Chung Suyoun, Low Siew-Kee, Zembutsu Hitoshi, Takahashi Atsushi, Kubo Michiaki, Sasa Mitsunori, Nakamura Yusuke
Breast Cancer Res. 2013;15(5):R81. doi: 10.1186/bcr3475.
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.
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.
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.
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.
化疗引起的脱发是传统细胞毒性化疗最常见的不良事件之一，但在预防或治疗这种副作用方面进展甚微。虽然这并非危及生命的事件，但脱发对许多女性来说在心理上很难应对。为了提高这些女性的生活质量，阐明化疗引起脱发的分子机制并开发有效预防和/或治疗方法很重要。为了确定与化疗引起脱发相关的遗传风险因素，我们使用接受化疗的乳腺癌患者的DNA样本进行了全基因组关联研究（GWAS）。
我们对303例出现2级脱发的个体进行了病例对照关联研究，并将他们与880例接受传统化疗后未出现脱发的乳腺癌患者进行比较。此外，我们通过GWAS分别分析了接受特定联合治疗的患者亚组，并应用加权遗传风险评分（wGRS）系统来研究相关单核苷酸多态性（SNP）的累积效应。
我们鉴定出一个与药物引起的2级脱发显著相关的SNP（位于2q23的CACNB4（钙通道电压依赖性亚基β4）中的rs3820706，P = 8.13×10⁻⁹，比值比（OR） = 3.71），并通过亚组分析检测到几个显示出一些提示性关联的SNP。我们还根据wGRS分析将患者分为四组，发现分类为最高风险组的患者发生抗微管药物引起脱发的风险比最低风险组高443倍。
我们的研究提示了几个相关基因，应该有助于阐明化疗治疗的乳腺癌患者脱发的分子机制，有望为改善癌症患者生活质量（QOL）的干预措施的开发做出贡献。
