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

• Published in: Breast cancer research and treatment 2014-02, Vol.144 (1), p.123-131
• Main Authors: Pud, Dorit, Har-Zahav, Gil, Laitman, Yael, Rubinek, Tami, Yeheskel, Adva, Ben-Ami, Sarah, Kaufman, Bella, Friedman, Eitan, Symon, Zvi, Wolf, Ido
• Format: Article
• Language: English
• Subjects: Adjuvant treatment; Adult; Aged; Anthracyclines; Antineoplastic Combined Chemotherapy Protocols - adverse effects; Breast cancer; Breast Neoplasms - drug therapy; Breast Neoplasms - genetics; Cancer; Cancer research; Cancer therapies; Care and treatment; Chemotherapy; Chemotherapy, Adjuvant - adverse effects; Chromosomes; Clinical outcomes; Clinical Trial; Clinical trials; Cyclophosphamide - administration & dosage; Cyclophosphamide - adverse effects; DNA; Doxorubicin - administration & dosage; Doxorubicin - adverse effects; Female; Genetic Predisposition to Disease; Genotype; Genotype & phenotype; Humans; Medicine; Medicine & Public Health; Middle Aged; Oncology; Paclitaxel - administration & dosage; Paclitaxel - adverse effects; Polymorphism, Restriction Fragment Length; Polymorphism, Single Nucleotide; Receptors, Serotonin, 5-HT3 - genetics; Risk factors; Single nucleotide polymorphisms; Women; Young Adult
• ISSN: 0167-6806; 1573-7217
• DOI: 10.1007/s10549-014-2832-y

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.