| 1. |
- Davidsson, Sabina, et al.
(författare)
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CD4 helper T cells, CD8 cytotoxic T cells, and FOXP3(+) regulatory T cells with respect to lethal prostate cancer
- 2013
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Ingår i: Modern Pathology. - : Nature Publishing Group. - 0893-3952 .- 1530-0285. ; 26:3, s. 448-455
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Tidskriftsartikel (refereegranskat)abstract
- Prostate cancer represents a major contributor to cancer mortality, but the majority of men with prostate cancer will die of other causes. Thus, a challenge is identifying potentially lethal disease at diagnosis. Conflicting results have been reported when investigating the relationship between infiltration of lymphocytes and survival in prostate cancer. One of the mechanisms suggested is the recruitment of regulatory T cells (T(regs)), a subpopulation of T cells that have a role in promoting tumor growth. T(regs) counteract tumor rejection through suppressive functions on the anti-immune response but their prognostic significance is still unknown. We report here the results of a conducted case-control study nested in a cohort of men treated with transurethral resection of the prostate and diagnosed incidentally with prostate cancer. Cases are men who died of prostate cancer (n=261) and controls are men who survived >10 years after their diagnosis (n=474). Infiltration of both T(helper) and T(cytotoxic) cells was frequently observed and the majority of the T(regs) were CD4(+). T(helper) or T(cytotoxic) cells were not associated with lethal prostate cancer. However, we found a nearly twofold increased risk of lethal prostate cancer when comparing the highest with the lowest quartile of CD4(+) T(reg) cells (95% confidence interval: 1.3-2.9). Our conclusion is that men with greater numbers of CD4(+) T(regs) in their prostate tumor environment have an increased risk of dying of prostate cancer. Identification of CD4(+) T(regs) in tumor tissue may predict clinically relevant disease at time of diagnosis independently of other clinical factors.Modern Pathology advance online publication, 5 October 2012; doi:10.1038/modpathol.2012.164.
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| 2. |
- Davidsson, Sabina, et al.
(författare)
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Inflammation, Focal Atrophic Lesions, and Prostatic Intraepithelial Neoplasia with Respect to Risk of Lethal Prostate Cancer
- 2011
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Ingår i: Cancer Epidemiology, Biomarkers and Prevention. - : American Association for Cancer Research. - 1055-9965 .- 1538-7755. ; 20:10, s. 2280-2287
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Tidskriftsartikel (refereegranskat)abstract
- Background: A challenge in prostate cancer (PCa) management is identifying potentially lethal disease at diagnosis. Inflammation, focal prostatic atrophy, and prostatic intraepithelial neoplasia (PIN) are common in prostate tumor specimens, but it is not clear whether these lesions have prognostic significance. less thanbrgreater than less thanbrgreater thanMethods: We conducted a case-control study nested in a cohort of men diagnosed with stage T1a-b PCa through transurethral resection of the prostate in Sweden. Cases are men who died of PCa (n = 228). Controls are men who survived more than 10 years after PCa diagnosis without metastases (n = 387). Slides were assessed for Gleason grade, inflammation, PIN, and four subtypes of focal prostatic atrophy: simple atrophy (SA), postatrophic hyperplasia (PAH), simple atrophy with cyst formation, and partial atrophy. We estimated OR and 95% CI for odds of lethal PCa with multivariable logistic regression. less thanbrgreater than less thanbrgreater thanResults: Chronic inflammation and PIN were more frequently observed in tumors with PAH, but not SA. No specific type of atrophy or inflammation was significantly associated with lethal PCa overall, but there was a suggestion of a positive association for chronic inflammation. Independent of age, Gleason score, year of diagnosis, inflammation, and atrophy type, men with PIN were 89% more likely to die of PCa (95% CI: 1.04-3.42). less thanbrgreater than less thanbrgreater thanConclusion: Our data show that PIN, and perhaps presence of moderate or severe chronic inflammation, may have prognostic significance for PCa. less thanbrgreater than less thanbrgreater thanImpact: Lesions in tumor adjacent tissue, and not just the tumor itself, may aid in identification of clinically relevant disease.
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| 3. |
- Epstein, Mara M, et al.
