| 1. |
- Lawrenson, Kate, et al.
(författare)
-
Functional mechanisms underlying pleiotropic risk alleles at the 19p13.1 breast-ovarian cancer susceptibility locus
- 2016
-
Ingår i: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 7
-
Tidskriftsartikel (refereegranskat)abstract
- A locus at 19p13 is associated with breast cancer (BC) and ovarian cancer (OC) risk. Here we analyse 438 SNPs in this region in 46,451 BC and 15,438 OC cases, 15,252 BRCA1 mutation carriers and 73,444 controls and identify 13 candidate causal SNPs associated with serous OC (P=9.2 × 10-20), ER-negative BC (P=1.1 × 10-13), BRCA1-associated BC (P=7.7 × 10-16) and triple negative BC (P-diff=2 × 10-5). Genotype-gene expression associations are identified for candidate target genes ANKLE1 (P=2 × 10-3) and ABHD8 (P<2 × 10-3). Chromosome conformation capture identifies interactions between four candidate SNPs and ABHD8, and luciferase assays indicate six risk alleles increased transactivation of the ADHD8 promoter. Targeted deletion of a region containing risk SNP rs56069439 in a putative enhancer induces ANKLE1 downregulation; and mRNA stability assays indicate functional effects for an ANKLE1 3′-UTR SNP. Altogether, these data suggest that multiple SNPs at 19p13 regulate ABHD8 and perhaps ANKLE1 expression, and indicate common mechanisms underlying breast and ovarian cancer risk.
|
|
| 2. |
- Ding, Yuan C, et al.
(författare)
-
A nonsynonymous polymorphism in IRS1 modifies risk of developing breast and ovarian cancers in BRCA1 and ovarian cancer in BRCA2 mutation carriers
- 2012
-
Ingår i: Cancer Epidemiology, Biomarkers and Prevention. - : American Association for Cancer Research. - 1055-9965 .- 1538-7755. ; 21:8, s. 1362-1370
-
Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: We previously reported significant associations between genetic variants in insulin receptor substrate 1 (IRS1) and breast cancer risk in women carrying BRCA1 mutations. The objectives of this study were to investigate whether the IRS1 variants modified ovarian cancer risk and were associated with breast cancer risk in a larger cohort of BRCA1 and BRCA2 mutation carriers.METHODS: IRS1 rs1801123, rs1330645, and rs1801278 were genotyped in samples from 36 centers in the Consortium of Investigators of Modifiers of BRCA1/2 (CIMBA). Data were analyzed by a retrospective cohort approach modeling the associations with breast and ovarian cancer risks simultaneously. Analyses were stratified by BRCA1 and BRCA2 status and mutation class in BRCA1 carriers.RESULTS: Rs1801278 (Gly972Arg) was associated with ovarian cancer risk for both BRCA1 (HR, 1.43; 95% confidence interval (CI), 1.06-1.92; P = 0.019) and BRCA2 mutation carriers (HR, 2.21; 95% CI, 1.39-3.52, P = 0.0008). For BRCA1 mutation carriers, the breast cancer risk was higher in carriers with class II mutations than class I mutations (class II HR, 1.86; 95% CI, 1.28-2.70; class I HR, 0.86; 95%CI, 0.69-1.09; P(difference), 0.0006). Rs13306465 was associated with ovarian cancer risk in BRCA1 class II mutation carriers (HR, 2.42; P = 0.03).CONCLUSION: The IRS1 Gly972Arg single-nucleotide polymorphism, which affects insulin-like growth factor and insulin signaling, modifies ovarian cancer risk in BRCA1 and BRCA2 mutation carriers and breast cancer risk in BRCA1 class II mutation carriers.Impact: These findings may prove useful for risk prediction for breast and ovarian cancers in BRCA1 and BRCA2 mutation carriers.
|
|
| 3. |
- Costa, Lorenzo, et al.
(författare)
-
Maturation of the vertebral ring apophysis is delayed in girls with adolescent idiopathic scoliosis compared to the normal population
- 2024
-
Ingår i: SPINE DEFORMITY. - : SPRINGER. - 2212-134X.
