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Edward Giovannucci - One of the best experts on this subject based on the ideXlab platform.
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Plasma Antioxidants, Genetic Variation in SOD2, CAT, GPX1, GPX4, and Prostate Cancer Survival
Cancer epidemiology biomarkers & prevention : a publication of the American Association for Cancer Research cosponsored by the American Society of Pre, 2014Co-Authors: Erin L. Van Blarigan, Edward Giovannucci, Meir J Stampfer, Stacey A. Kenfield, Howard D. Sesso, John S. Witte, John W. Erdman, June M. Chan, Kathryn L. PenneyAbstract:Background: Antioxidants may reduce risk of aggressive Prostate Cancer, and single nucleotide polymorphisms (SNPs) in antioxidant genes may modify this association. Methods: We used Cox proportional hazards regression to examine circulating prediagnostic alpha-tocopherol, gamma-tocopherol, and lycopene; SNPs in SOD2 (n=5), CAT (n=6), GPX1 (n=2), GPX4 (n=3); and their interactions and risk of lethal Prostate Cancer among 2,439 men with nonmetastatic Prostate Cancer in the Health Professionals Follow-up Study and Physicians' Health Study. Results: We observed 223 events over a median follow-up of 10 years. Higher alpha-tocopherol levels were associated with lower risk of lethal Prostate Cancer (hazard ratio (HR) 3rd v. 1st quartile (Q): 0.51; 95% confidence interval (CI): 0.30, 0.89; HR 4th v. 1st Q: 0.68; 95% CI: 0.41, 1.13; p-trend: 0.02). Men homozygous for the less common allele (G) at rs3746165 in GPX4 had a 35% lower risk of lethal Prostate Cancer compared to men homozygous for the more common allele (A) (HR: 0.65; 95% CI: 0.43, 0.99). Among men homozygous for the less common allele in rs3746165, high gamma-tocopherol levels were associated with a 3.5-fold increased risk of lethal Prostate Cancer (95% CI: 1.27, 9.72; p-value: 0.02; interaction p-value: 0.01). Conclusions: Among men with nonmetastatic Prostate Cancer, higher circulating prediagnostic alpha-tocopherol may be associated with lower risk of developing lethal disease. Variants in GPX4 may be associated with risk of lethal Prostate Cancer, and may modify the relation between gamma-tocopherol and Prostate Cancer Survival. Impact: Circulating tocopherol levels and variants in GPX4 may affect Prostate Cancer progression.
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abstract lb 28 the igf insulin signaling axis tmprss2 erg and Prostate Cancer Survival
Cancer Research, 2013Co-Authors: Thomas U Ahearn, Andreas Pettersson, Edward C Stack, Travis Gerke, Allison Meisner, Michael Pollak, Stephen Finn, Meir J Stampfer, Massimo Loda, Edward GiovannucciAbstract:Background: One half of Prostate Cancers harbor the TMPRSS2:ERG fusion, a somatic event that may reflect a distinct disease molecular subtype. TMPRSS2 is androgen regulated and ERG is a transcription factor that is part of the ETS family. Based on experimental evidence, we hypothesized that TMPRSS2:ERG tumors would be more sensitive to the insulin like growth factor (IGF)/insulin signaling axis in Prostate Cancer Survival. Methods: We studied participants in the prospective Physicians9 Health Study (PHS) and the Health Professionals Follow-Up Study (HPFS) diagnosed with Prostate Cancer from 1982 - 2005. TMPRSS2:ERG was assessed in tumor tissue microarrays by immunohistochemical evaluation of ERG expression (n=1,236). Pre-diagnostic plasma concentrations of IGF1 (n=307), IGFBP3 (n=307), c-peptide (n=293), and adiponectin (n=120), and tissue expression of the IGF1 receptor (IGF1R; n=713), insulin receptor (IR; n=682), and adionectin receptor (AdipoR2; n=840) were available among men with measured ERG expression. Men have been followed for biochemical recurrence and Cancer mortality through 2012. We used Cox regression to estimate hazard ratios (HRs) and 95% confidence intervals (CI) of associations between circulating biomarkers, TMPRSS2:ERG