UCSF

Purpose: This study explores associations between variations in neurotransmitter genes and fatigue and energy levels in a sample of patients following breast cancer surgery. Variations in neurotransmitter genes between the Lower (n=153) and Higher (n=244) Fatigue latent classes as well as between the Higher (n=127) and Lower (n=270) Energy latent classes were evaluated.

Method: This analysis is part of a larger, longitudinal study that evaluated neuropathic pain and lymphedema in women who underwent breast cancer surgery. Patients completed baseline assessments at enrollment and monthly for 6 months following surgery. Growth mixture modeling (GMM) was used to identify distinct latent classes for fatigue severity and energy levels based on Lee Fatigue Scale (LFS) scores. A total of 30 candidate genes involved in various aspects of neurotransmission were evaluated.

Results: Ten genetic associations (i.e., ADRB2 rs1042718, BDNF rs6265, COMT rs9332377, CYP3A4 rs4646437, GALR1 rs949060, GCH1 rs3783642, NOS1 rs9658498, NOS1 rs2293052, NPYR1 Haplotype A04, and SLC6A2 rs17841327) were associated with latent class membership for fatigue. Seven genetic associations (i.e., NOS1 rs471871, SLC6A1 rs2675163, SLC6A1 Haplotype D01, SLC6A2 rs36027, SLC6A3 rs37022, SLC6A4 rs2020942, and TAC1 rs2072100) were associated with latent class membership for energy. Only two (i.e., NOS1, SLC6A2) of thirteen genes were associated with latent class membership for both fatigue and

energy.

Conclusions: The molecular findings from this study help support the hypothesis that fatigue and energy are different, yet related symptoms. This study suggests a large number of neurotransmitters (i.e., proteins and receptors) play a role in the development and maintenance of fatigue and energy levels in breast cancer patients.