Retrospective analysis of The Two Sister Study using haplotype-based association testing to identify loci associated with early-onset breast cancer
Gilbert, J. R.; Cray, J. J.; Losee, J. E.; Cooper, G. M.
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Breast cancer is a polygenic disorder and is the leading cause of cancer related mortality among women. Early-onset breast cancer (EOBC) is diagnosed in women prior to 45 years-of-age and is associated with worse clinical outcomes, a more aggressive disease phenotype, and poor prognosis for disease-free survival. While substantial progress has been made in defining the genetics of breast cancer, EOBC remains less well understood. In the current study we perform a retrospective analysis of data derived from The Two Sister Study. The use of alternate strategies for handling age-at-diagnosis in conjunction with haplotype-based methods yielded novel findings that help to explain the heritability of EOBC. These findings are validated through comparison against discordant sibs from The Two Sister Study as well as using data derived The Cancer Genome Atlas (TCGA).
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