Women treated at young ages with supradiaphragmatic radiotherapy for Hodgkin lymphoma (HL) have a highly increased risk of breast cancer. For personalised advice and follow-up regimens for patients, information is needed on how the radiotherapy-related risk is affected by other breast cancer risk factors. Genome-wide association studies have identified 14 independently replicated common single nucleotide polymorphisms (SNPs) that influence breast cancer risk. To examine whether these variants contribute to risk of radiation-associated breast cancer in HL we analysed two independent case-control series, from the UK and Netherlands, totalling 693 HL patients, 232 with breast cancer and 461 without. rs1219648, which annotates the FGFR2 gene, was associated with risk in both series (combined per-allele odds ratio =1.59, 95% confidence interval: 1.26-2.02; P=1.11x10(-4)). These data provide evidence that genetic variation in FGFR2 influences radiation-induced breast cancer risk.
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