International journal of cancer. Journal international du cancer
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Every cancer-related death in someone of working age represents an economic loss to society. To inform priorities for cancer control, we estimated costs of lost productivity due to premature cancer-related mortality across Europe, for all cancers and by site, gender, region and country. Cancer deaths in 2008 were obtained from GLOBOCAN for 30 European countries across four regions. ⋯ Premature mortality costs were 0.58% of 2008 European gross domestic product, highest in Central-Eastern Europe (0.81%) and lowest in Northern Europe (0.51%). Premature cancer-related mortality costs in Europe are significant. These results provide a novel perspective on the societal cancer burden and may be used to inform priority setting for cancer control.
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We investigated the clinical relevance of dihydropyrimidine dehydrogenase gene (DPYD) variants to predict severe early-onset fluoropyrimidine (FP) toxicity, in particular of a recently discovered haplotype hapB3 and a linked deep intronic splice site mutation c.1129-5923C>G. Selected regions of DPYD were sequenced in prospectively collected germline DNA of 500 patients receiving FP-based chemotherapy. Associations of DPYD variants and haplotypes with hematologic, gastrointestinal, infectious, and dermatologic toxicity in therapy cycles 1-2 and resulting FP-dose interventions (dose reduction, therapy delay or cessation) were analyzed accounting for clinical and demographic covariates. ⋯ The c.1129-5923C>G/hapB3 variant is a major contributor to severe early-onset FP toxicity in Caucasian patients. This variant may substantially improve the identification of patients at risk of FP toxicity compared to established DPYD risk variants (c.1905+1G>A, c.1679T>G and c.2846A>T). Pre-therapeutic DPYD testing may prevent 20-30% of life-threatening or lethal episodes of FP toxicity in Caucasian patients.