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| 5. |
- Gusev, A, et al.
(författare)
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Atlas of prostate cancer heritability in European and African-American men pinpoints tissue-specific regulation
- 2016
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Ingår i: Nature communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 7, s. 10979-
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Tidskriftsartikel (refereegranskat)abstract
- Although genome-wide association studies have identified over 100 risk loci that explain ∼33% of familial risk for prostate cancer (PrCa), their functional effects on risk remain largely unknown. Here we use genotype data from 59,089 men of European and African American ancestries combined with cell-type-specific epigenetic data to build a genomic atlas of single-nucleotide polymorphism (SNP) heritability in PrCa. We find significant differences in heritability between variants in prostate-relevant epigenetic marks defined in normal versus tumour tissue as well as between tissue and cell lines. The majority of SNP heritability lies in regions marked by H3k27 acetylation in prostate adenoc7arcinoma cell line (LNCaP) or by DNaseI hypersensitive sites in cancer cell lines. We find a high degree of similarity between European and African American ancestries suggesting a similar genetic architecture from common variation underlying PrCa risk. Our findings showcase the power of integrating functional annotation with genetic data to understand the genetic basis of PrCa.
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| 6. |
- Wang, Zhaoming, et al.
(författare)
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Imputation and subset-based association analysis across different cancer types identifies multiple independent risk loci in the TERT-CLPTM1L region on chromosome 5p15.33
- 2014
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Ingår i: Human Molecular Genetics. - : Oxford University Press (OUP). - 0964-6906 .- 1460-2083. ; 23:24, s. 6616-6633
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Tidskriftsartikel (refereegranskat)abstract
- Genome-wide association studies (GWAS) have mapped risk alleles for at least 10 distinct cancers to a small region of 63 000 bp on chromosome 5p15.33. This region harbors the TERT and CLPTM1L genes; the former encodes the catalytic subunit of telomerase reverse transcriptase and the latter may play a role in apoptosis. To investigate further the genetic architecture of common susceptibility alleles in this region, we conducted an agnostic subset-based meta-analysis (association analysis based on subsets) across six distinct cancers in 34 248 cases and 45 036 controls. Based on sequential conditional analysis, we identified as many as six independent risk loci marked by common single-nucleotide polymorphisms: five in the TERT gene (Region 1: rs7726159, P = 2.10 × 10(-39); Region 3: rs2853677, P = 3.30 × 10(-36) and PConditional = 2.36 × 10(-8); Region 4: rs2736098, P = 3.87 × 10(-12) and PConditional = 5.19 × 10(-6), Region 5: rs13172201, P = 0.041 and PConditional = 2.04 × 10(-6); and Region 6: rs10069690, P = 7.49 × 10(-15) and PConditional = 5.35 × 10(-7)) and one in the neighboring CLPTM1L gene (Region 2: rs451360; P = 1.90 × 10(-18) and PConditional = 7.06 × 10(-16)). Between three and five cancers mapped to each independent locus with both risk-enhancing and protective effects. Allele-specific effects on DNA methylation were seen for a subset of risk loci, indicating that methylation and subsequent effects on gene expression may contribute to the biology of risk variants on 5p15.33. Our results provide strong support for extensive pleiotropy across this region of 5p15.33, to an extent not previously observed in other cancer susceptibility loci.
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| 7. |
- Allen, N. E., et al.
