| 1. |
- Andrén, Ove, 1963-, et al.
(författare)
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MUC-1 gene is associated with prostate cancer death : a 20-year follow-up of a population-based study in Sweden
- 2007
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Ingår i: British Journal of Cancer. - London : Harcourt Publishers. - 0007-0920 .- 1532-1827. ; 97:6, s. 730-734
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Tidskriftsartikel (refereegranskat)abstract
- Anti-adhesion mucins have proven to play an important part in the biology of several types of cancer. Therefore, we test the hypothesis that altered expression of MUC-1 is associated with prostate cancer progression. We retrieved archival tumour tissue from a population-based cohort of 195 men with localised prostate cancer (T1a-b, Nx, M0) that has been followed for up to 20 years with watchful waiting. Semi-automated, quantitative immunohistochemistry was undertaken to evaluate MUC-1 expression. We modelled prostate cancer-specific death as a function of MUC-1 levels accounting for age, Gleason grade and tumour extent, and calculated age-adjusted and multivariate adjusted hazard ratios (HR). Men that had tumours with an MUC-intensity lower or higher than normal tissue had a higher risk of dying in prostate cancer, independent of tumour extent and Gleason score (HR 5.1 and 4.5, respectively). Adjustment for Gleason grade and tumour stage did not alter the results. Men with a Gleason score >=7 and MUC-1 deviating from the normal had a 17 (RR=17.1 95% confidence interval=2.3–128) times higher risk to die in prostate cancer compared with men with Gleason score <7 and normal MUC-1 intensity. In summary, our data show that MUC-1 is an independent prognostic marker for prostate cancer death.
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| 2. |
- Setlur, Sunita R., et al.
(författare)
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Estrogen-dependent signaling in a molecularly distinct subclass of aggressive prostate cancer
- 2008
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Ingår i: Journal of the National Cancer Institute. - Oxford : Oxford University Press. - 0027-8874 .- 1460-2105. ; 100:11, s. 815-825
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: The majority of prostate cancers harbor gene fusions of the 5'-untranslated region of the androgen-regulated transmembrane protease serine 2 (TMPRSS2) promoter with erythroblast transformation-specific transcription factor family members. The common fusion between TMPRESS2 and v-ets erythroblastosis virus E26 oncogene homolog (avian) (ERG) is associated with a more aggressive clinical phenotype, implying the existence of a distinct subclass of prostate cancer defined by this fusion. METHODS: We used complementary DNA-mediated annealing, selection, ligation, and extension to determine the expression profiles of 6144 transcriptionally informative genes in archived biopsy samples from 455 prostate cancer patients in the Swedish Watchful Waiting cohort (1987-1999) and the United States-based Physicians(') Health Study cohort (1983-2003). A gene expression signature for prostate cancers with the TMPRSS2-ERG fusion was determined using partitioning and classification models and used in computational functional analysis. Cell proliferation and TMPRSS2-ERG expression in androgen receptor-negative (NCI-H660) prostate cancer cells after treatment with vehicle or estrogenic compounds were assessed by viability assays and quantitative polymerase chain reaction, respectively. All statistical tests were two-sided. RESULTS: We identified an 87-gene expression signature that distinguishes TMPRSS2-ERG fusion prostate cancer as a discrete molecular entity (area under the curve = 0.80, 95% confidence interval [CI] = 0.792 to 0.81; P < .001). Computational analysis suggested that this fusion signature was associated with estrogen receptor (ER) signaling. Viability of NCI-H660 cells decreased after treatment with estrogen (viability normalized to day 0, estrogen vs vehicle at day 8, mean = 2.04 vs 3.40, difference = 1.36, 95% CI = 1.12 to 1.62) or ERbeta agonist (ERbeta agonist vs vehicle at day 8, mean = 1.86 vs 3.40, difference = 1.54, 95% CI = 1.39 to 1.69) but increased after ERalpha agonist treatment (ERalpha agonist vs vehicle at day 8, mean = 4.36 vs 3.40, difference = 0.96, 95% CI = 0.68 to 1.23). Similarly, expression of TMPRSS2-ERG decreased after ERbeta agonist treatment (fold change over internal control, ERbeta agonist vs vehicle at 24 hours, NCI-H660, mean = 0.57- vs 1.0-fold, difference = 0.43-fold, 95% CI = 0.29- to 0.57-fold) and increased after ERalpha agonist treatment (ERalpha agonist vs vehicle at 24 hours, mean = 5.63- vs 1.0-fold, difference = 4.63-fold, 95% CI = 4.34- to 4.92-fold). CONCLUSIONS: TMPRSS2-ERG fusion prostate cancer is a distinct molecular subclass. TMPRSS2-ERG expression is regulated by a novel ER-dependent mechanism.
