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• W2079671151 abstract "Therapy-related acute myeloid leukemia (t-AML) is a rare but fatal complication of cytotoxic therapy. Whereas sporadic cancer results from interactions between complex exposures and low-penetrance alleles, t-AML results from an acute exposure to a limited number of potent genotoxins. Consequently, we hypothesized that the effect sizes of variants associated with t-AML would be greater than in sporadic cancer, and, therefore, that these variants could be detected even in a modest-sized cohort. To test this, we undertook an association study in 80 cases and 150 controls using Affymetrix Mapping 10K arrays. Even at nominal significance thresholds, we found a significant excess of associations over chance; for example, although 6 associations were expected at P less than .001, we found 15 (P(enrich) = .002). To replicate our findings, we genotyped the 10 most significantly associated single nucleotide polymorphisms (SNPs) in an independent t-AML cohort (n = 70) and obtained evidence of association with t-AML for 3 SNPs in the subset of patients with loss of chromosomes 5 or 7 or both, acquired abnormalities associated with prior exposure to alkylator chemotherapy. Thus, we conclude that the effect of genetic factors contributing to cancer risk is potentiated and more readily discernable in t-AML compared with sporadic cancer." @default.
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• W2079671151 date "2009-05-28" @default.
• W2079671151 modified "2023-10-06" @default.
• W2079671151 title "Genome-wide association study to identify novel loci associated with therapy-related myeloid leukemia susceptibility" @default.
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• W2079671151 doi "https://doi.org/10.1182/blood-2008-10-183244" @default.
• W2079671151 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/2689055" @default.
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