| 1. |
- Cheng, THT, et al.
(author)
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Meta-analysis of genome-wide association studies identifies common susceptibility polymorphisms for colorectal and endometrial cancer near SH2B3 and TSHZ1
- 2015
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In: Scientific reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 5, s. 17369-
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Journal article (peer-reviewed)abstract
- High-risk mutations in several genes predispose to both colorectal cancer (CRC) and endometrial cancer (EC). We therefore hypothesised that some lower-risk genetic variants might also predispose to both CRC and EC. Using CRC and EC genome-wide association series, totalling 13,265 cancer cases and 40,245 controls, we found that the protective allele [G] at one previously-identified CRC polymorphism, rs2736100 near TERT, was associated with EC risk (odds ratio (OR) = 1.08, P = 0.000167); this polymorphism influences the risk of several other cancers. A further CRC polymorphism near TERC also showed evidence of association with EC (OR = 0.92; P = 0.03). Overall, however, there was no good evidence that the set of CRC polymorphisms was associated with EC risk and neither of two previously-reported EC polymorphisms was associated with CRC risk. A combined analysis revealed one genome-wide significant polymorphism, rs3184504, on chromosome 12q24 (OR = 1.10, P = 7.23 × 10−9) with shared effects on CRC and EC risk. This polymorphism, a missense variant in the gene SH2B3, is also associated with haematological and autoimmune disorders, suggesting that it influences cancer risk through the immune response. Another polymorphism, rs12970291 near gene TSHZ1, was associated with both CRC and EC (OR = 1.26, P = 4.82 × 10−8), with the alleles showing opposite effects on the risks of the two cancers.
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| 3. |
- Kuhle, J., et al.
(author)
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Conversion from clinically isolated syndrome to multiple sclerosis: A large multicentre study
- 2015
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In: Multiple Sclerosis Journal. - : SAGE Publications. - 1352-4585 .- 1477-0970. ; 21:8, s. 1013-1024
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Journal article (peer-reviewed)abstract
- Background and objective: We explored which clinical and biochemical variables predict conversion from clinically isolated syndrome (CIS) to clinically definite multiple sclerosis (CDMS) in a large international cohort. Methods: Thirty-three centres provided serum samples from 1047 CIS cases with at least two years' follow-up. Age, sex, clinical presentation, T2-hyperintense lesions, cerebrospinal fluid (CSF) oligoclonal bands (OCBs), CSF IgG index, CSF cell count, serum 25-hydroxyvitamin D3 (25-OH-D), cotinine and IgG titres against Epstein-Barr nuclear antigen 1 (EBNA-1) and cytomegalovirus were tested for association with risk of CDMS. Results: At median follow-up of 4.31 years, 623 CIS cases converted to CDMS. Predictors of conversion in multivariable analyses were OCB (HR = 2.18, 95% CI = 1.71-2.77, p < 0.001), number of T2 lesions (two to nine lesions vs 0/1 lesions: HR = 1.97, 95% CI = 1.52-2.55, p < 0.001; >9 lesions vs 0/1 lesions: HR = 2.74, 95% CI = 2.04-3.68, p < 0.001) and age at CIS (HR per year inversely increase = 0.98, 95% CI = 0.98-0.99, p < 0.001). Lower 25-OH-D levels were associated with CDMS in univariable analysis, but this was attenuated in the multivariable model. OCB positivity was associated with higher EBNA-1 IgG titres. Conclusions: We validated MRI lesion load, OCB and age at CIS as the strongest independent predictors of conversion to CDMS in this multicentre setting. A role for vitamin D is suggested but requires further investigation.
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| 5. |
- O'Mara, TA, et al.
(author)
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Identification of nine new susceptibility loci for endometrial cancer
- 2018
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In: Nature communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 9:1, s. 3166-
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Journal article (peer-reviewed)abstract
- Endometrial cancer is the most commonly diagnosed cancer of the female reproductive tract in developed countries. Through genome-wide association studies (GWAS), we have previously identified eight risk loci for endometrial cancer. Here, we present an expanded meta-analysis of 12,906 endometrial cancer cases and 108,979 controls (including new genotype data for 5624 cases) and identify nine novel genome-wide significant loci, including a locus on 12q24.12 previously identified by meta-GWAS of endometrial and colorectal cancer. At five loci, expression quantitative trait locus (eQTL) analyses identify candidate causal genes; risk alleles at two of these loci associate with decreased expression of genes, which encode negative regulators of oncogenic signal transduction proteins (SH2B3 (12q24.12) and NF1 (17q11.2)). In summary, this study has doubled the number of known endometrial cancer risk loci and revealed candidate causal genes for future study.
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| 6. |
- Vanzella, E., et al.