(författare)
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Animal foods, protein, calcium and prostate cancer risk: the European Prospective Investigation into Cancer and Nutrition
- 2008
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Ingår i: British Journal of Cancer. - : Springer Science and Business Media LLC. - 1532-1827 .- 0007-0920. ; 98:9, s. 1574-1581
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Tidskriftsartikel (refereegranskat)abstract
- We examined consumption of animal foods, protein and calcium in relation to risk of prostate cancer among 142 251 men in the European Prospective Investigation into Cancer and Nutrition. Associations were examined using Cox regression, stratified by recruitment centre and adjusted for height, weight, education, marital status and energy intake. After an average of 8.7 years of follow-up, there were 2727 incident cases of prostate cancer, of which 1131 were known to be localised and 541 advanced-stage disease. A high intake of dairy protein was associated with an increased risk, with a hazard ratio for the top versus the bottom fifth of intake of 1.22 (95% confidence interval (CI): 1.07-1.41, P-trend = 0.02). After calibration to allow for measurement error, we estimated that a 35-g day(-1) increase in consumption of dairy protein was associated with an increase in the risk of prostate cancer of 32% (95% CI: 1-72%, P-trend = 0.04). Calcium from dairy products was also positively associated with risk, but not calcium from other foods. The results support the hypothesis that a high intake of protein or calcium from dairy products may increase the risk for prostate cancer.
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| 8. |
- Hedlund, P. O., et al.
(författare)
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Parenteral estrogen versus combined androgen deprivation in the treatment of metastatic prostatic cancer : Part 2. Final evaluation of the Scandinavian Prostatic Cancer Group (SPCG) Study No. 5
- 2008
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Ingår i: Scandinavian Journal of Urology and Nephrology. - : Informa UK Limited. - 0036-5599 .- 1651-2065. ; 42:3, s. 220-229
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Tidskriftsartikel (refereegranskat)abstract
- Objective. To compare parenteral estrogen therapy in the form of high-dose polyestradiol phosphate (PEP, Estradurin®) with combined androgen deprivation (CAD) in the treatment of prostate cancer patients with skeletal metastases. The aim of the study was to compare anticancer efficacy and adverse events, especially cardiovascular events. Material and methods. In total, 910 eligible patients with T0-4, NX, M1, G1-3 prostate cancer with an Eastern Cooperative Oncology Group performance status of 0-2 were randomized to treatment with either PEP 240mg i.m. twice a month for 2months and thereafter monthly, or flutamide (Eulexin®) 250mg t.i.d. per os in combination with either triptorelin (Decapeptyl®) 3.75mg i.m. per month or on an optional basis bilateral orchidectomy. Results. At this final evaluation of the trial 855 of the 910 patients were dead. There was no difference between the treatment groups in terms of biochemical or clinical progression-free survival or in overall or disease-specific survival. There was no difference in cardiovascular mortality, but a significant increase in non-fatal cardiovascular events in the PEP arm (p<0.05) predominantly caused by an increase in ischemic heart and heart decompensation events. There were 18 grave skeletal events in the CAD group but none in the PEP group (p=0.001). Conclusions. PEP has an anticancer efficacy equal to CAD and does not increase cardiovascular mortality in metastasized patients, but carries a significant risk of non-fatal cardiovascular events, which should be balanced against the skeletal complications in the CAD group. It is feasible to use Estradurin in the primary or secondary endocrine treatment of metastasized patients without prominent cardiac risk factors and especially those with osteoporosis. © 2008 Taylor & Francis.
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- Hallmans, Göran, et al.
(författare)
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Rye, lignans and human health
- 2003
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Ingår i: Proceedings of the Nutrition Society. - 0029-6651 .- 1475-2719. ; 62:1, s. 193-9
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Tidskriftsartikel (refereegranskat)abstract
- Rye bran contains a high content not only of dietary fibre, but also of plant lignans and other bioactive compounds in the so-called dietary fibre complex. Blood concentrations of lignans such as enterolactone have been used as biomarkers of intake of lignan-rich plant food. At present,evidence from studies in human subjects does not warrant the conclusion that rye, whole grains orphyto-oestrogens protect against cancer. Some studies, however, have pointed in that direction,especially in relation to cancers of the upper digestive tract. A number of prospective epidemiological studies have clearly shown a protective effect of wholegrain cereals against myocardial infarctions. A corresponding protective effect against diabetes and ischaemic stroke(brain infarct) has also been demonstrated. It seems reasonable to assume that these protective effects are associated with one or more factors in the dietary fibre complex.