and Prostate Cancer outcomes. Results: Mean follow-up for lethal Prostate Cancer was 12.8 years and for recurrence 11.1 years. The number of lethal and recurrence events among men with measured blood markers were: IGF1/IGFBP3 25 and 61, c-peptide 20 and 56, and adiponectin 9 and 17, respectively. Among ERG negative tumors, comparing high vs. low concentrations, the multivariable HR for recurrence was 0.4 (95% CI 0.2-1.1) for IGF1, 1.1 (95% CI 0.5-2.8) for IGFBP3, 1.6 (95% CI 0.7-3.6) for c-peptide, and 1.4 (95% CI 0.3-5.6) for adiponectin. The corresponding HRs among ERG positive tumors were 1.8 (95% CI 0.8-4.0; p interaction 0.04) for IGF1, 0.8 (95% CI 0.4-1.8; p interaction 0.61) for IGFBP3, 0.6 (95% CI 0.3-1.3; p interaction 0.16) for c-peptide, and 0.8 (95% CI 0.2-3.6; p interaction 0.53) for adiponectin. Among ERG negative tumors, comparing high vs. low concentrations of the blood markers, the multivariable HR for lethal disease was 0.7 (95% CI 0.2-3.2) for IGF1, 1.4 (95% CI 0.3-5.9) for IGFBP3, 3.64 (95% CI 0.6-20.9) for c-peptide, and 1.1 (95% CI 0.2-7.8) for adiponectin. The corresponding HRs among ERG positive tumors were 2.3 (95% CI 0.5-11.1; p interaction 0.53) for IGF1, 0.6 (95% CI 0.1-2.3; p interaction 0.86) for IGFBP3, 0.7 (95% CI 0.2-2.9; p interaction 0.37) for c-peptide, and 0.4 (95% CI 0.03-5.4; p interaction 0.44) for adiponectin. The expression of IR, IGF1R, and AdipoR2 were significantly (all p-values Conclusions: Although the number of events were relatively small, our results support the hypothesis that TMPRSS2:ERG fusion may modify the association between the IGF/insulin signaling axis and Prostate Cancer prognosis. Citation Format: Thomas U. Ahearn, Andreas Pettersson, Edward C. Stack, Jing Ma, Travis Gerke, Allison Meisner, Michael N. Pollak, Stephen Finn, Meir J. Stampfer, Massimo Loda, Edward L. Giovannucci, Lorelei A. Mucci. The IGF/insulin signaling axis TMPRSS2:ERG and Prostate Cancer Survival. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr LB-28. doi:10.1158/1538-7445.AM2013-LB-28
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Dietary Fatty Acid Intake and Prostate Cancer Survival in Örebro County, Sweden
American journal of epidemiology, 2012Co-Authors: Mara M. Epstein, Julie L. Kasperzyk, Katja Fall, Lorelei A. Mucci, Niclas Håkansson, Alicja Wolk, Swen-olof Andersson, Edward Giovannucci, Alkes L. Price, Ove AndrénAbstract:Although dietary fat has been associated with Prostate Cancer risk, the association between specific fatty acids and Prostate Cancer Survival remains unclear. Dietary intake of 14 fatty acids was analyzed in a population-based cohort of 525 Swedish men with Prostate Cancer in Orebro County (1989-1994). Multivariable hazard ratios and 95% confidence intervals for time to Prostate Cancer death by quartile and per standard deviation increase in intake were estimated by Cox proportional hazards regression. Additional models examined the association by stage at diagnosis (localized: T0-T2/M0; advanced: T0-T4/M1, T3-T4/M0). Among all men, those with the highest omega-3 docosahexaenoic acid and total marine fatty acid intakes were 40% less likely to die from Prostate Cancer (P(trend) = 0.05 and 0.04, respectively). Among men with localized Prostate Cancer, hazard ratios of 2.07 (95% confidence interval: 0.93, 4.59; P(trend) = 0.03) for elevated total fat, 2.39 (95% confidence interval: 1.06, 5.38) for saturated myristic acid, and 2.88 (95% confidence interval: 1.24, 6.67) for shorter chain (C4-C10) fatty acid intakes demonstrated increased risk for disease-specific mortality for the highest quartile compared with the lowest quartile. This study suggests that high intake of total fat and certain saturated fatty acids may worsen Prostate Cancer Survival, particularly among men with localized disease. In contrast, high marine omega-3 fatty acid intake may improve disease-specific Survival for all men.
