title: Genetic risk score and acute skin toxicity after breast radiation therapy.
abstract: Genetic predisposition has been shown to affect the severity of skin complications in breast cancer patients after radiotherapy. Limited data exist regarding the use of a genetic risk score (GRS) for predicting risk of tissue radiosensitivity. We evaluated the impact of different single-nucleotide polymorphisms (SNPs) in genes related to DNA repair mechanisms and oxidative stress response combined in a GRS on acute adverse effects induced by breast radiation therapy (RT). Skin toxicity was scored according to the Radiation Therapy Oncology Group (RTOG) criteria in 59 breast cancer patients who received RT. After genotyping, a multilocus GRS was constructed by summing the number of risk alleles. The hazard ratio (HR) for GSTM1 was 2.4 (95% confidence intervals [CI]=1.1-5.3, p=0.04). The other polymorphisms were associated to an increased adverse radiosensitivity, although they did not reach statistical significance. GRS predicted roughly 40% risk for acute skin toxicity per risk allele (HR 1.37, 95% CI=1.1-1.76, p<0.01). Patients in the top tertile had a fivefold higher risk of skin reaction (HR 5.1, 95% CI=1.2-22.8, p=0.03). Our findings demonstrate that the joint effect of SNPs from oxidative stress and DNA damage repair genes may be a promising approach to identify patients with a high risk of skin reaction after breast RT.
authors.affiliation: 1 CNR Institute of Clinical Physiology , Pisa, Italy .
authors.forename: Andrea
authors.initials: A
authors.lastname: Borghini
authors.forename: Cecilia
authors.initials: C
authors.lastname: Vecoli
authors.forename: Antonella
authors.initials: A
authors.lastname: Mercuri
authors.forename: Maria Fonte
authors.initials: MF
authors.lastname: Petruzzelli
authors.forename: Maria Patrizia
authors.initials: MP
authors.lastname: D'Errico
authors.forename: Maurizio
authors.initials: M
authors.lastname: Portaluri
authors.forename: Maria Grazia
authors.initials: MG
authors.lastname: Andreassi
mesh_terms: D000483:Alleles; D001943:Breast Neoplasms / Q000235:genetics* / Q000532:radiotherapy*; D004249:DNA Damage / Q000235:genetics / Q000528:radiation effects; D004260:DNA Repair / Q000235:genetics / Q000528:radiation effects; D005260:Female; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D005838:Genotype; D005982:Glutathione Transferase / Q000235:genetics; D006801:Humans; D008875:Middle Aged; D018384:Oxidative Stress / Q000235:genetics / Q000528:radiation effects; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D011836:Radiation Tolerance / Q000235:genetics*; D011878:Radiotherapy / Q000009:adverse effects*; D012306:Risk; D012307:Risk Factors; D012867:Skin / Q000528:radiation effects*
chemical_list: D005982:Glutathione Transferase
keywords: acute skin toxicity; breast radiation therapy; genetic risk score