests to evaluate associations between genotype and treatment response. Results. Among participants, all six (15.8%) subjects who expressed AA in locus rs4680 responded to acupuncture. In a combined analysis, the 18 (47.4%) subjects with the responder genotype at either rs4680 (AA) or rs2369049 (GG or AG) were significantly more likely to respond to acupuncture than those without (77.8% vs 45.0%, P 5 0.039). Conclusions. Specific genetic variations at loci rs4680 and rs2369049 are associated with response to acupuncture-type intervention for management of arthralgia. These results serve as a proof of concept for applying a precision medicine framework to the study of cancer pain management.