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| 3. |
- Mucci, Lorelei A., et al.
(författare)
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Nine-gene molecular signature is not associated with prostate cancer death in a watchful waiting cohort
- 2008
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Ingår i: Cancer Epidemiology, Biomarkers and Prevention. - Baltimore : Waverly Press. - 1055-9965 .- 1538-7755. ; 17:1, s. 249-251
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Tidskriftsartikel (refereegranskat)abstract
- Tumor molecular markers hold promise to distinguish potentially lethal from indolent prostate cancer and to guide treatment choices. A previous study identified a nine-gene molecular signature in tumors associated with prostate-specific antigen relapse after prostatectomy. We examined this molecular model in relation to prostate cancer death among 172 men with initially localized disease. We quantified protein expression of the nine genes in tumors to classify progression risk. Accounting for clinical prognostic factors, the nine-gene model did not provide discrimination to predict lethal and indolent prostate cancer.
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| 4. |
- Mucci, Lorelei A., et al.
(författare)
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Testing a multigene signature of prostate cancer death in the Swedish Watchful Waiting Cohort
- 2008
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Ingår i: Cancer Epidemiology, Biomarkers and Prevention. - Philadelphia : American Association for Cancer Research. - 1055-9965 .- 1538-7755. ; 17:7, s. 1682-1688
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Tidskriftsartikel (refereegranskat)abstract
- Although prostate cancer is a leading cause of cancer death, most men die with and not from their disease, underscoring the urgency to distinguish potentially lethal from indolent prostate cancer. We tested the prognostic value of a previously identified multigene signature of prostate cancer progression to predict cancer-specific death. The Örebro Watchful Waiting Cohort included 172 men with localized prostate cancer of whom 40 died of prostate cancer. We quantified protein expression of the markers in tumor tissue by immunohistochemistry and stratified the cohort by quintiles according to risk classification. We accounted for clinical variables (age, Gleason, nuclear grade, and tumor volume) using Cox regression and calculated receiver operator curves to compare discriminatory ability. The hazard ratio of prostate cancer death increased with increasing risk classification by the multigene model, with a 16-fold greater risk comparing highest-risk versus lowest-risk strata, and predicted outcome independent of clinical factors (P = 0.002). The best discrimination came from combining information from the multigene markers and clinical data, which perfectly classified the lowest-risk stratum where no one developed lethal disease; using the two lowest-risk groups as reference, the hazard ratio (95% confidence interval) was 11.3 (4.0-32.8) for the highest-risk group and difference in mortality at 15 years was 60% (50-70%). The combined model provided greater discriminatory ability (area under the curve = 0.78) than the clinical model alone (area under the curve = 0.71; P = 0.04). Molecular tumor markers can add to clinical variables to help distinguish lethal and indolent prostate cancer and hold promise to guide treatment decisions.
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| 5. |
- Rubin, Mark A., et al.
