| 1. |
- Al-Jebari, Yahia, et al.
(författare)
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Cancer therapy and risk of congenital malformations in children fathered by men treated for testicular germ-cell cancer : A nationwide register study
- 2019
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Ingår i: PLoS Medicine. - : PUBLIC LIBRARY SCIENCE. - 1549-1277 .- 1549-1676. ; 16:6
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Tidskriftsartikel (refereegranskat)abstract
- Background Because of the potential mutagenic effects of chemo- and radiotherapy, there is concern regarding increased risk of congenital malformations (CMs) among children of fathers with cancer. Previous register studies indicate increased CM risk among children conceived after paternal cancer but lack data on oncological treatment. Increased CM risk was recently reported in children born before paternal cancer. This study aims to investigate whether anti-neoplastic treatment for testicular germ-cell cancer (TGCC) implies additional CM risk. Methods and findings In this nationwide register study, all singletons born in Sweden 1994-2014 (n = 2,027,997) were included. Paternal TGCC diagnoses (n = 2,380), anti-neoplastic treatment, and offspring CMs were gathered from the Swedish Norwegian Testicular Cancer Group (SWENOTECA) and the Swedish Medical Birth Register. Children were grouped based on +/- paternal TGCC; treatment regimen: surveillance (n = 1,340), chemotherapy (n = 2,533), or radiotherapy (n = 360); and according to time of conception: pre- (n = 2,770) or post-treatment (n = 1,437). Odds ratios (ORs) for CMs were calculated using logistic regression with adjustment for parental ages, maternal body mass index (BMI), and maternal smoking. Children conceived before a specific treatment acted as reference for children conceived after the same treatment. Among children fathered by men with TGCC (n = 4,207), 184 had a CM. The risk of malformations was higher among children of fathers with TGCC compared with children fathered by men without TGCC (OR 1.28, 95% confidence interval [CI] 1.19-1.38, p = 0.001, 4.4% versus 3.5%). However, no additional risk increase was associated with oncological treatment when comparing post-treatment-to pretreatment-conceived children (chemotherapy, OR = 0.82, 95% CI 0.54-1.25, p = 0.37, 4.1% versus 4.6%; radiotherapy, OR = 1.01, 95% CI 0.25-4.12, p = 0.98, 3.2% versus 3.0%). Study limitations include lack of data on use of cryopreserved or donor sperm and on seminoma patients for the period 1995-2000-both tending to decrease the difference between the groups with TGCC and without TGCC. Furthermore, the power of analyses on chemotherapy intensity and radiotherapy was limited. Conclusions No additional increased risk of CMs was observed in children of men with TGCC treated with radio- or chemotherapy. However, paternal TGCC per se was associated with modestly increased risk for offspring malformations. Clinically, this information can reassure concerned patients.
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| 2. |
- Buckland, Genevieve, et al.
(författare)
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Adherence to a Mediterranean diet and risk of gastric adenocarcinoma within the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort study
- 2010
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Ingår i: American Journal of Clinical Nutrition. - : Elsevier BV. - 0002-9165 .- 1938-3207. ; 91:2, s. 381-390
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: The Mediterranean dietary pattern is believed to protect against cancer, although evidence from cohort studies that have examined particular cancer sites is limited. OBJECTIVE: We aimed to explore the association between adherence to a relative Mediterranean diet (rMED) and incident gastric adenocarcinoma (GC) within the European Prospective Investigation into Cancer and Nutrition study. DESIGN: The study included 485,044 subjects (144,577 men) aged 35-70 y from 10 European countries. At recruitment, dietary and lifestyle information was collected. An 18-unit rMED score, incorporating 9 key components of the Mediterranean diet, was used to estimate rMED adherence. The association between rMED and GC with respect to anatomic location (cardia and noncardia) and histologic types (diffuse and intestinal) was investigated. A calibration study in a subsample was used to control for dietary measurement error. RESULTS: After a mean follow-up of 8.9 y, 449 validated incident GC cases were identified and used in the analysis. After stratification by center and age and adjustment for recognized cancer risk factors, high compared with low rMED adherence was associated with a significant reduction in GC risk (hazard ratio: 0.67; 95% CI: 0.47, 0.94). A 1-unit increase in the rMED score was associated with a decreased risk of GC of 5% (95% CI: 0.91, 0.99). There was no evidence of heterogeneity between different anatomic locations or histologic types. The calibrated results showed similar trends (overall hazard ratio for GC: 0.93; 95% CI: 0.89, 0.99). CONCLUSION: Greater adherence to an rMED is associated with a significant reduction in the risk of incident GC.
