A genome-wide association study of chemotherapy-induced alopecia in breast cancer patients

Suyoun Chung, Siew Kee Low, Hitoshi Zembutsu, Atsushi Takahashi, Michiaki Kubo, Mitsunori Sasa, Yusuke Nakamura

Research output: Contribution to journalArticle

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Abstract

Introduction: Chemotherapy-induced alopecia is one of the most common adverse events caused by conventional cytotoxic chemotherapy, yet there has been very little progress in the prevention or treatment of this side effect. Although this is not a life-threatening event, alopecia is very psychologically difficult for many women to manage. In order to improve the quality of life for these women, it is important to elucidate the molecular mechanisms of chemotherapy-induced alopecia and develop ways to effectively prevent and/or treat it. To identify the genetic risk factors associated with chemotherapy-induced alopecia, we conducted a genome-wide association study (GWAS) using DNA samples from breast cancer patients who were treated with chemotherapy.Methods: We performed a case-control association study of 303 individuals who developed grade 2 alopecia, and compared them with 880 breast cancer patients who did not show hair loss after being treated with conventional chemotherapy. In addition, we separately analyzed a subset of patients who received specific combination therapies by GWASs and applied the weighted genetic risk scoring (wGRS) system to investigate the cumulative effects of the associated SNPs.Results: We identified an SNP significantly associated with drug-induced grade 2 alopecia (rs3820706 in CACNB4 (calcium channel voltage-dependent subunit beta 4) on 2q23, P = 8.13 × 10-9, OR = 3.71) and detected several SNPs that showed some suggestive associations by subgroup analyses. We also classified patients into four groups on the basis of wGRS analysis and found that patients who classified in the highest risk group showed 443 times higher risk of antimicrotubule agents-induced alopecia than the lowest risk group.Conclusions: Our study suggests several associated genes and should shed some light on the molecular mechanism of alopecia in chemotherapy-treated breast cancer patients and hopefully will contribute to development of interventions that will improve the quality of life (QOL) of cancer patients.

Original languageEnglish
Article numberR81
JournalBreast Cancer Research
Volume15
Issue number5
DOIs
Publication statusPublished - 11-09-2013

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Genome-Wide Association Study
Alopecia
Breast Neoplasms
Drug Therapy
Single Nucleotide Polymorphism
Quality of Life
Calcium Channels
Case-Control Studies
DNA
Therapeutics

All Science Journal Classification (ASJC) codes

  • Oncology
  • Cancer Research

Cite this

Chung, S., Low, S. K., Zembutsu, H., Takahashi, A., Kubo, M., Sasa, M., & Nakamura, Y. (2013). A genome-wide association study of chemotherapy-induced alopecia in breast cancer patients. Breast Cancer Research, 15(5), [R81]. https://doi.org/10.1186/bcr3475
Chung, Suyoun ; Low, Siew Kee ; Zembutsu, Hitoshi ; Takahashi, Atsushi ; Kubo, Michiaki ; Sasa, Mitsunori ; Nakamura, Yusuke. / A genome-wide association study of chemotherapy-induced alopecia in breast cancer patients. In: Breast Cancer Research. 2013 ; Vol. 15, No. 5.
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A genome-wide association study of chemotherapy-induced alopecia in breast cancer patients. / Chung, Suyoun; Low, Siew Kee; Zembutsu, Hitoshi; Takahashi, Atsushi; Kubo, Michiaki; Sasa, Mitsunori; Nakamura, Yusuke.

In: Breast Cancer Research, Vol. 15, No. 5, R81, 11.09.2013.

Research output: Contribution to journalArticle

TY - JOUR

T1 - A genome-wide association study of chemotherapy-induced alopecia in breast cancer patients

AU - Chung, Suyoun

AU - Low, Siew Kee

AU - Zembutsu, Hitoshi

AU - Takahashi, Atsushi

AU - Kubo, Michiaki

AU - Sasa, Mitsunori

AU - Nakamura, Yusuke

PY - 2013/9/11

Y1 - 2013/9/11

N2 - Introduction: Chemotherapy-induced alopecia is one of the most common adverse events caused by conventional cytotoxic chemotherapy, yet there has been very little progress in the prevention or treatment of this side effect. Although this is not a life-threatening event, alopecia is very psychologically difficult for many women to manage. In order to improve the quality of life for these women, it is important to elucidate the molecular mechanisms of chemotherapy-induced alopecia and develop ways to effectively prevent and/or treat it. To identify the genetic risk factors associated with chemotherapy-induced alopecia, we conducted a genome-wide association study (GWAS) using DNA samples from breast cancer patients who were treated with chemotherapy.Methods: We performed a case-control association study of 303 individuals who developed grade 2 alopecia, and compared them with 880 breast cancer patients who did not show hair loss after being treated with conventional chemotherapy. In addition, we separately analyzed a subset of patients who received specific combination therapies by GWASs and applied the weighted genetic risk scoring (wGRS) system to investigate the cumulative effects of the associated SNPs.Results: We identified an SNP significantly associated with drug-induced grade 2 alopecia (rs3820706 in CACNB4 (calcium channel voltage-dependent subunit beta 4) on 2q23, P = 8.13 × 10-9, OR = 3.71) and detected several SNPs that showed some suggestive associations by subgroup analyses. We also classified patients into four groups on the basis of wGRS analysis and found that patients who classified in the highest risk group showed 443 times higher risk of antimicrotubule agents-induced alopecia than the lowest risk group.Conclusions: Our study suggests several associated genes and should shed some light on the molecular mechanism of alopecia in chemotherapy-treated breast cancer patients and hopefully will contribute to development of interventions that will improve the quality of life (QOL) of cancer patients.

AB - Introduction: Chemotherapy-induced alopecia is one of the most common adverse events caused by conventional cytotoxic chemotherapy, yet there has been very little progress in the prevention or treatment of this side effect. Although this is not a life-threatening event, alopecia is very psychologically difficult for many women to manage. In order to improve the quality of life for these women, it is important to elucidate the molecular mechanisms of chemotherapy-induced alopecia and develop ways to effectively prevent and/or treat it. To identify the genetic risk factors associated with chemotherapy-induced alopecia, we conducted a genome-wide association study (GWAS) using DNA samples from breast cancer patients who were treated with chemotherapy.Methods: We performed a case-control association study of 303 individuals who developed grade 2 alopecia, and compared them with 880 breast cancer patients who did not show hair loss after being treated with conventional chemotherapy. In addition, we separately analyzed a subset of patients who received specific combination therapies by GWASs and applied the weighted genetic risk scoring (wGRS) system to investigate the cumulative effects of the associated SNPs.Results: We identified an SNP significantly associated with drug-induced grade 2 alopecia (rs3820706 in CACNB4 (calcium channel voltage-dependent subunit beta 4) on 2q23, P = 8.13 × 10-9, OR = 3.71) and detected several SNPs that showed some suggestive associations by subgroup analyses. We also classified patients into four groups on the basis of wGRS analysis and found that patients who classified in the highest risk group showed 443 times higher risk of antimicrotubule agents-induced alopecia than the lowest risk group.Conclusions: Our study suggests several associated genes and should shed some light on the molecular mechanism of alopecia in chemotherapy-treated breast cancer patients and hopefully will contribute to development of interventions that will improve the quality of life (QOL) of cancer patients.

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