(författare)
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Decreased alpha-methylacyl CoA racemase expression in localized prostate cancer is associated with an increased rate of biochemical recurrence and cancer-specific death
- 2005
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Ingår i: Cancer Epidemiology, Biomarkers and Prevention. - 1055-9965 .- 1538-7755. ; 18, s. 162A-162A
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Tidskriftsartikel (refereegranskat)abstract
- alpha-Methylacyl CoA racemase (AMACR) is overexpressed in prostate cancer relative to benign prostatic tissue. AMACR expression is highest in localized prostate cancer and decreases in metastatic prostate cancer. Herein, we explored the use of AMACR as a biomarker for aggressive prostate cancer. AMACR protein expression was determined by immunohistochemistry using an image analysis system on two localized prostate cancer cohorts consisting of 204 men treated by radical prostatectomy and 188 men followed expectantly. The end points for the cohorts were time to prostate-specific antigen (PSA) failure (i.e., elevation > 0.2 ng/mL) and time to prostate cancer death in the watchful waiting cohort. Using a regression tree method, optimal AMACR protein expression cutpoints were determined to best differentiate prostate cancer outcome in each of the cohorts separately. Cox proportional hazard models were then employed to examine the effect of the AMACR cutpoint on prostate cancer outcome, and adjusted for clinical variables. Lower AMACR tissue expression was associated with worse prostate cancer outcome, independent of clinical variables (hazard ratio, 3.7 for PSA failure; P = 0.018; hazard ratio, 4.1 for prostate cancer death, P = 0.0006). Among those with both low AMACR expression and high Gleason score, the risk of prostate cancer death was 18-fold higher (P = 0.006). The AMACR cutpoint developed using prostate cancer-specific death as the end point predicted PSA failures independent of Gleason score, PSA, and margin status. This is the first study to show that AMACR expression is significantly associated with prostate cancer progression and suggests that not all surrogate end points may be optimal to define biomarkers of aggressive prostate cancer.
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| 6. |
- Stark, Jennifer R., et al.
(författare)
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Prospective study of Trichomonas vaginalis infection and prostate cancer incidence and mortality : Physicians' Health Study
- 2009
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Ingår i: Journal of the National Cancer Institute. - Cary, USA : Oxford University Press. - 0027-8874 .- 1460-2105. ; 101:20, s. 1406-11
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Tidskriftsartikel (refereegranskat)abstract
- Background: A recent nested case-control study found that the presence of antibodies against Trichomonas vaginalis, a common nonviral sexually transmitted infection, was positively associated with subsequent incidence of prostate cancer. We confirmed these findings in an independent population and related serostatus for antibodies against T vaginalis to prostate cancer incidence and mortality.Methods: We conducted a case-control study nested within the Physicians' Health Study that included 673 case subjects with prostate cancer and 673 individually matched control subjects who had available plasma samples. Plasma from blood samples collected at baseline was assayed for antibodies against T vaginalis with an enzyme-linked immunosorbent assay. We used conditional logistic regression to estimate the odds ratios (ORs) of incident prostate cancer, extraprostatic prostate cancer, and cancer that would ultimately progress to bony metastases or prostate cancer-specific death.Results: Although not statistically significant, the magnitude of the association between T vaginalis-seropositive status and overall prostate cancer risk (OR = 1.23, 95% confidence interval [CI] = 0.94 to 1.61) was similar to that reported previously. Furthermore, a seropositive status was associated with statistically significantly increased risks of extraprostatic prostate cancer (OR = 2.17, 95% CI = 1.08 to 4.37) and of cancer that would ultimately progress to bony metastases or prostate cancer-specific death (OR = 2.69, 95% CI = 1.37 to 5.28).Conclusions: This large prospective case-control study obtained further support for an association between a seropositive status for antibodies against T vaginalis and the risk of prostate cancer, with statistically significant associations identified for the risk of extraprostatic prostate cancer and for clinically relevant, potentially lethal prostate cancer.
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| 7. |
- Cnattingius, Sven, et al.