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| 3. |
- Dalgaard, Marlene D., et al.
(författare)
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A genome-wide association study of men with symptoms of testicular dysgenesis syndrome and its network biology interpretation
- 2012
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Ingår i: Journal of Medical Genetics. - : BMJ. - 0022-2593 .- 1468-6244. ; 49:1, s. 58-65
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Tidskriftsartikel (refereegranskat)abstract
- Background Testicular dysgenesis syndrome (TDS) is a common disease that links testicular germ cell cancer, cryptorchidism and some cases of hypospadias and male infertility with impaired development of the testis. The incidence of these disorders has increased over the last few decades, and testicular cancer now affects 1% of the Danish and Norwegian male population. Methods To identify genetic variants that span the four TDS phenotypes, the authors performed a genome-wide association study (GWAS) using Affymetrix Human SNP Array 6.0 to screen 488 patients with symptoms of TDS and 439 selected controls with excellent reproductive health. Furthermore, they developed a novel integrative method that combines GWAS data with other TDS-relevant data types and identified additional TDS markers. The most significant findings were replicated in an independent cohort of 671 Nordic men. Results Markers located in the region of TGFBR3 and BMP7 showed association with all TDS phenotypes in both the discovery and replication cohorts. An immunohistochemistry investigation confirmed the presence of transforming growth factor beta receptor type III (TGFBR3) in peritubular and Leydig cells, in both fetal and adult testis. Single-nucleotide polymorphisms in the KITLG gene showed significant associations, but only with testicular cancer. Conclusions The association of single-nucleotide polymorphisms in the TGFBR3 and BMP7 genes, which belong to the transforming growth factor b signalling pathway, suggests a role for this pathway in the pathogenesis of TDS. Integrating data from multiple layers can highlight findings in GWAS that are biologically relevant despite having border significance at currently accepted statistical levels.
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| 4. |
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| 5. |
- Hober, Sophia, Professor, 1965-, et al.
(författare)
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Systematic evaluation of SARS-CoV-2 antigens enables a highly specific and sensitive multiplex serological COVID-19 assay
- 2021
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Ingår i: Clinical & Translational Immunology. - : Wiley. - 2050-0068. ; 10:7
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Tidskriftsartikel (refereegranskat)abstract
- Objective. The COVID-19 pandemic poses an immense need for accurate, sensitive and high-throughput clinical tests, and serological assays are needed for both overarching epidemiological studies and evaluating vaccines. Here, we present the development and validation of a high-throughput multiplex bead-based serological assay. Methods. More than 100 representations of SARS-CoV-2 proteins were included for initial evaluation, including antigens produced in bacterial and mammalian hosts as well as synthetic peptides. The five best-performing antigens, three representing the spike glycoprotein and two representing the nucleocapsid protein, were further evaluated for detection of IgG antibodies in samples from 331 COVID-19 patients and convalescents, and in 2090 negative controls sampled before 2020. Results. Three antigens were finally selected, represented by a soluble trimeric form and the S1-domain of the spike glycoprotein as well as by the C-terminal domain of the nucleocapsid. The sensitivity for these three antigens individually was found to be 99.7%, 99.1% and 99.7%, and the specificity was found to be 98.1%, 98.7% and 95.7%. The best assay performance was although achieved when utilising two antigens in combination, enabling a sensitivity of up to 99.7% combined with a specificity of 100%. Requiring any two of the three antigens resulted in a sensitivity of 99.7% and a specificity of 99.4%. Conclusion. These observations demonstrate that a serological test based on a combination of several SARS-CoV-2 antigens enables a highly specific and sensitive multiplex serological COVID-19 assay.
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| 6. |
- Lécuyer, Lucie, et al.