(författare)
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Seasonal variation in expression of markers in the vitamin D pathway in prostate tissue
- 2012
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Ingår i: Cancer Causes and Control. - : Springer. - 0957-5243 .- 1573-7225. ; 23:8, s. 1359-1366
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Tidskriftsartikel (refereegranskat)abstract
- PURPOSE: Recent studies suggest variation in genes along the vitamin D pathway, as well as vitamin D receptor (VDR) protein levels, may be associated with prostate cancer. As serum vitamin D levels vary by season, we sought to determine whether the expression of genes on the vitamin D pathway, assessed in prostate tumor tissue, do the same.METHODS: Our study incorporates mRNA expression data from 362 men in the Swedish Watchful Waiting cohort, diagnosed between 1977 and 1999, and 106 men enrolled in the US Physicians' Health Study (PHS) diagnosed between 1983 and 2004. We also assayed for VDR protein expression among 832 men in the PHS and Health Professionals Follow-up Study cohorts. Season was characterized by date of initial tissue specimen collection categorically and by average monthly ultraviolet radiation levels. One-way analysis of variance was used to examine variation in the expression levels of six genes on the vitamin D pathway-VDR, GC, CYP27A1, CYP27B1, RXRα, CYP24A1-and VDR protein by season, adjusted for age at diagnosis and Gleason grade. Variation was also examined separately among lethal and nonlethal cases.RESULTS: Tumor expression levels of the six genes did not vary significantly by season of tissue collection. No consistent patterns emerged from subgroup analyses by lethal versus nonlethal cases.CONCLUSIONS: Unlike circulating levels of 25(OH) vitamin D, expression levels of genes on the vitamin D pathway and VDR protein did not vary overall by season of tissue collection. Epidemiological analyses of vitamin D gene expression may not be biased by seasonality.
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| 4. |
- Flavin, Richard, et al.
(författare)
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SPINK1 protein expression and prostate cancer progression
- 2014
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Ingår i: Clinical Cancer Research. - Philadelphia, USA : American Association for Cancer Research. - 1078-0432 .- 1557-3265. ; 20:18, s. 4904-11
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Tidskriftsartikel (refereegranskat)abstract
- Purpose: SPINK1 overexpression has been described in prostate cancer and is linked with poor prognosis in many cancers. The objective of this study was to characterize the association between SPINK1 overexpression and prostate cancer-specific survival.Experimental design: The study included 879 participants in the U.S. Physicians' Health Study and Health Professionals Follow-Up Study, diagnosed with prostate cancer (1983-2004) and treated by radical prostatectomy. Protein tumor expression of SPINK1 was evaluated by immunohistochemistry on tumor tissue microarrays.Results: Seventy-four of 879 (8%) prostate cancer tumors were SPINK1 positive. Immunohistochemical data were available for PTEN, p-Akt, pS6, stathmin, androgen receptor (AR), and ERG (as a measure of the TMPRSS2:ERG translocation). Compared with SPINK1-negative tumors, SPINK1-positive tumors showed higher PTEN and stathmin expression, and lower expression of AR (P < 0.01). SPINK1 overexpression was seen in 47 of 427 (11%) ERG-negative samples and in 19 of 427 (4%) ERG-positive cases (P = 0.0003). We found no significant associations between SPINK1 status and Gleason grade or tumor stage. There was no association between SPINK1 expression and biochemical recurrence (P = 0.56). Moreover, there was no association between SPINK1 expression and prostate cancer mortality (there were 75 lethal cases of prostate cancer during a mean of 13.5 years follow-up; HR = 0.71; 95% confidence interval, 0.29-1.76).Conclusions: Our results suggest that SPINK1 protein expression may not be a predictor of recurrence or lethal prostate cancer amongst men treated by radical prostatectomy. SPINK1 and ERG protein expression do not seem to be entirely mutually exclusive, as some previous studies have suggested.
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| 5. |
- Markt, Sarah C., et al.
(författare)
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Genetic Variation Across C-Reactive Protein and Risk of Prostate Cancer
- 2014
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Ingår i: The Prostate. - : Wiley-Blackwell. - 0270-4137 .- 1097-0045. ; 74:10, s. 1034-1042
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND. Inflammation has been hypothesized to play an important etiological role in the initiation or progression of prostate cancer. Circulating levels of the systemic inflammation marker C-reactive protein (CRP) have been associated with increased risk of prostate cancer. We investigated the role of genetic variation in CRP and prostate cancer, under the hypothesis that variants may alter risk of disease.METHODS. We undertook a case-control study nested within the prospective Physicians' Health Study among 1,286 men with incident prostate cancer and 1,264 controls. Four single-nucleotide polymorphisms (SNPs) were selected to capture the common genetic variation across CRP (r(2) > 0.8). We used unconditional logistic regression to assess the association between each SNP and risk of prostate cancer. Linear regression models explored associations between each genotype and plasma CRP levels.RESULTS. None of the CRP SNPs were associated with prostate cancer overall. Individuals with one copy of the minor allele (C) in rs1800947 had an increased risk of high-grade prostate cancer (OR: 1.7; 95% CI: 1.1-2.8), and significantly lower mean CRP levels (P-value < 0.001), however, we found no significant association with lethal disease. Mean CRP levels were significantly elevated in men with one or two copies of the minor allele in rs3093075 and rs1417939, but these were unrelated to prostate cancer risk.CONCLUSION. Our findings suggest that SNPs in the CRP gene are not associated with risk of overall or lethal prostate cancer. Polymorphisms in CRP rs1800947 may be associated with higher grade disease, but our results require replication in other cohorts.
