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Brief Report
August 5, 2020

Association Between ABCB1 Genetic Variants and Persistent Chemotherapy-Induced Alopecia in Women With Breast Cancer

Author Affiliations
  • 1Human Genotyping Unit–CeGen (Spanish National Genotyping Centre), Human Cancer Genetics Programme, Spanish National Cancer Research Centre (CNIO), Madrid, Spain
  • 2Medical Oncology Department, Hospital Universitario Gregorio Marañón, Departamento de Medicina, Universidad Complutense CiberOnC, Madrid, Spain
  • 3Hospital Clínico San Carlos, Medical Oncology Department, Instituto de Investigación Sanitaria del Hospital Clínico San Carlos, CIBERONC, Madrid, Spain
  • 4Universidad Pontificia Comillas, Madrid, Spain
  • 5Hematology and Oncology Department, Hospital Clínico Universitario, Valencia, Spain
  • 6INCLIVA Biobank, INCLIVA Biomedical Research Institute, Valencia, Spain
  • 7INCLIVA Biomedical Research Institute, Valencia, Spain
  • 8University of Valencia, Spain
  • 9Centro de Investigación Biomédica en Red de Oncología, CIBERONC-ISCIII
JAMA Dermatol. 2020;156(9):987-991. doi:10.1001/jamadermatol.2020.1867
Key Points

Question  Does an association exist between genetic factors and the development of persistent chemotherapy-induced alopecia?

Findings  This agnostic genome-wide association study of 215 women with breast cancer treated with docetaxel-based therapies found genetic variants in the ABCB1 gene that were significantly associated with the risk to develop persistent chemotherapy-induced alopecia. This finding was replicated in an independent cohort.

Meaning  To our knowledge, this is the first report suggesting an association between genetic variants and the risk to develop persistent chemotherapy-induced alopecia.


Importance  Persistent chemotherapy-induced alopecia (pCIA) has been recently described in patients with breast cancer and in its most severe form occurs in up to 10% of these patients. Genetic risk factors associated with pCIA have not been adequately explored.

Objective  To identify genetic variants associated with pCIA.

Design, Setting, and Participants  In this genetic association study, 215 women with breast cancer treated with docetaxel-based chemotherapy with a follow-up of 1.5 to 10 years after the end of the treatment were recruited retrospectively through 3 hospital oncology units across Spain between 2005 and 2018. Severe pCIA was defined as lack of scalp hair recovery (Common Terminology Criteria for Adverse Events, version 3.0, grade 2) 18 months or more after the end of treatment. Patients with grade 2 pCIA were selected as cases, and those with no sign of residual alopecia 12 months after the end of docetaxel treatment were selected as controls. A genome-wide association study in a discovery phase was conducted, and logistic regression was used to identify variants associated with the risk to develop this adverse effect. The validity of the association was addressed through a replication phase.

Exposures  Docetaxel-based chemotherapy.

Main Outcomes and Measures  Genotypes of single-nucleotide variants associated with pCIA.

Results  In total, 215 women with breast cancer (median age, 51.6 years; interquartile range, 44-60 years) were recruited (173 patients for the discovery phase and 42 patients for the replication phase). In the discovery phase, ABCB1 genetic variants were associated with risk to develop pCIA. In particular, single-nucleotide variation rs1202179, a regulatory variant located in an enhancer element that interacts with the ABCB1 promoter, was associated with the occurrence of pCIA. This finding was validated in the replication cohort (combined odds ratio, 4.05; 95% CI, 2.46-6.67; P = 3.946 × 10−8). This variant is associated with ABCB1 mRNA expression, and the risk allele was associated with decreased ABCB1 expression levels (P = 1.64 × 10−20).

Conclusions and Relevance  This is the first study, to our knowledge, that identifies an association between a regulatory variant in the ABCB1 gene and the occurrence of pCIA in patients with breast cancer who were treated with docetaxel-based therapies. This finding suggests an important insight into the biological mechanisms underlying pCIA and opens the opportunity to explore personalized treatment of these patients.

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