(författare)
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Placental weight and risk of invasive epithelial ovarian cancer with an early age of onset
- 2008
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Ingår i: Cancer Epidemiology, Biomarkers and Prevention. - 1055-9965 .- 1538-7755. ; 17:9, s. 2344-2349
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Tidskriftsartikel (refereegranskat)abstract
- Background: Epithelial ovarian cancer is associated with reproductive factors, but we lack knowledge if hormonal factors during pregnancy influence the mother's risk. Because pregnancy hormones are primarily produced by the placenta, placental weight may be an indirect marker of hormone exposure during pregnancy. Methods: In a nationwide Swedish cohort study, we included women with singleton births from 1982 to 1989. Women were followed for occurrence of invasive epithelial ovarian cancer, death, or emigration through 2004. Hazard ratios (HR) with 95% confidence intervals (95% CI) from Cox models were used to estimate associations between pregnancy exposures and epithelial ovarian cancer. Results: Among 395,171 women with information on placental weight in their first recorded birth, 316 women developed invasive epithelial ovarian cancer. Mean age at diagnosis was 44 years. Compared with women with a placental weight of 500 to 699 g, women with a high (>= 700 g) placental weight had an increased risk of developing epithelial ovarian cancer (HR, 1.47, 95% CI, 1.14-1.90). Compared with women with term pregnancies (40-41 weeks), women with post-term (>= 42 weeks) pregnancies had an increased risk of developing epithelial ovarian cancer (HR, 1.48, 95% CI, 1.00-2.19). These associations were slightly stronger when we included information about women's overall first birth, and slightly weaker when we included information about last recorded birth or ever last birth from 1982 to 1989. Conclusions: Because pregnancy hormone levels increase with placental weight, our study supports the hypothesis that hormone exposures during pregnancy influence the risk of invasive epithelial ovarian cancer among young women.
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| 8. |
- Fall, Katja, 1971-, et al.
(författare)
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Immediate risk for cardiovascular events and suicide following a prostate cancer diagnosis : prospective cohort study
- 2009
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Ingår i: PLoS Medicine. - San Francisco, Calif. : Public Library of Science. - 1549-1277 .- 1549-1676. ; 6:12, s. e1000197-
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Stressful life events have been shown to be associated with altered risk of various health consequences. The aim of the present study was to investigate whether the emotional stress evoked by a prostate cancer diagnosis increases the immediate risks of cardiovascular events and suicide.METHODS AND FINDINGS: We conducted a prospective cohort study by following all men in Sweden who were 30 y or older (n = 4,305,358) for a diagnosis of prostate cancer (n = 168,584) and their subsequent occurrence of cardiovascular events and suicide between January 1, 1961 and December 31, 2004. We used Poisson regression models to calculate relative risks (RRs) and 95% confidence intervals (CIs) of cardiovascular events and suicide among men who had prostate cancer diagnosed within 1 y to men without any cancer diagnosis. The risks of cardiovascular events and suicide were elevated during the first year after prostate cancer diagnosis, particularly during the first week. Before 1987, the RR of fatal cardiovascular events was 11.2 (95% CI 10.4-12.1) during the first week and 1.9 (95% CI 1.9-2.0) during the first year after diagnosis. From 1987, the RR for cardiovascular events, nonfatal and fatal combined, was 2.8 (95% CI 2.5-3.2) during the first week and 1.3 (95% CI 1.3-1.3) during the first year after diagnosis. While the RR of cardiovascular events declined, the RR of suicide was stable over the entire study period: 8.4 (95% CI 1.9-22.7) during the first week and 2.6 (95% CI 2.1-3.0) during the first year after diagnosis. Men 54 y or younger at cancer diagnosis demonstrated the highest RRs of both cardiovascular events and suicide. A limitation of the present study is the lack of tumor stage data, which precluded possibilities of investigating the potential impact of the disease severity on the relationship between a recent diagnosis of prostate cancer and the risks of cardiovascular events and suicide. In addition, we cannot exclude residual confounding as a possible explanation.CONCLUSIONS: Men newly diagnosed with prostate cancer are at increased risks for cardiovascular events and suicide. Future studies with detailed disease characteristic data are warranted.
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| 9. |
- Kasperzyk, Julie L., et al.
