A one year longitudinal study of cytokine genes and depression in breast cancer

J Affect Disord. 2013 May 15;148(1):57-65. doi: 10.1016/j.jad.2012.11.048. Epub 2012 Dec 29.

Abstract

Background: Since inflammatory cytokines have been implicated in the pathophysiology of both cancer and depression, genes that contribute to determining cytokine functional activity are reasonable candidate risk factors for depression related to cancer. This study aimed to investigate whether alleles related to higher pro-inflammatory and/or lower anti-inflammatory cytokine production would associate with depression in a cohort with breast cancer.

Methods: A total of 309 women with breast cancer were evaluated one week after surgery, and 244 (79%) were followed one year later. Depression (major+minor depressive disorders) was diagnosed according to DSM-IV criteria using the Mini International Neuropsychiatric Interview on both occasions. Six pro-(TNF-α-850C/T and -308G/A, IL-1β-511C/T and +3953C/T, IL-6-174G/C, IL-8-251T/A) and two anti-inflammatory (IL-4 +33T/C, IL-10-1082G/A) cytokine polymorphisms were assayed, and total numbers of potential risk alleles were calculated for pro- and anti-inflammatory cytokine genes. Adjustments were made for demographic and clinical characteristics.

Results: At baseline, 74 (24%) patients were classified with prevalent depression; and at follow-up, 19 (8%) and 25 (10%) patients were classified with persistent and incident depression, respectively. A higher number of pro-inflammatory cytokine risk alleles, and IL-1β-511T/T genotype individually, were independently associated with both prevalent depression at baseline and persistent depression at one year follow-up.

Limitations: Sample size was relatively small.

Conclusions: Our findings support the role of pro-inflammatory cytokines in the etiology of depression related to breast cancer, and provide novel evidence of a potential genetic basis for this.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Breast Neoplasms / psychology*
  • Breast Neoplasms / surgery
  • Cytokines / genetics*
  • Depression / diagnosis*
  • Depression / genetics*
  • Diagnostic and Statistical Manual of Mental Disorders
  • Female
  • Follow-Up Studies
  • Genetic Predisposition to Disease*
  • Humans
  • Interleukin-10 / genetics
  • Interleukin-1beta / genetics
  • Interleukin-4 / genetics
  • Interleukin-6 / genetics
  • Interleukin-8 / genetics
  • Middle Aged
  • Polymorphism, Genetic
  • Risk Factors
  • Time Factors
  • Tumor Necrosis Factor-alpha / genetics

Substances

  • Cytokines
  • Interleukin-1beta
  • Interleukin-6
  • Interleukin-8
  • Tumor Necrosis Factor-alpha
  • Interleukin-10
  • Interleukin-4