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| 6. |
- Markt, Sarah C., et al.
(författare)
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Sniffing out significant "Pee values" : genome wide association study of asparagus anosmia
- 2016
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Ingår i: BMJ-BRITISH MEDICAL JOURNAL. - London, United Kingdom : B M J Group. - 1756-1833. ; 355
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Tidskriftsartikel (refereegranskat)abstract
- Objective: To determine the inherited factors associated with the ability to smell asparagus metabolites in urine.Design: Genome wide association study.Sstting: Nurses' Health Study and Health Professionals Follow-up Study cohorts.Participants: 6909 men and women of European-American descent with available genetic data from genome wide association studies.Main outcome measure: Participants were characterized as asparagus smellers if they strongly agreed with the prompt "after eating asparagus, you notice a strong characteristic odor in your urine," and anosmic if otherwise. We calculated per-allele estimates of asparagus anosmia for about nine million single nucleotide polymorphisms using logistic regression. P values <5×10(-8) were considered as genome wide significant.Results: 58.0% of men (n=1449/2500) and 61.5% of women (n=2712/4409) had anosmia. 871 single nucleotide polymorphisms reached genome wide significance for asparagus anosmia, all in a region on chromosome 1 (1q44: 248139851-248595299) containing multiple genes in the olfactory receptor 2 (OR2) family. Conditional analyses revealed three independent markers associated with asparagus anosmia: rs13373863, rs71538191, and rs6689553.Conclusion: A large proportion of people have asparagus anosmia. Genetic variation near multiple olfactory receptor genes is associated with the ability of an individual to smell the metabolites of asparagus in urine. Future replication studies are necessary before considering targeted therapies to help anosmic people discover what they are missing.
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| 7. |
- Mucci, Lorelei A., et al.
(författare)
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Circadian dysrhythm and advanced prostate cancer
- 2014
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Ingår i: Journal of Clinical Oncology. - : American Society of Clinical Oncology (ASCO). - 0732-183X .- 1527-7755. ; 32:4
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- Background: The circadian rhythm regulates diverse biologic pathways including tumor oncogenes, metabolism, and cell proliferation. Dysregulation of the circadian rhythm arises from faulty input signals such as exposure to light at night, variability in core circadian rhythm genes, and variation in outputs that regulate circadian behavior including melatonin. There is compelling biologic rationale, but little human data, on circadian dysrhythm and advanced prostate cancer.Methods: We undertook an integrative molecular epidemiology study of circadian dysrhythm and advanced prostate cancer among men in the Icelandic AGES-Reykjavik cohort and the U.S. Health Professionals Follow-up Study, which allowed integration of questionnaire data, biorepositories, and long-term follow-up. We characterized circadian dysrhythm using complimentary approaches: information on sleep problems from questionnaires, prediagnostic melatonin (6-sulfatoxymelatonin) measured on first morning void urine samples, and genetic variation across twelve circadian clock genes. We used multivariable regression models to estimate relative risks (RR) and 95% confidence intervals (CI) of associations with advanced prostate cancer, adjusted for potential confounders.Results: Twenty percent of men reported sleep problems. Men who had trouble falling asleep (RR = 2.1; 95% CI 0.7-6.2) and staying asleep (RR=3.2, 95% CI 1.1-9.7) had an increased risk of developing advanced prostate cancer. Men with sleep problems had significantly lower melatonin levels compared to those without. Low melatonin levels were associated with a statistically significant 4-fold higher risk of advanced prostate cancer compared to those with high levels (95% CI: 1.25-10.0). Variant alleles in two SNPs in cryptochrome (CRY1), involved in generating and maintaining circadian rhythms, were significantly associated with risk of advanced prostate cancer in both cohorts, with a gene-level p-value<0.01.Conclusions: Our results suggest there are multiple nodes in the circadian rhythm that are associated with an increased risk of advanced prostate cancer. As such, there is the potential for complimentary strategies to target circadian disruption and reduce the risk of advanced prostate cancer.
