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

doi:10.1007/s10549-014-2832-y

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

Department of Nursing

Research output: Contribution to journal › Article › peer-review

Abstract

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.

Original language	English
Pages (from-to)	123-131
Number of pages	9
Journal	Breast Cancer Research and Treatment
Volume	144
Issue number	1
DOIs	https://doi.org/10.1007/s10549-014-2832-y
State	Published - Feb 2014

Bibliographical note

Funding Information:
Acknowledgments This work was financially supported by the Israel Cancer Association; The Cancer Biology Research Center, Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel; and TASMC excellence fund. The assistance of Mrs. Tami Modiano, Mrs. Yael Golan-Vered, and Mrs. Batia Granit in recruiting the patients and running the study is greatly appreciated.

Keywords

Breast cancer
Chemotherapy
Genetics
HTR3C
Symptoms

ASJC Scopus subject areas

Oncology
Cancer Research

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1007/s10549-014-2832-y

Cite this

Pud, D., Har-Zahav, G., Laitman, Y., Rubinek, T., Yeheskel, A., Ben-Ami, S., Kaufman, B., Friedman, E., Symon, Z., & Wolf, I. (2014). Association between variants of 5-hydroxytryptamine receptor 3C (HTR3C) and chemotherapy-induced symptoms in women receiving adjuvant treatment for breast cancer. Breast Cancer Research and Treatment, 144(1), 123-131. https://doi.org/10.1007/s10549-014-2832-y

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abstract = "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.",

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note = "Funding Information: Acknowledgments This work was financially supported by the Israel Cancer Association; The Cancer Biology Research Center, Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel; and TASMC excellence fund. The assistance of Mrs. Tami Modiano, Mrs. Yael Golan-Vered, and Mrs. Batia Granit in recruiting the patients and running the study is greatly appreciated.",

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Pud, D, Har-Zahav, G, Laitman, Y, Rubinek, T, Yeheskel, A, Ben-Ami, S, Kaufman, B, Friedman, E, Symon, Z & Wolf, I 2014, 'Association between variants of 5-hydroxytryptamine receptor 3C (HTR3C) and chemotherapy-induced symptoms in women receiving adjuvant treatment for breast cancer', Breast Cancer Research and Treatment, vol. 144, no. 1, pp. 123-131. https://doi.org/10.1007/s10549-014-2832-y

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T1 - Association between variants of 5-hydroxytryptamine receptor 3C (HTR3C) and chemotherapy-induced symptoms in women receiving adjuvant treatment for breast cancer

AU - Pud, Dorit

AU - Har-Zahav, Gil

AU - Laitman, Yael

AU - Rubinek, Tami

AU - Yeheskel, Adva

AU - Ben-Ami, Sarah

AU - Kaufman, Bella

AU - Friedman, Eitan

AU - Symon, Zvi

AU - Wolf, Ido

N1 - Funding Information: Acknowledgments This work was financially supported by the Israel Cancer Association; The Cancer Biology Research Center, Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel; and TASMC excellence fund. The assistance of Mrs. Tami Modiano, Mrs. Yael Golan-Vered, and Mrs. Batia Granit in recruiting the patients and running the study is greatly appreciated.

PY - 2014/2

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N2 - 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.

AB - 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.

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

Abstract

Bibliographical note

Keywords

ASJC Scopus subject areas

UN SDGs

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