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Träfflista för sökning "WFRF:(dos Santos Silva Isabel) srt2:(2010-2014);srt2:(2013)"

Sökning: WFRF:(dos Santos Silva Isabel) > (2010-2014) > (2013)

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  • Meyer, Kerstin B., et al. (författare)
  • Fine-Scale Mapping of the FGFR2 Breast Cancer Risk Locus: Putative Functional Variants Differentially Bind FOXA1 and E2F1
  • 2013
  • Ingår i: American Journal of Human Genetics. - : Cell Press. - 0002-9297 .- 1537-6605. ; 93:6, s. 1046-1060
  • Tidskriftsartikel (refereegranskat)abstract
    • The 10q26 locus in the second intron of FGFR2 is the locus most strongly associated with estrogen-receptor-positive breast cancer in genome-wide association studies. We conducted fine-scale mapping in case-control studies genotyped with a custom chip (iCOGS), comprising 41 studies (n = 89,050) of European ancestry, 9 Asian ancestry studies (n = 13,983), and 2 African ancestry studies (n = 2,028) from the Breast Cancer Association Consortium. We identified three statistically independent risk signals within the locus. Within risk signals 1 and 3, genetic analysis identified five and two variants, respectively, highly correlated with the most strongly associated SNPs. By using a combination of genetic fine mapping, data on DNase hypersensitivity, and electrophoretic mobility shift assays to study protein-DNA binding, we identified rs35054928, rs2981578, and rs45631563 as putative functional SNPs. Chromatin immunoprecipitation showed that FOXA1 preferentially bound to the risk-associated allele (C) of rs2981578 and was able to recruit ER alpha to this site in an allele-specific manner, whereas E2F1 preferentially bound the risk variant of rs35054928. The risk alleles were preferentially found in open chromatin and bound by Ser5 phosphorylated RNA polymerase II, suggesting that the risk alleles are associated with changes in transcription. Chromatin conformation capture demonstrated that the risk region was able to interact with the promoter of FGFR2, the likely target gene of this risk region. A role for FOXA1 in mediating breast cancer susceptibility at this locus is consistent with the finding that the FGFR2 risk locus primarily predisposes to estrogen-receptor-positive disease.
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  • Sovio, Ulla, et al. (författare)
  • Birth size and survival in breast cancer patients from the Uppsala Birth Cohort Study
  • 2013
  • Ingår i: Cancer Causes and Control. - 0957-5243 .- 1573-7225. ; 24:9, s. 1643-1651
  • Tidskriftsartikel (refereegranskat)abstract
    • PurposePrevious studies suggest that larger birth size is associated with a higher breast cancer incidence, but studies on birth measures and mortality in breast cancer cases are scarce. This study investigates survival of women after breast cancer diagnosis (n = 437) in the Uppsala Birth Cohort born in 1915–1929.MethodsCox regression was used to analyze mortality from any cause after a breast cancer diagnosis. Birth measures including gestational age (GA), birth weight (BW), BW for GA, birth length, and ponderal index (PI) were converted to standard deviation (SD) scores, and all analyses were adjusted for age and calendar time at diagnosis. Analyses were performed with and without adjustment for other birth measures, reproductive history, and adult socioeconomic position.ResultsIn fully adjusted analyses, one SD increase in GA was associated with 17 % [95 % confidence interval (CI) 6–26 %] lower mortality and one SD increase in BW was associated with 29 % (7–56 %) higher mortality. PI showed a weaker trend in the same direction: hazard ratio = 1.16 (95 % CI 1.03–1.30).ConclusionsOur results bring in new evidence that both high GA and low BW predict a better survival in breast cancer cases. Further studies need to investigate mediation of these associations.
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