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smoking and Prostate Cancer Survival and recurrence
JAMA, 2011Co-Authors: Stacey A. Kenfield, Meir J Stampfer, June M. Chan, Edward GiovannucciAbstract:Context Studies of smoking in relation to Prostate Cancer mortality or recurrence in Prostate Cancer patients are limited, with few Prostate Cancer–specific outcomes. Objective To assess the relation of cigarette smoking and smoking cessation with overall, Prostate Cancer–specific, and cardiovascular disease (CVD) mortality and biochemical recurrence among men with Prostate Cancer. Design, Setting, and Participants Prospective observational study of 5366 men diagnosed with Prostate Cancer between 1986 and 2006 in the Health Professionals Follow-Up Study. Main Outcome Measures Hazard ratios (HRs) for overall, Prostate Cancer–specific, and CVD mortality, and biochemical recurrence, defined by an increase in Prostate-specific antigen (PSA) levels. Results There were 1630 deaths, 524 (32%) due to Prostate Cancer and 416 (26%) to CVD, and 878 biochemical recurrences. Absolute crude rates for Prostate Cancer–specific death for never vs current smokers were 9.6 vs 15.3 per 1000 person-years; for all-cause mortality, the corresponding rates were 27.3 and 53.0 per 1000 person-years. In multivariable analysis, current vs never smokers had an increased risk of Prostate Cancer mortality (HR, 1.61; 95% confidence interval [CI], 1.11-2.32), as did current smokers with clinical stage T1 through T3 (HR, 1.80; 95% CI, 1.04-3.12). Current smokers also had increased risk of biochemical recurrence (HR, 1.61; 95% CI, 1.16-2.22), total mortality (HR, 2.28; 95% CI, 1.87-2.80), and CVD mortality (HR, 2.13; 95% CI, 1.39-3.26). After adjusting for clinical stage and grade (likely intermediates of the relation of smoking with Prostate Cancer recurrence and Survival), current smokers had increased risk of Prostate Cancer mortality (HR, 1.38; 95% CI, 0.94-2.03), as did current smokers with clinical stage T1 through T3 (HR, 1.41; 95% CI, 0.80-2.49); they also had an increased risk of biochemical recurrence (HR, 1.47; 95% CI, 1.06-2.04). Greater number of pack-years was associated with significantly increased risk of Prostate Cancer mortality but not biochemical recurrence. Current smokers of 40 or more pack-years vs never smokers had increased Prostate Cancer mortality (HR, 1.82; 95% CI, 1.03-3.20) and biochemical recurrence (HR, 1.48; 95% CI, 0.88-2.48). Compared with current smokers, those who had quit smoking for 10 or more years (HR, 0.60; 95% CI, 0.42-0.87) or who have quit for less than 10 years but smoked less than 20 pack-years (HR, 0.64; 95% CI, 0.28-1.45) had Prostate Cancer mortality risks similar to never smokers (HR, 0.61; 95% CI, 0.42-0.88). Conclusions Smoking at the time of Prostate Cancer diagnosis is associated with increased overall and CVD mortality and Prostate Cancer–specific mortality and recurrence. Men who have quit for at least 10 years have Prostate Cancer–specific mortality risks similar to those who have never smoked.
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Dietary zinc and Prostate Cancer Survival in a Swedish cohort
The American journal of clinical nutrition, 2011Co-Authors: Mara M. Epstein, Julie L. Kasperzyk, Katja Fall, Niclas Håkansson, Alicja Wolk, Jan-erik Johansson, Swen-olof Andersson, Ove Andrén, Edward Giovannucci, Lorelei A. MucciAbstract:Background: Zinc is involved in many essential cellular functions, including DNA repair and immune system maintenance. Although experimental evidence supports a role for zinc in Prostate carcinogenesis, epidemiologic data are inconsistent; no data on Cancer-specific Survival have been reported. Objective: Our objective was to determine whether dietary zinc assessed near the time of Prostate Cancer diagnosis is associated with improved disease-specific Survival. Design: This population-based cohort consists of 525 men aged
Meir J Stampfer - One of the best experts on this subject based on the ideXlab platform.