(författare)
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Inflammatory potential of the diet and association with risk of differentiated thyroid cancer in the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort
- 2022
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Ingår i: European Journal of Nutrition. - : Springer. - 1436-6207 .- 1436-6215. ; 61, s. 3625-3635
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Tidskriftsartikel (refereegranskat)abstract
- Purpose: Chronic inflammation is thought to initiate or promote differentiated thyroid cancer (DTC) and previous studies have shown that diet can modulate this inflammatory process. We aimed to evaluate the association of several dietary scores reflecting the inflammatory potential of the diet with DTC risk.Methods: Within the EPIC cohort, 450,063 participants were followed during a mean period of 14 years, and 712 newly incident DTC cases were identified. Associations between four dietary inflammatory scores [the dietary inflammatory index (DII®) and two energy-adjusted derivatives (the E-DIIr and the E-DIId), and the Inflammatory Score of the Diet (ISD)] and DTC risk were evaluated in the EPIC cohort using multivariable Cox regression models.Results: Positive associations were observed between DTC risk and the DIIs (HR for 1 SD increase in DII: 1.11, 95%CI: 1.01, 1.23, similar results for its derivatives), but not with the ISD (HR for 1 SD increase: 1.04, 95% CI 0.93, 1.16).Conclusion: Diet-associated inflammation, as estimated by the DII and its derivatives, was weakly positively associated with DTC risk in a European adult population. These results suggesting that diet-associated inflammation acts in the etiology of DTC need to be validated in independent studies.
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| 7. |
- Persdotter Hedlund, Gabriella, et al.
(författare)
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Fetal antigen 1 (FA1) in the adult rat adrenal gland, ovary and pituitary gland
- 2003
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Ingår i: In Vivo. - 0258-851X .- 1791-7549. ; 17:1, s. 1-4
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Tidskriftsartikel (refereegranskat)abstract
- Fetal antigen 1 (FA1) is a circulating glycoprotein containing six epidermal growth factor (EGF)-like repeats. FA1's larger membrane-bound precursor is defined by the cDNAs referred to as either human delta-like (dlk) or human adrenal specific cDNA, pG2. In rodents FA1 has also been studied under the names of preadipocyte factor 1 (Pref-1), and zona glomerulosa-specific factor (ZOG). FA1 is abundantly expressed in fetal tissues, but in the mature cells of the adult organism the tissue presence of the protein seems to be restricted to neuroendocrine tissues. The present study demonstrates FA1 localisation in endocrine tissues of the adult female rat in which the protein was found present in the medulla and the zona glomerulosa of the cortex of the adrenal glands, in the pars distalis of the adenohypophysis, and in the ovarian granulosa lutein cells. No staining was found in the pancreas, which is in contrast to what has been described in the human.
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| 8. |
- Rossi, Rachele, et al.
(författare)
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A Proof of Principle Proteomic Study Detects Dystrophin in Human Plasma : Implications in DMD Diagnosis and Clinical Monitoring
- 2023
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Ingår i: International Journal of Molecular Sciences. - : MDPI AG. - 1661-6596 .- 1422-0067. ; 24:6
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Tidskriftsartikel (refereegranskat)abstract
- Duchenne muscular dystrophy (DMD) is a rare neuromuscular disease caused by pathogenic variations in the DMD gene. There is a need for robust DMD biomarkers for diagnostic screening and to aid therapy monitoring. Creatine kinase, to date, is the only routinely used blood biomarker for DMD, although it lacks specificity and does not correlate with disease severity. To fill this critical gap, we present here novel data about dystrophin protein fragments detected in human plasma by a suspension bead immunoassay using two validated anti-dystrophin-specific antibodies. Using both antibodies, a reduction of the dystrophin signal is detected in a small cohort of plasma samples from DMD patients when compared to healthy controls, female carriers, and other neuromuscular diseases. We also demonstrate the detection of dystrophin protein by an antibody-independent method using targeted liquid chromatography mass spectrometry. This last assay detects three different dystrophin peptides in all healthy individuals analysed and supports our finding that dystrophin protein is detectable in plasma. The results of our proof-of-concept study encourage further studies in larger sample cohorts to investigate the value of dystrophin protein as a low invasive blood biomarker for diagnostic screening and clinical monitoring of DMD.
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