(author)
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An extremely metal-poor star complex in the reionization era : Approaching Population III stars with JWST
- 2023
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In: Astronomy and Astrophysics. - 0004-6361 .- 1432-0746. ; 678
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Journal article (peer-reviewed)abstract
- We present JWST/Near Infrared Spectrograph (NIRSpec) integral field spectroscopy (IFS) of a lensed Population III candidate stellar complex (dubbed Lensed And Pristine 1, LAP1), with a lensing-corrected stellar mass of ≲104 M⊙ and an absolute luminosity of MUV > −11.2 (mUV > 35.6), confirmed at redshift 6.639 ± 0.004. The system is strongly amplified (μ ≳ 100) by straddling a critical line of the Hubble Frontier Field galaxy cluster MACS J0416. Although the stellar continuum is currently not detected in the Hubble and JWST/Near Infrared Camera (NIRCam) and Near Infrared Imager and Slitless Spectrograph (NIRISS) imaging, arclet-like shapes of Lyman and Balmer lines, Lyα, Hγ, Hβ and Hα are detected with NIRSpec IFS with signal-to-noise ratios (S/N) of approximately 5 − 13 and large equivalent widths (> 300 − 2000 Å), along with a remarkably weak [O III]λλ4959, 5007 at S/N ≃ 4. LAP1 shows a large ionizing photon production efficiency, log(ξion[erg Hz−1]) > 26. From the metallicity indexes R23 = ([O III] + [O II])/Hβ ≲ 0.74 and R3 = ([O III]/Hβ) = 0.55 ± 0.14, we derive an oxygen abundance of 12 + log(O/H)≲6.3. Intriguingly, the Hα emission is also measured in mirrored subcomponents where no [O III] is detected, providing even more stringent upper limits on the metallicity if in situ star formation is ongoing in this region (12 + log(O/H) < 6). The formal stellar mass limit of the subcomponents would correspond to ∼103 M⊙ or MUV fainter than −10. Alternatively, this metal-free, pure line-emitting region could be the first case of a fluorescing H I gas region induced by transverse escaping ionizing radiation from a nearby star complex. The presence of large equivalent-width hydrogen lines and the deficiency of metal lines in such a small region make LAP1 the most metal-poor star-forming region currently known in the reionization era and a promising site that may host isolated, pristine stars.
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- Bortolini, Giacomo, 1996-, et al.
(author)
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The spatially resolved star formation history of the dwarf spiral galaxy NGC 5474
- 2024
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In: Monthly notices of the Royal Astronomical Society. - 0035-8711 .- 1365-2966. ; 527:3, s. 5339-5355
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Journal article (peer-reviewed)abstract
- We study the resolved stellar populations and derive the star formation history of NGC 5474, a peculiar star-forming dwarf galaxy at a distance of ∼7 Mpc, using Hubble Space Telescope Advanced Camera for Surveys data from the Legacy Extragalactic UV Survey (LEGUS) programme. We apply an improved colour–magnitude diagram fitting technique based on the code SFERA and use the latest PARSEC–COLIBRI stellar models. Our results are the following. The off-centre bulge-like structure, suggested to constitute the bulge of the galaxy, is dominated by star formation (SF) activity initiated 14 Gyr ago and lasted at least up to 1 Gyr ago. Nevertheless, this component shows clear evidence of prolonged SF activity (lasting until ∼10 Myr ago). We estimate the total stellar mass of the bulge-like structure to be (5.0 ± 0.3) × 108 M⊙. Such a mass is consistent with published suggestions that this structure is in fact an independent system orbiting around and not within NGC 5474’s disc. The stellar overdensity located to the South–West of the bulge-like structure shows a significant SF event older than 1 Gyr, while it is characterized by two recent peaks of SF, around ∼10 and ∼100 Myr ago. In the last Gyr, the behaviour of the stellar disc is consistent with what is known in the literature as ‘gasping’. The synchronized burst at 10–35 Myr in all components might hint to the recent gravitational interaction between the stellar bulge-like structure and the disc of NGC 5474.
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| 15. |
- Sacchi, E., et al.
(author)
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Star Formation Histories of the LEGUS Dwarf Galaxies. II. Spatially Resolved Star Formation History of the Magellanic Irregular NGC 4449
- 2018
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In: Astrophysical Journal. - : American Astronomical Society. - 0004-637X .- 1538-4357. ; 857:1
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Journal article (peer-reviewed)abstract
- We present a detailed study of the Magellanic irregular galaxy NGC 4449 based on both archival and new photometric data from the Legacy Extragalactic UV Survey, obtained with the Hubble Space Telescope Advanced Camera for Surveys and Wide Field Camera 3. Thanks to its proximity ( D = 3.82 +/- 0.27 Mpc), we reach stars 3 mag fainter than the tip of the red giant branch in the F814W filter. The recovered star formation history (SFH) spans the whole Hubble time, but due to the age-metallicity degeneracy of the red giant branch stars, it is robust only over the lookback time reached by our photometry, i.e., similar to 3 Gyr. The most recent peak of star formation (SF) is around 10 Myr ago. The average surface density SF rate over the whole galaxy lifetime is 0.01 M-circle dot yr(-1) kpc(-2). From our study, it emerges that NGC. 4449 has experienced a fairly continuous SF regime in the last 1 Gyr, with peaks and dips whose SF rates differ only by a factor of a few. The very complex and disturbed morphology of NGC. 4449 makes it an interesting galaxy for studies of the relationship between interactions and starbursts, and our detailed and spatially resolved analysis of its SFH does indeed provide some hints on the connection between these two phenomena in this peculiar dwarf galaxy.
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