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dairy intake in relation to Prostate Cancer Survival
International Journal of Cancer, 2017Co-Authors: Lorelei A. Mucci, Mara M. Epstein, Meir J Stampfer, Mary K. Downer, Julie L. Batista, Niclas HåkanssonAbstract:Dairy intake has been associated with increased risk of advanced Prostate Cancer. Two US cohort studies reported increased Prostate Cancer-specific mortality with increased high-fat milk intake. We examined whether dairy and related nutrient intake were associated with Prostate Cancer progression in a Swedish patient population with high dairy consumption. We prospectively followed 525 men with newly diagnosed Prostate Cancer (diagnosed 1989–1994). We identified and confirmed deaths through February 2011 (n = 222 Prostate Cancer-specific, n = 268 from other causes). Cox proportional hazards regression was used to calculate hazard ratios (HR) and 95% confidence intervals (CI) for the associations between food or nutrient intake and Prostate Cancer-specific death. On average, patients consumed 5.0 servings/day of total dairy products at diagnosis. In the whole population, high-fat milk intake was not associated with Prostate Cancer-specific death (95% CI: 0.78, 2.10; p-trend = 0.32; multivariate-adjusted model). However, among patients diagnosed with localized Prostate Cancer, compared to men who consumed <1 servings/day of high-fat milk, those who drank ≥3 servings/day had an increased hazard of Prostate Cancer mortality (HR = 6.10; 95% CI: 2.14, 17.37; p-trend = 0.004; multivariate-adjusted model). Low-fat milk intake was associated with a borderline reduction in Prostate Cancer death among patients with localized Prostate Cancer. These associations were not observed among patients diagnosed with advanced stage Prostate Cancer. Our data suggest a positive association between high-fat milk intake and Prostate Cancer progression among patients diagnosed with localized Prostate Cancer. Further studies are warranted to investigate this association and elucidate the mechanisms by which high-fat milk intake may promote Prostate Cancer progression.
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Dairy intake in relation to Prostate Cancer Survival.
International journal of cancer, 2017Co-Authors: Mary K. Downer, Lorelei A. Mucci, Niclas Håkansson, Alicja Wolk, Jan-erik Johansson, Ove Andrén, Mara M. Epstein, Meir J Stampfer, Julie L. Batista, Katja FallAbstract:Dairy intake has been associated with increased risk of advanced Prostate Cancer. Two US cohort studies reported increased Prostate Cancer-specific mortality with increased high-fat milk intake. We examined whether dairy and related nutrient intake were associated with Prostate Cancer progression in a Swedish patient population with high dairy consumption. We prospectively followed 525 men with newly diagnosed Prostate Cancer (diagnosed 1989–1994). We identified and confirmed deaths through February 2011 (n = 222 Prostate Cancer-specific, n = 268 from other causes). Cox proportional hazards regression was used to calculate hazard ratios (HR) and 95% confidence intervals (CI) for the associations between food or nutrient intake and Prostate Cancer-specific death. On average, patients consumed 5.0 servings/day of total dairy products at diagnosis. In the whole population, high-fat milk intake was not associated with Prostate Cancer-specific death (95% CI: 0.78, 2.10; p-trend = 0.32; multivariate-adjusted model). However, among patients diagnosed with localized Prostate Cancer, compared to men who consumed
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Plasma Antioxidants, Genetic Variation in SOD2, CAT, GPX1, GPX4, and Prostate Cancer Survival
Cancer epidemiology biomarkers & prevention : a publication of the American Association for Cancer Research cosponsored by the American Society of Pre, 2014Co-Authors: Erin L. Van Blarigan, Edward Giovannucci, Meir J Stampfer, Stacey A. Kenfield, Howard D. Sesso, John S. Witte, John W. Erdman, June M. Chan, Kathryn L. PenneyAbstract:Background: Antioxidants may reduce risk of aggressive Prostate Cancer, and single nucleotide polymorphisms (SNPs) in antioxidant genes may modify this association. Methods: We used Cox proportional hazards regression to examine circulating prediagnostic alpha-tocopherol, gamma-tocopherol, and lycopene; SNPs in SOD2 (n=5), CAT (n=6), GPX1 (n=2), GPX4 (n=3); and their interactions and risk of lethal Prostate Cancer among 2,439 men with nonmetastatic Prostate Cancer in the Health Professionals Follow-up Study and Physicians' Health Study. Results: We observed 223 events over a median follow-up of 10 years. Higher alpha-tocopherol levels were associated with lower risk of lethal Prostate Cancer (hazard ratio (HR) 3rd v. 1st quartile (Q): 0.51; 95% confidence interval (CI): 0.30, 0.89; HR 4th v. 1st Q: 0.68; 95% CI: 0.41, 1.13; p-trend: 0.02). Men homozygous for the less common allele (G) at rs3746165 in GPX4 had a 35% lower risk of lethal Prostate Cancer compared to men homozygous for the more common allele (A) (HR: 0.65; 95% CI: 0.43, 0.99). Among men homozygous for the less common allele in rs3746165, high gamma-tocopherol levels were associated with a 3.5-fold increased risk of lethal Prostate Cancer (95% CI: 1.27, 9.72; p-value: 0.02; interaction p-value: 0.01). Conclusions: Among men with nonmetastatic Prostate Cancer, higher circulating prediagnostic alpha-tocopherol may be associated with lower risk of developing lethal disease. Variants in GPX4 may be associated with risk of lethal Prostate Cancer, and may modify the relation between gamma-tocopherol and Prostate Cancer Survival. Impact: Circulating tocopherol levels and variants in GPX4 may affect Prostate Cancer progression.
