Breast Cancer Research and Treatment

, Volume 144, Issue 1, pp 123–131

Association between variants of 5-hydroxytryptamine receptor 3C (HTR3C) and chemotherapy-induced symptoms in women receiving adjuvant treatment for breast cancer

  • Dorit Pud
  • Gil Har-Zahav
  • Yael Laitman
  • Tami Rubinek
  • Adva Yeheskel
  • Sarah Ben-Ami
  • Bella Kaufman
  • Eitan Friedman
  • Zvi Symon
  • Ido Wolf
Clinical Trial


Administration of chemotherapy is associated with a wide array of symptoms affecting quality of life. Genetic risk factors for severity of chemotherapy-induced symptoms have not been determined. The present study aimed to explore the associations between polymorphisms in candidate genes and chemotherapy-induced symptoms. Women treated with at least two cycles of adjuvant doxorubicin and cyclophosphamide, with or without paclitaxel for early breast cancer (n = 105) completed the memorial symptom assessment scale and provided blood for genotyping. DNA was extracted from peripheral blood leukocytes and assayed for single nucleotide polymorphisms (SNPs) in GTP cyclohydrolase 1 (GCH1, rs10483639, rs3783641, and rs8007267), catecholamine-o-methyltransferase (COMT, rs4818), and 5-hydroxytryptamine (serotonin) receptor 3C (HTR3C, rs6766410, and rs6807362). Genotyping of HTR3C revealed a significant association between the presence of rs6766410 and rs6807362 SNPs (K163 and G405 variants) and increased severity of symptoms (p = 0.0001 and p = 0.007, respectively). Multiple regressions revealed that rs6766410 and rs6807362, but not age or stage at diagnosis, predicted severity of symptoms (p = 0.001 and p = 0.006, respectively) and explained 12 % of the variance in each regression model. No association was found between the genetic variants of CGH1 or COMT and symptom score. Our study indicates, for the first time, an association between variants of HTR3C and severity of chemotherapy-induced symptoms. Analyzing these genetic variants may identify patients at increased risk for the development of chemotherapy-induced symptoms and targeting the serotonin pathway may serve as a novel treatment strategy for these patients.


Chemotherapy Symptoms Genetics HTR3C Breast cancer 


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Copyright information

© Springer Science+Business Media New York 2014

Authors and Affiliations

  • Dorit Pud
    • 1
  • Gil Har-Zahav
    • 2
  • Yael Laitman
    • 3
  • Tami Rubinek
    • 4
  • Adva Yeheskel
    • 5
  • Sarah Ben-Ami
    • 6
  • Bella Kaufman
    • 6
    • 7
  • Eitan Friedman
    • 3
    • 7
  • Zvi Symon
    • 6
    • 7
  • Ido Wolf
    • 4
    • 7
  1. 1.Faculty of Social Welfare and Health SciencesUniversity of HaifaHaifaIsrael
  2. 2.Department of Surgery BChaim Sheba Medical CenterRamat-GanIsrael
  3. 3.Susanne Levy Gertner Oncogenetics UnitChaim Sheba Medical CenterRamat-GanIsrael
  4. 4.Institute of OncologyTel Aviv Sourasky Medical CenterTel AvivIsrael
  5. 5.The Bioinformatics Unit, George S. Wise Faculty of Life SciencesTel Aviv UniversityTel AvivIsrael
  6. 6.Oncology InstituteChaim Sheba Medical CenterRamat-GanIsrael
  7. 7.Sackler Faculty of MedicineTel Aviv UniversityTel AvivIsrael

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