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

被引:25
作者
Chung, Suyoun [1 ,6 ]
Low, Siew-Kee [3 ,6 ]
Zembutsu, Hitoshi [6 ]
Takahashi, Atsushi [3 ]
Kubo, Michiaki [4 ]
Sasa, Mitsunori [5 ]
Nakamura, Yusuke [1 ,2 ,6 ]
机构
[1] Univ Chicago, Dept Med, Chicago, IL 60637 USA
[2] Univ Chicago, Dept Surg, Chicago, IL 60637 USA
[3] Ctr Genom Med, Lab Stat Anal, Tsurumi Ku, Yokohama, Kanagawa 2300045, Japan
[4] Ctr Genom Med, Lab Genotyping Dev, Yokohama, Kanagawa 2300045, Japan
[5] Tokushima Breast Care Clin, Tokushima 7700052, Japan
[6] Univ Tokyo, Ctr Human Genome, Inst Med Sci, Lab Genotyping Dev,Minato Ku, Tokyo 1088639, Japan
来源
BREAST CANCER RESEARCH | 2013年 / 15卷 / 05期
关键词
HAIR LOSS; MINOXIDIL; EPIDERMIS; STAM2; WOMEN;
D O I
10.1186/bcr3475
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
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 x 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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页数:10
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