UCSF

Background - This study sought to replicate the findings from our previous candidate gene analyses of pro- and anti-inflammatory cytokines in a sample of patients who were assessed prior to and for six months following breast cancer surgery. Specifically phenotypic differences between the Resilient (n=155) and Subsyndromal (n=180) depressive symptom classes were evaluated as well as variations in cytokine genes between the two latent classes.

Methods - Among 398 breast cancer patients following surgery, growth mixture modeling was used to identify latent classes based on Center for Epidemiological Studies Depression (CES-D) Scale scores. The CES-D was completed prior to surgery and monthly for a total of six months following breast cancer surgery. A total of 103 single nucleotide polymorphisms and 35 haplotypes among 15 candidate cytokine genes were included in the genetic association analyses.

Results - Patients in the Subsyndromal class were significantly younger, more likely to be married or partnered, and reported a significantly lower KPS score than patients in the Resilient class. Variation in three cytokine genes (i.e., tumor necrosis factor alpha (TNFA), interferon gamma receptor 1 (IFNGR1), interleukin 6 (IL6)), as well as age and functional status predicted membership in the Subsyndromal versus the Resilient class.

Conclusion - Growth mixture modeling identified two distinct groups of patients who differ in their experience with depressive symptoms. Variations in cytokine genes may influence the trajectory of depressive symptoms in high risk patients.