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Sökning: WFRF:(Li Jingmei) > (2017)

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1.
  • Michailidou, Kyriaki, et al. (författare)
  • Association analysis identifies 65 new breast cancer risk loci.
  • 2017
  • Ingår i: Nature. - : Nature Publishing Group. - 0028-0836 .- 1476-4687. ; 551:7678, s. 92-94
  • Tidskriftsartikel (refereegranskat)abstract
    • Breast cancer risk is influenced by rare coding variants in susceptibility genes, such as BRCA1, and many common, mostly non-coding variants. However, much of the genetic contribution to breast cancer risk remains unknown. Here we report the results of a genome-wide association study of breast cancer in 122,977 cases and 105,974 controls of European ancestry and 14,068 cases and 13,104 controls of East Asian ancestry. We identified 65 new loci that are associated with overall breast cancer risk at P < 5 × 10-8. The majority of credible risk single-nucleotide polymorphisms in these loci fall in distal regulatory elements, and by integrating in silico data to predict target genes in breast cells at each locus, we demonstrate a strong overlap between candidate target genes and somatic driver genes in breast tumours. We also find that heritability of breast cancer due to all single-nucleotide polymorphisms in regulatory features was 2-5-fold enriched relative to the genome-wide average, with strong enrichment for particular transcription factor binding sites. These results provide further insight into genetic susceptibility to breast cancer and will improve the use of genetic risk scores for individualized screening and prevention.
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  • Ugalde-Morales, Emilio, et al. (författare)
  • Common shared genetic variation behind decreased risk of breast cancer in celiac disease
  • 2017
  • Ingår i: ; 7
  • Tidskriftsartikel (refereegranskat)abstract
    • There is epidemiologic evidence showing that women with celiac disease have reduced risk of later developing breast cancer, however, the etiology of this association is unclear. Here, we assess the extent of genetic overlap between the two diseases. Through analyses of summary statistics on densely genotyped immunogenic regions, we show a significant genetic correlation (r = -0.17, s.e. 0.05, P < 0.001) and overlap (Ppermuted < 0.001) between celiac disease and breast cancer. Using individuallevel genotype data from a Swedish cohort, we find higher genetic susceptibility to celiac disease summarized by polygenic risk scores to be associated with lower breast cancer risk (ORper-SD, 0.94, 95% CI 0.91 to 0.98). Common single nucleotide polymorphisms between the two diseases, with low P-values (P-CD < 1.00E-05, P-BC <= 0.05), mapped onto genes enriched for immunoregulatory and apoptotic processes. Our results suggest that the link between breast cancer and celiac disease is due to a shared polygenic variation of immune related regions, uncovering pathways which might be important for their development.
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4.
  • Yang, Haomin, et al. (författare)
  • Risk and predictors of psoriasis in patients with breast cancer : a Swedish population-based cohort study
  • 2017
  • Ingår i: ; 15:1
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND: The risk of psoriasis in patients with breast cancer is largely unknown, as available evidence is limited to case findings. We systematically examined the incidence and risk factors of psoriasis in patients with breast cancer.METHODS: A Swedish nationwide cohort of 56,235 breast cancer patients (2001-2012) was compared to 280,854 matched reference individuals from the general population to estimate the incidence and hazard ratio (HR) of new-onset psoriasis. We also calculated HRs for psoriasis according to treatment, genetic, and lifestyle factors in a regional cohort of 8987 patients.RESULTS: In the nationwide cohort, 599 patients with breast cancer were diagnosed with psoriasis during a median follow-up of 5.1 years compared to 2795 cases in the matched reference individuals. This corresponded to an incidence rate of 1.9/1000 person-years in breast cancer patients vs. 1.7/1000 person-years in matched reference individuals. Breast cancer patients were at an increased risk of psoriasis (HR = 1.17; 95% confidence interval (CI) = 1.07-1.28), especially its most common subtype (psoriasis vulgaris; HR = 1.33; 95% CI = 1.17-1.52). The risk of psoriasis vulgaris was highest shortly after diagnosis but remained increased up to 12 years. Treatment-specific analyses indicated a higher risk of psoriasis in patients treated with radiotherapy (HR = 2.44; 95% CI = 1.44-4.12) and mastectomy (HR = 1.54, 95% CI = 1.03-2.31). Apart from treatment-specific effects, we identified genetic predisposition, obesity, and smoking as independent risk factors for psoriasis in breast cancer patients.CONCLUSIONS: The incidence of psoriasis is slightly elevated among patients with breast cancer, with treatment, lifestyle, and genetic factors defining the individual risk profile.
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