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| 12. |
- Scelo, G, et al.
(författare)
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International cancer seminars : a focus on kidney cancer.
- 2016
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Ingår i: Annals of Oncology. - : Elsevier BV. - 0923-7534 .- 1569-8041. ; 27:8, s. 1382-5
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Tidskriftsartikel (refereegranskat)abstract
- Recent years have seen important advances in our understanding of the etiology, biology and genetics of kidney cancer. To summarize important achievements and identify prominent research questions that remain, a workshop was organized by IARC and the US NCI. A series of 'difficult questions' were formulated, which should be given future priority in the areas of population, genomic and clinical research.
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| 14. |
- Andreasson, A., et al.
(författare)
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Fosfomycin versus Ciprofloxacin as transrectal prostatebiopsy antibiotic prophylaxis an open randomized controlled multicenter drug trial
- 2023
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Ingår i: European Urology. - : Elsevier. - 0302-2838 .- 1873-7560. ; 83:Suppl. 1, s. S180-S180
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- Introduction & Objectives: Antibiotic prophylaxis are administered as a routine to decrease the risk for septic complications following transrectal prostate biopsy. Fosfomycin administered 1 h or more prior to biopsy has equal or better infectious complication rates as compared to Ciprofloxacin in both prospective and retrospective studies from countries with high rates of antibiotic resistance. The aim of this study was to investigate if Fosfomycin administered immediately prior to prostate biopsy was as effective as Ciprofloxacin in Sweden, a country with low rates of antibiotic resistance.Materials & Methods: A randomized, controlled, open, multicenter, non-inferiority-study including men of all ages undergoing transrectal prostate biopsy was performed in the urology departments of three Swedish hospitals. The total number of patients were planned for 3448, divided into low and high infection risk groups. The low-risk group was randomized to either one dose of Fosfomycin 3g or Ciprofloxacin 750mg before biopsy. The high-risk group was randomized to either two doses of Fosfomycin 3g prior to biopsy and one more 24 h after biopsy or Ciprofloxacin 500mg once prior to biopsy and then twice daily for three days. The drugs were administered orally. All patients had a rectal swab for culture before and after biopsy. The endpoint was hospitalisation due to urinary tract infection within 14 days from biopsy, follow-up was performed with a phone interview.Results: The safety board prematurely interrupted the study after 42 included patients due to an unusual high number of hospitalisations. Four out of 20 patients (20%), three in the low-risk group and one in the high-risk group, had been hospitalised due to urosepsis in the Fosfomycin group. One further patient described fever symptoms but did not seek health care. No patient in the Ciprofloxacin group (n=21) described symptoms of infection from the urinary tract. One patient was lost to follow-up. A one-sided binomial test showed a p-value of <0.001. Two of the four hospitalised patients had a positive blood culture for Pseudomonas Aeruginosa and one had a positive rectal swab culture for Pseudomonas species both before and after biopsy.Conclusions: The study does not support the use of Fosfomycin administered immediately prior to prostate biopsy. The results may have been affected by the unexpected high number of Pseudomonas infections, a bacteria where Fosfomycin often lack effect. If Fosfomycin is to be used it should be with caution if Pseudomonas has been seen in earlier cultures
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| 15. |
- Beckmann, K., et al.