-
Tidskriftsartikel (refereegranskat)abstract
- Purpose The ring apophysis is a secondary ossification center on both sides of each vertebral body, to which the annulus of the intervertebral disc inserts. Recently, its pattern of ossification and fusion to the vertebral body was described for the normal growing spine. The aim of the present study was to investigate the ossification and fusion of the ring apophysis in patients with adolescent idiopathic scoliosis (AIS) and compare it to the normal growing population.Methods Ring apophysis maturation along the entire thoracic and lumbar spine was analyzed on CT scans of 99 female, pre-operative AIS patients and compared to 134 CT scans of non-scoliotic girls, aged 12 to 20.Results The ring apophysis maturation in AIS patients was delayed at all spinal levels in AIS patients compared to non-scoliotic controls. Ossification starts at T4-T11 at age 12, followed by T1-T5 and L3-S1 at age 15. The fusion process in AIS patients continues longer in the midthoracic region as compared to the other regions and as compared to non-scoliotic controls, with many incomplete fusions still at age 20.Conclusion The ring apophysis maturation in AIS is delayed compared to that in the normal population and lasts longer in the mid/low thoracic spine. Delayed maturation of the spine's most important stabilizer, while the body's dimensions continue to increase, could be part of the patho-mechanism of AIS.
|
|
| 4. |
- Trizuljak, Jakub, et al.
(författare)
-
Clinical features and survival of patients with indolent systemic mastocytosis defined by the updated WHO classification
- 2020
-
Ingår i: Allergy. European Journal of Allergy and Clinical Immunology. - : Wiley. - 0105-4538 .- 1398-9995. ; 75:8, s. 1927-1938
-
Tidskriftsartikel (refereegranskat)abstract
- Background: In indolent systemic mastocytosis (ISM), several risk factors of disease progression have been identified. Previous studies, performed with limited patient numbers, have also shown that the clinical course in ISM is stable and comparable to that of cutaneous mastocytosis (CM). The aim of this project was to compare the prognosis of patients with ISM with that of patients with CM.Methods: We employed a dataset of 1993 patients from the registry of the European Competence Network on Mastocytosis (ECNM) to compare outcomes of ISM and CM.Results: We found that overall survival (OS) is worse in ISM compared to CM. Moreover, in patients with typical ISM, bone marrow mastocytosis (BMM), and smoldering SM (SSM), 4.1% of disease progressions have been observed (4.9% of progressions in typical ISM group, 1.7% in BMM, and 9.4% in SSM). Progressions to advanced SM were observed in 2.9% of these patients. In contrast, six patients with CM (1.7%) converted to ISM and no definitive progression to advanced SM was found. No significant differences in OS and event-free survival (EFS) were found when comparing ISM, BMM, and SSM. Higher risk of both progression and death was significantly associated with male gender, worse performance status, and organomegaly.Conclusion: Our data confirm the clinical impact of the WHO classification that separates ISM from CM and from other SM variants.
|
|
| 5. |
- Vasiliu, Anca, et al.
(författare)
-
Tuberculosis incidence in foreign-born people residing in European countries in 2020
- 2023
-
Ingår i: Eurosurveillance. - : European Centre for Disease Prevention and Control (ECDC). - 1025-496X .- 1560-7917. ; 28:42
-
Tidskriftsartikel (refereegranskat)abstract
- Background: European-specific policies for tuberculosis (TB) elimination require identification of key populations that benefit from TB screening.Aim: We aimed to identify groups of foreign-born individuals residing in European countries that benefit most from targeted TB prevention screening.Methods: The Tuberculosis Network European Trials group collected, by cross-sectional survey, numbers of foreign-born TB patients residing in European Union (EU) countries, Iceland, Norway, Switzerland and the United Kingdom (UK) in 2020 from the 10 highest ranked countries of origin in terms of TB cases in each country of residence. Tuberculosis incidence rates (IRs) in countries of residence were compared with countries of origin.Results: Data on 9,116 foreign-born TB patients in 30 countries of residence were collected. Main countries of origin were Eritrea, India, Pakistan, Morocco, Romania and Somalia. Tuberculosis IRs were highest in patients of Eritrean and Somali origin in Greece and Malta (both > 1,000/100,000) and lowest among Ukrainian patients in Poland (3.6/100,000). They were mainly lower in countries of residence than countries of origin. However, IRs among Eritreans and Somalis in Greece and Malta were five times higher than in Eritrea and Somalia. Similarly, IRs among Eritreans in Germany, the Netherlands and the UK were four times higher than in Eritrea.Conclusions: Country of origin TB IR is an insufficient indicator when targeting foreign-born populations for active case finding or TB prevention policies in the countries covered here. Elimination strategies should be informed by regularly collected country-specific data to address rapidly changing epidemiology and associated risks.
|
|
