Cytokine gene variations associated with subsyndromal depressive symptoms in patients with breast cancer

Abstract

Purpose This study explored the relationships between variations in cytokines genes and depressive symptoms in a sample of patients who were assessed prior to and for six months following breast cancer surgery. Phenotypic differences between Resilient (n=155) and Subsyndromal (n=180) depressive symptom classes, as well as variations in cytokine genes were evaluated. Method Patients were recruited prior to surgery and followed for six months. Growth mixture modeling was used to identify distinct latent classes based on Center for Epidemiological Studies Depression (CES-D) Scale scores. Eighty-two single nucleotide polymorphisms and 35 haplotypes among 15 candidate cytokine genes were evaluated. Results Patients in the Subsyndromal class were significantly younger, more likely to be married or partnered, and reported a significantly lower functional status. Variation in three cytokine genes (i.e., interferon gamma receptor 1 (IFNGR1 rs9376268), interleukin 6 (IL6 rs2069840), tumor necrosis factor alpha (TNFA rs1799964)), as well as age and functional status predicted membership in the Subsyndromal versus the Resilient class. Conclusions A variation in TNFA that was associated with Subsyndromal depressive symptoms in a sample of patients and their family caregivers was confirmed in this sample. Variations in cytokine genes may place these patients at higher risk for the development of Subsyndromal levels of depressive symptoms.

Genetic polymorphisms associated with common symptoms experienced by breast cancer patients

“…Consistent with the findings of Saad et al on the association between TNF-α (rs1799964) and the development of subsyndromal depression [75], a corresponding decreased odds of higher anxiety class was also observed with the SNP (rs1799964) among breast cancer patients undergoing breast surgery [82]. On the other hand, this study also observed that TNF-α (rs3093662) was associated with higher odds of developing anxiety therefore suggesting that TNF-α SNPs may serve as important predictive marker of increased susceptibility to psychological distress among breast cancer patients.…”

“…The study also demonstrated that SNPs in Interferon Gamma Receptor 1 (IFNGR1, rs9376268) and IL6 (rs2069840) were associated with the development of subsyndromal depressive symptoms. Nevertheless, in contrast to the findings by Kim et al [71] which demonstrated a significant association between IL1B and depression, similar findings could not be confirmed by Saad et al [75]. Furthermore, the associations between SNPs in cytokines and depression appeared to vary depending on the cancer type; for instance, Duun et al [76] reported an association between two TNF-α SNPs (rs2229074, rs1800629) and depression in patients with various types of cancer (breast, prostate, lung and brain) and their family care givers.…”

“…Although the IL6 (rs2069845) is reported to be associated with the symptom cluster for the first time in this study, other SNPs in the IL6 have been previously reported to be associated with fatigue [61] and depression [61,75]. For the IL13 (rs1295686), contradictory results exist in a different cohort of oncology patients and their family caregivers [127] where no association was established with the symptom cluster.…”

“…Furthermore, the associations between SNPs in cytokines and depression appeared to vary depending on the cancer type; for instance, Duun et al [76] reported an association between two TNF-α SNPs (rs2229074, rs1800629) and depression in patients with various types of cancer (breast, prostate, lung and brain) and their family care givers. On the contrary, similar association was not demonstrable in a cohort of breast cancer patients [71,75]. Owing to the complex nature of cancer related depression with multiple genetic factors implicated, additional larger multi-centre studies involving different ethnicities and targeting multiple SNPs may reveal the actual combined effects of the genes [71].…”

“…Another similar study [75] reported that breast cancer patients who were homozygous for a rare allele variant of TNF-α (rs1799964) had lower odds of developing subsyndromal depression. The study also demonstrated that SNPs in Interferon Gamma Receptor 1 (IFNGR1, rs9376268) and IL6 (rs2069840) were associated with the development of subsyndromal depressive symptoms.…”