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 PARTICIPANTSIn 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. RESULTSIn 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, ). 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.

Banana cultivars of agronomic interest have been genetically characterized using two different molecular markers. On the one hand, a panel of 14 trinucleotide single sequence repeats (SSRs or microsatellites) was optimized for homogeneous PCR conditions. It was tested with 50 individuals from seven cultivars, yielding 76 alleles and 5.4 ± 1.8 alleles per locus, while the presence of cultivar-exclusive alleles allowed the discrimination of all cultivars. On the other hand, a retrotransposon-based marker system named inter-primer binding site (iPBS) was implemented for the first time in the Musa genus. A total of 120 bands were detected in eight different Musa cultivars, from which 65.8% were polymorphic and 23.3% were cultivar exclusive. Both techniques allowed a cut-off identification of all cultivars studied, but overall, iPBS analysis was a more straightforward and economical choice. Despite the fact that we were unable to distinguish local banana varieties belonging to the same cultivar, new cultivar-specific molecular markers have been developed for the Musa genus, which could be used to guide new breeding programmes and maintain high quality of Plátano de Canarias.

Around 50% of the familial breast cancer (BC) cases are estimated to be caused by germline variants in known low-, moderate-, and high-risk susceptibility genes, while the other half is of unknown genetic origin. In the present study, we wanted to evaluate the role of the RECQ helicases, some of which have been studied in the past as candidates, with unclear results about their role in the disease. Using next-generation sequencing (NGS) technology, we analyzed the whole coding sequence of BLM, RECQL1, RECQL4, RECQL5, and WRN in almost 2000 index cases from BC Spanish families that had previously tested negative for the known BC susceptibility genes (BRCAX) and compared the results with the controls extracted from gnomAD. Our results suggest that BLM, RECQL1, RECQL4, and WRN do not play a major role in BC susceptibility. However, in the combined analysis, joining the present results with those previously reported in a series of 1334 BC Spanish patients and controls, we found a statistically significant association between Loss of Function (LoF) variants in RECQL5 and BC risk, with an OR of 2.56 (p = 0.009; 95% CI, 1.18–4.98). Our findings support our previous work and places the RECQL5 gene as a new moderate-risk BC gene.