(författare)
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Radical radiotherapy for prostate cancer: patterns of care in Sweden 1998-2016
- 2020
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Ingår i: Acta Oncologica. - : Informa UK Limited. - 0284-186X .- 1651-226X. ; 59:5, s. 549-557
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Tidskriftsartikel (refereegranskat)abstract
- Introduction: Radiotherapy is an established treatment option for prostate cancer (PCa), both as primary treatment and secondary treatment after radical prostatectomy (RP). Since 1998, detailed data on radiotherapy delivered to Swedish men with PCa (e.g. treatment modalities, absorbed doses, fractionation) have been collated within PCa data Base Sweden (PCBaSe). This study reports patterns of radical radiotherapy for PCa in Sweden over the past two decades. Materials and methods: All men with non-metastatic PCa (1998-2016) who received external beam radiotherapy (EBRT) or high or low dose-rate brachytherapy (HDR-BT/LDR-BT) were identified in PCBaSe. Analyses included: trends in radiation techniques, fractionation patterns and total doses over time; PCa-specific survival comparing treatment in 2007-2017 with 1998-2006; and regional variation in type of primary radiotherapy. Results: About 20,876 men underwent primary radiotherapy. The main treatment modalities include conventionally fractionated (2.0 Gy/fraction) EBRT (51%), EBRT with HDR-BT boost (27%) and hypofractionated (>2.4 Gy/fraction) EBRT (11%). EBRT with photon or proton boost and HDR-BT and LDR-BT monotherapies were each used minimally. Use of dose-escalated EBRT (>74 Gy) and moderate hypofractionation increased over time, while use of HDR-BT declined. Considerable regional variation in treatment modalities was apparent. Risk of PCa death following primary radiotherapy had declined for intermediate-risk (HR: 0.60; 95%CI 0.47-0.87) and high-risk PCa (HR: 0.72; 95%CI 0.61-0.86). Discussion: Increased use of dose escalation and hypofractionated EBRT has occurred in Sweden over the past two decades, reflecting current evidence and practice guidelines. Disease-specific outcomes have also improved. Data collected in PCBaSe provide an excellent resource for further research into RT use in PCa management.
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- Häggström, S, et al.
(författare)
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Castration-induced reduction of vascular endothelial growth factor expression in benign human prostate tissue is lost in advanced prostate cancer.
- 2001
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Ingår i: BJU International. - 1464-4096 .- 1464-410X. ; 88:1, s. 110-6
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: To determine the role of vascular response in the castration-induced regression of benign and malignant human prostate tissue, as recent studies show that castration rapidly decreases blood flow and induces endothelial cell death, which may be important for subsequent epithelial cell death and involution of the glandular tissue of the prostate.MATERIALS AND METHODS: The expression of vascular endothelial growth factor (VEGF) and its receptors was analysed using the quantitative reverse transcriptase-polymerase chain reaction, in benign and tumour areas of core biopsies taken before, and approximately 1 week after castration therapy. The castration-induced VEGF response was related to therapy-induced changes in tumour cell apoptotic index and subsequent response in serum prostate-specific antigen (PSA). In another set of patients, serum VEGF was quantified by enzyme-linked immunosorbent assay before, and at 3--6 months after castration therapy.RESULTS: VEGF mRNA was down-regulated after castration in benign prostate tissue (P < or = 0.05), whereas in tumour tissue, VEGF levels were reduced in some of the patients but unchanged or increased in others. In most patients whose tumour tissue responded with VEGF reduction, there was a corresponding increase in tumour cell apoptosis. Serum VEGF levels were not significantly changed after castration. Almost all patients responded with a substantial reduction in serum PSA after castration.CONCLUSION: Castration reduces VEGF mRNA expression in benign prostate tissue and generally in those prostate tumours where castration also induces tumour cell apoptosis. This suggests that a therapy-induced down-regulation of VEGF could be important for tumour cell death.
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- Joosen, R.V.L., et al.
