Background
A recent association study identified a common variant (rs9790517) at 4q24 to be associated with breast cancer risk. Independent association signals and potential functional variants in this locus have not been explored.
Methods
We conducted a fine-mapping analysis in 55,540 breast cancer cases and 51,168 controls from the Breast Cancer Association Consortium.
Results
Conditional analyses identified two independent association signals among women of European ancestry, represented by rs9790517 (conditional p = 2.51 × 10−4; OR = 1.04; 95% CI 1.02–1.07) and rs77928427 (p = 1.86 × 10−4; OR = 1.04; 95% CI 1.02–1.07). Functional annotation using data from the Encyclopedia of DNA Elements (ENCODE) project revealed two putative functional variants, rs62331150 and rs73838678 in linkage disequilibrium (LD) with rs9790517 (r2 ≥ 0.90) residing in the active promoter or enhancer, respectively, of the nearest gene, TET2. Both variants are located in DNase I hypersensitivity and transcription factor binding sites. Using data from both The Cancer Genome Atlas (TCGA) and Molecular Taxonomy of Breast Cancer International Consortium (METABRIC), we showed that rs62331150 was associated with level of expression of TET2 in breast normal and tumor tissue.
Conclusion
Our study identified two independent association signals at 4q24 in relation to breast cancer risk and suggested that observed association in this locus may be mediated through the regulation of TET2.
Impact
Fine-mapping study with large sample size warranted for identification of independent loci for breast cancer risk.
Background
Covid-19 has placed unprecedented demand on healthcare systems and on healthcare professionals. There have been concerns about the risk of distress, moral injury and burnout among healthcare professionals, especially doctors.
Aim
To assess the effect of the ongoing Covid-19 pandemic on Irish doctors by investigating the incidence of burnout and long covid among senior medical staff in Ireland.
Methods
This is a cross-sectional pilot study of the prevalence of burnout and long covid among senior physicians. A survey was sent by email to members of the Irish Hospital Consultant’s Association. The survey included measures of mental and physical health and the 2-item Maslach Burnout Scale (MBS-2). The study explored the experience of delivering health care in the context of a pandemic and experience of the long covid syndrome.
Results
A total of 114 responses were received. Three-quarters 77% (
N
= 88) screened positive for burnout on the MBS, with mean score of 5.6 (SD3.3), nearly double the cut-off for burnout. Nearly two-thirds (64%,
n
= 72) reported that Covid-19 has had an adverse effect on their mental health. One-quarter reported that they or colleagues had experience of ‘long-covid’ secondary to the virus.
Conclusion
More comprehensive evaluation of the effect of the pandemic on front-line staff is needed to identify the extent of the problem and the factors which contribute to it. This will inform measures to mitigate these effects.
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