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| 8. |
- Pernar, Claire H., et al.
(författare)
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A Walking Intervention Among Men With Prostate Cancer : A Pilot Study
- 2017
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Ingår i: Clinical Genitourinary Cancer. - New York, USA : Elsevier. - 1558-7673 .- 1938-0682. ; 15:6, s. e1021-e1028
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Tidskriftsartikel (refereegranskat)abstract
- Men diagnosed with prostate cancer have increased risk of disease progression, cardiovascular events, and quality of life impairments. Men with a recent diagnosis randomly assigned to a walking group intervention maintained 10,000 steps per day and experienced improvement in cardiovascular biomarkers compared with usual care. A larger walking group intervention is needed to investigate its potential for improvement in longterm outcomes.BACKGROUND: Men diagnosed with prostate cancer have increased risk for disease progression, cardiovascular events, and impairments in quality of life. This pilot study evaluated the feasibility of a randomized walking group intervention to improve quality of life, circulating biomarkers, and morbidity among men with newly diagnosed prostate cancer.METHODS: Men were recruited at Örebro University Hospital, Sweden, and randomized to an 11-week walking group intervention (n = 21) or usual care (n = 20). The intervention included weekly 1-hour walking group sessions and maintenance of 10,000 steps/day. Outcomes were changes in body composition, clinical factors, biomarkers of cardiovascular health, and quality of life between baseline and end of study. Analysis of covariance was used to compare outcomes in each group adjusted for baseline values.RESULTS: All 41 men randomized completed the 11-week trial. Men assigned to the intervention walked on average 10,644 steps/day, and 92% reported missing 2 or fewer sessions. Both groups experienced similar weight loss at 11 weeks. Men in the intervention had a significant adjusted mean change in high-density lipoprotein of 0.14 mmol/L (95% confidence interval [CI], 0.01-0.27; P = .04), and suggestive adjusted mean changes in low-density lipoprotein of -0.22 mmol/L (95% CI, -0.47 to 0.03; P = .08) and in systolic blood pressure of -8.5 mm Hg (95% CI, -21.2 to 4.2; P = .18), compared with the usual care group.CONCLUSIONS: A walking group intervention among men with recent diagnosis of prostate cancer is feasible and potentially effective in improving cardiovascular health. A larger randomized trial of longer duration is required to elucidate its potential for improvement in longer term outcomes.
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| 9. |
- Pettersson, Andreas, et al.
(författare)
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The ABC model of prostate cancer : A conceptual framework for the design and interpretation of prognostic studies
- 2017
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Ingår i: Cancer. - Hoboken, USA : John Wiley & Sons. - 0008-543X .- 1097-0142. ; 123:9, s. 1490-1496
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Forskningsöversikt (refereegranskat)abstract
- There has been limited success in identifying prognostic biomarkers in prostate cancer. A partial explanation may be that insufficient emphasis has been put on clearly defining what type of marker or patient category a biomarker study aims to identify and how different cohort characteristics affect the ability to identify such a marker. In this article, the authors put forth the ABC model of prostate cancer, which defines 3 groups of patients with localized disease that an investigator may seek to identify: patients who, within a given time frame, will not develop metastases even if untreated (category A), will not develop metastases because of radical treatment (category B), or will develop metastases despite radical treatment (category C). The authors demonstrate that follow-up time and prostate-specific antigen screening intensity influence the prevalence of patients in categories A, B, and C in a study cohort, and that prognostic markers must be tested in both treated and untreated cohorts to accurately distinguish the 3 groups. The authors suggest that more emphasis should be put on considering these factors when planning, conducting, and interpreting the results from prostate cancer biomarker studies, and propose the ABC model as a framework to aid in that process.
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| 10. |
- Sigurdardottir, Lara G., et al.
(författare)
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Circadian disruption, sleep loss, and prostate cancer risk : a systematic review of epidemiologic studies
- 2012
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Ingår i: Cancer Epidemiology, Biomarkers and Prevention. - Philadelphia, USA : American Association for Cancer Research. - 1055-9965 .- 1538-7755. ; 21:7, s. 1002-1011
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Forskningsöversikt (refereegranskat)abstract
- Disruption of the circadian system has been hypothesized to increase cancer risk, either because of direct disruption of the molecular machinery generating circadian rhythms or because of disruption of parameters controlled by the clock such as melatonin levels or sleep duration. This hypothesis has been studied in hormone-dependent cancers among women, but data are sparse about potential effects of circadian disruption on the risk of prostate cancer. This review systematically examines available data evaluating the effects of light at night, sleep patterns, and night shift work on prostate cancer risk.
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