(författare)
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Correlating gene expression to physiological parameters and environmental conditions during cold acclimation of Pinus sylvestris, identification of molecular markers using cDNA microarrays
- 2006
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Ingår i: Tree Physiology. - : Oxford University Press (OUP). - 0829-318X .- 1758-4469. ; 26:10, s. 1297-1313
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Tidskriftsartikel (refereegranskat)abstract
- Scots pine (Pinus sylvestris L.) seedlings were grown under different conditions (three field locations, two seasons and two climate room regimes), and then analyzed for freezing tolerance of shoots and roots and for transcript abundance in apical buds based on a cDNA microarray containing about 1500 expressed sequence tags (ESTs) from buds of cold-treated Scots pine seedlings. In a climate room providing long daily photoperiods and high temperatures, seedlings did not develop freezing tolerance, whereas seedlings in a climate room set to provide declining temperatures and day lengths developed moderate freezing tolerance. Control seedlings grown outside under field conditions developed full freezing tolerance. Differences in physiological behavior of the different seedling groups, combined with molecular analysis, allowed identification of a large group of genes, expression of which changed during the development of freezing tolerance. Transcript abundance of several of these genes was highly correlated with freezing tolerance in seedlings differing in provenance, field location or age, making them excellent candidate marker genes for molecular tests for freezing tolerance.
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- Linseisen, J, et al.
(författare)
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Meat consumption in the European Prospective Investigation into Cancer and Nutrition (EPIC) cohorts: results 24-hour dietary recalls
- 2002
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Ingår i: Public Health Nutrition. - 1475-2727. ; 5:6B, s. 1243-1258
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Tidskriftsartikel (refereegranskat)abstract
- Objective: To evaluate meat intake patterns in the European Prospective Investigation into Cancer and Nutrition (EPIC) cohorts. Design and setting: 24-Hour dietary recalls were assessed within the framework of a prospective cohort study in 27 centres across 10 European countries by means of standardised computer-assisted interviews. Subjects: In total, 22 924 women and 13 031 men aged 35-74 years. Results: Mean total meat intake was lowest in the 'health-conscious' cohort in the UK (15 and 21 g day(-1) in women and men, respectively) and highest in the north of Spain, especially in San Sebastian (124 and 234 g day(-1), respectively). In the southern Spanish centres and in Naples (Italy), meat consumption was distinctly lower than in the north of these countries. Central and northern European centres/countries showed rather similar meat consumption patterns, except for the British and French cohorts. Differences in the intake of meat sub-groups (e.g. red meat, processed meat) across EPIC were even higher than found for total meat intake. With a few exceptions, the Mediterranean EPIC centres revealed a higher proportion of beef/veal and poultry and less pork or processed meat than observed in central or northern European centres. The highest sausage consumption was observed for the German EPIC participants, followed by the Norwegians, Swedish, Danish and Dutch. Conclusions: The results demonstrate distinct differences in meat consumption patterns between EPIC centres across Europe. This is an important prerequisite for obtaining further insight into the relationship between meat intake and the development of chronic diseases.
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| 23. |
- Lukanova, Annekatrin, et al.
(författare)
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Body mass index, circulating levels of sex-steroid hormones, IGF-I and IGF-binding protein-3 : a cross-sectional study in healthy women.
- 2004
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Ingår i: European Journal of Endocrinology. - 0804-4643 .- 1479-683X. ; 150:2, s. 161-171
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: Excess weight has been associated with increased risk of cancer at several organ sites. In part, this effect may be modulated through alterations in the metabolism of sex steroids and IGF-I related peptides. The objectives of the study were to examine the association of body mass index (BMI) with circulating androgens (testosterone, androstenedione and dehydroepiandrosterone sulfate (DHEAS)), estrogens (estrone and estradiol), sex hormone-binding globulin (SHBG), IGF-I and IGF-binding protein (IGFBP)-3, and the relationship between sex steroids, IGF-I and IGFBP-3. DESIGN AND METHODS: A cross-sectional analysis was performed using hormonal and questionnaire data of 620 healthy women (177 pre- and 443 post-menopausal). The laboratory measurements of the hormones of interest were available from two previous case-control studies on endogenous hormones and cancer risk. RESULTS: In the pre-menopausal group, BMI was not related to androgens and IGF-I. In the post-menopausal group, estrogens, testosterone and androstenedione increased with increasing BMI. The association with IGF-I was non-linear, with the highest mean concentrations observed in women with BMI between 24 and 25. In both pre- and post-menopausal subjects, IGFBP-3 did not vary across BMI categories and SHBG decreased with increasing BMI. As for the correlations between peptide and steroid hormones, in the post-menopausal group, IGF-I was positively related to androgens, inversely correlated with SHBG, and not correlated with estrogens. In the pre-menopausal group, similar but weaker correlations between IGF-I and androgens were observed. CONCLUSIONS: These observations offer evidence that obesity may influence the levels of endogenous sex-steroid and IGF-related hormones in the circulation, especially after menopause. Circulating IGF-I, androgens and SHBG appear to be related to each other in post-menopausal women.
