Associations Between Preoperative Shortness of Breath and Potassium Channels Gene Variations in Women With Breast Cancer

Objectives: Shortness of breath is a common symptom in patients with cancer. However, the mechanisms that underlie this troublesome symptom are poorly understood. Therefore, this study aimed to determine the prevalence of and associated risk factors for shortness of breath in women prior to breast cancer surgery and identify associations between shortness of breath and polymorphisms for potassium channel genes.

Methods: Patients were recruited prior to breast cancer surgery and completed a self-report questionnaire on the occurrence of shortness of breath. Genotyping of single nucleotides polymorphism (SNPs) in potassium channel genes was performed using a custom array. Multiple logistic regression analyses were done to identify associations between the occurrence of shortness of breath and SNPs in ten candidate genes.

Results: Of the 398 patients, 11.1% reported shortness of breath. These patients had a lower annual household income, a higher comorbidity burden, and a lower functional status. After controlling for functional status, comorbidity burden, genomic estimates of ancestry and self-reported race and ethnicity, the genetic associations that remained significant in the multiple regression analyses were for potassium voltage-gated channel subfamily D (KCND2) rs12673992, potassium voltage-gated channel modifier subfamily S (KCNS1) rs4499491, and potassium two pore channel subfamily K (KCNK2) rs4411107.

Conclusions: While these findings warrant replication, they suggest that alterations in potassium channel function may contribute to the occurrence of shortness of breath in women prior to breast cancer surgery.