(författare)
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One-carbon metabolism-related nutrients and prostate cancer survival
- 2009
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Ingår i: American Journal of Clinical Nutrition. - : Elsevier BV. - 0002-9165 .- 1938-3207. ; 90:3, s. 561-569
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Folate and other one-carbon metabolism nutrients may influence prostate cancer pathogenesis. Prior studies of these nutrients in relation to prostate cancer incidence have been inconclusive, and none have explored prostate cancer survival. OBJECTIVE: The objective was to assess whether dietary intakes of folate, riboflavin, vitamin B-6, vitamin B-12, and methionine measured around the time of prostate cancer diagnosis are associated with prostate cancer survival. DESIGN: This population-based prospective study comprised 525 men from Orebro, Sweden, who received a diagnosis of incident prostate cancer between 1989 and 1994 and completed a self-administered food-frequency questionnaire. Record linkages to the Swedish Death Registry enabled all cases to be followed for up to 20 y after diagnosis, and the cause of death was assigned via medical record review. Cox proportional hazards regression was used to calculate multivariable hazard ratios (HRs) and 95% CIs. During a median of 6.4 y of follow-up, 218 men (42%) died of prostate cancer and 257 (49%) of other causes. RESULTS: A comparison of the highest with the lowest quartile showed that vitamin B-6 intake was inversely associated with prostate cancer-specific death (HR: 0.71; 95% CI: 0.46, 1.10; P for trend = 0.08), especially in men with a diagnosis of localized-stage disease (HR; 0.05; 95% CI: 0.01, 0.26; P for trend = 0.0003). However, vitamin B-6 intake was not associated with improved prostate cancer survival among advanced-stage cases (HR: 1.04; 95% CI: 0.64, 1.72; P for trend = 0.87). Folate, riboflavin, vitamin B-12, and methionine intakes were not associated with prostate cancer survival. CONCLUSION: A high vitamin B-6 intake may improve prostate cancer survival among men with a diagnosis of localized-stage disease.
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| 10. |
- Wilson, Kathryn M., et al.
(författare)
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Acrylamide exposure measured by food frequency questionnaire and hemoglobin adduct levels and prostate cancer risk in the Cancer of the Prostate in Sweden Study
- 2009
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Ingår i: International Journal of Cancer. - : WILEY-LISS. - 0020-7136 .- 1097-0215. ; 124:10, s. 2384-2390
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Tidskriftsartikel (refereegranskat)abstract
- Acrylamide, a probable human carcinogen, is formed during the cooking of many commonly consumed foods. Data are scant on whether dietary acrylamide represents an important cancer risk in humans. We studied the association between acrylamide and prostate cancer risk using 2 measures of acrylamide exposure: intake from a food frequency questionnaire (FFQ) and acrylamide adducts to hemoglobin. We also studied the correlation between these 2 exposure measures. We used data from the population-based case-control study Cancer of the Prostate in Sweden (CAPS). Dietary data was available for 1,499 cases and 1, 118 controls. Hemoglobin adducts of acrylamide were measured in blood samples from a subset of 170 cases and 161 controls. We calculated odds ratios (ORs) for the risk of prostate cancer in high versus low quantiles of acrylamide exposure using logistic regression. The correlation between FFQ acrylamide intake and acrylamide adducts in non-smokers was 0.25 (95% confidence interval: 0.14-0.35), adjusted for age, region, energy intake, and laboratory batch. Among controls the correlation was 0.35 (95% CI: 0.21-0.48); among cases it was 0.15 (95% CI: 0.00-0.30). The OR of prostate cancer for the highest versus lowest quartile of acrylamide adducts was 0.93 (95% CI: 0.47-1.85, p-value for trend = 0.98). For FFQ acrylamide, the OR of prostate cancer for the highest versus lowest quintile was 0.97 (95% CI: 0.75-1.27,p trend = 0.67). No significant associations were found between acrylamide exposure and risk of prostate cancer by stage, grade, or PSA level. Acrylamide adducts to hemoglobin and FFQ-measured acrylamide intake were moderately correlated. Neither measure of acrylamide exposure-hemoglobin adducts or FFQ-was associated with risk of prostate cancer. (C) 2008 Wiley-Liss. Inc.
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