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| 24. |
- Stattin, Eva-Lena, et al.
(författare)
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SNX10 gene mutation leading to osteopetrosis with dysfunctional osteoclasts
- 2017
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Ingår i: Scientific Reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 7:1
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Tidskriftsartikel (refereegranskat)abstract
- Autosomal recessive osteopetrosis (ARO) is a heterogeneous disorder, characterized by defective osteoclastic resorption of bone that results in increased bone density. We have studied nine individuals with an intermediate form of ARO, from the county of Vasterbotten in Northern Sweden. All afflicted individuals had an onset in early infancy with optic atrophy, and in four patients anemia was present at diagnosis. Tonsillar herniation, foramen magnum stenosis, and severe osteomyelitis of the jaw were common clinical features. Whole exome sequencing, verified by Sanger sequencing, identified a splice site mutation c.212 + 1 G > T in the SNX10 gene encoding sorting nexin 10. Sequence analysis of the SNX10 transcript in patients revealed activation of a cryptic splice site in intron 4 resulting in a frame shift and a premature stop (p.S66Nfs * 15). Haplotype analysis showed that all cases originated from a single mutational event, and the age of the mutation was estimated to be approximately 950 years. Functional analysis of osteoclast progenitors isolated from peripheral blood of patients revealed that stimulation with receptor activator of nuclear factor kappa-B ligand (RANKL) resulted in a robust formation of large, multinucleated osteoclasts which generated sealing zones; however these osteoclasts exhibited defective ruffled borders and were unable to resorb bone in vitro.
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| 25. |
- Travis, R C, et al.
(författare)
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Plasma phyto-oestrogens and prostate cancer in the European prospective investigation into cancer and nutrition
- 2009
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Ingår i: British journal of cancer. - : Springer Science and Business Media LLC. - 1532-1827 .- 0007-0920. ; 100:11, s. 1817-1823
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Tidskriftsartikel (refereegranskat)abstract
- We examined plasma concentrations of phyto-oestrogens in relation to risk for subsequent prostate cancer in a case-control study nested in the European Prospective Investigation into Cancer and Nutrition. Concentrations of isoflavones genistein, daidzein and equol, and that of lignans enterolactone and enterodiol, were measured in plasma samples for 950 prostate cancer cases and 1042 matched control participants. Relative risks (RRs) for prostate cancer in relation to plasma concentrations of these phyto-oestrogens were estimated by conditional logistic regression. Higher plasma concentrations of genistein were associated with lower risk of prostate cancer: RR among men in the highest vs the lowest fifth, 0.71 (95% confidence interval (CI) 0.53-0.96, P trend=0.03). After adjustment for potential confounders this RR was 0.74 (95% CI 0.54-1.00, P trend=0.05). No statistically significant associations were observed for circulating concentrations of daidzein, equol, enterolactone or enterodiol in relation to overall risk for prostate cancer. There was no evidence of heterogeneity in these results by age at blood collection or country of recruitment, nor by cancer stage or grade. These results suggest that higher concentrations of circulating genistein may reduce the risk of prostate cancer but do not support an association with plasma lignans.
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