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abstract lb 28 the igf insulin signaling axis tmprss2 erg and Prostate Cancer Survival
Cancer Research, 2013Co-Authors: Thomas U Ahearn, Andreas Pettersson, Edward C Stack, Travis Gerke, Allison Meisner, Michael Pollak, Stephen Finn, Meir J Stampfer, Massimo Loda, Edward GiovannucciAbstract:Background: One half of Prostate Cancers harbor the TMPRSS2:ERG fusion, a somatic event that may reflect a distinct disease molecular subtype. TMPRSS2 is androgen regulated and ERG is a transcription factor that is part of the ETS family. Based on experimental evidence, we hypothesized that TMPRSS2:ERG tumors would be more sensitive to the insulin like growth factor (IGF)/insulin signaling axis in Prostate Cancer Survival. Methods: We studied participants in the prospective Physicians9 Health Study (PHS) and the Health Professionals Follow-Up Study (HPFS) diagnosed with Prostate Cancer from 1982 - 2005. TMPRSS2:ERG was assessed in tumor tissue microarrays by immunohistochemical evaluation of ERG expression (n=1,236). Pre-diagnostic plasma concentrations of IGF1 (n=307), IGFBP3 (n=307), c-peptide (n=293), and adiponectin (n=120), and tissue expression of the IGF1 receptor (IGF1R; n=713), insulin receptor (IR; n=682), and adionectin receptor (AdipoR2; n=840) were available among men with measured ERG expression. Men have been followed for biochemical recurrence and Cancer mortality through 2012. We used Cox regression to estimate hazard ratios (HRs) and 95% confidence intervals (CI) of associations between circulating biomarkers, TMPRSS2:ERG and Prostate Cancer outcomes. Results: Mean follow-up for lethal Prostate Cancer was 12.8 years and for recurrence 11.1 years. The number of lethal and recurrence events among men with measured blood markers were: IGF1/IGFBP3 25 and 61, c-peptide 20 and 56, and adiponectin 9 and 17, respectively. Among ERG negative tumors, comparing high vs. low concentrations, the multivariable HR for recurrence was 0.4 (95% CI 0.2-1.1) for IGF1, 1.1 (95% CI 0.5-2.8) for IGFBP3, 1.6 (95% CI 0.7-3.6) for c-peptide, and 1.4 (95% CI 0.3-5.6) for adiponectin. The corresponding HRs among ERG positive tumors were 1.8 (95% CI 0.8-4.0; p interaction 0.04) for IGF1, 0.8 (95% CI 0.4-1.8; p interaction 0.61) for IGFBP3, 0.6 (95% CI 0.3-1.3; p interaction 0.16) for c-peptide, and 0.8 (95% CI 0.2-3.6; p interaction 0.53) for adiponectin. Among ERG negative tumors, comparing high vs. low concentrations of the blood markers, the multivariable HR for lethal disease was 0.7 (95% CI 0.2-3.2) for IGF1, 1.4 (95% CI 0.3-5.9) for IGFBP3, 3.64 (95% CI 0.6-20.9) for c-peptide, and 1.1 (95% CI 0.2-7.8) for adiponectin. The corresponding HRs among ERG positive tumors were 2.3 (95% CI 0.5-11.1; p interaction 0.53) for IGF1, 0.6 (95% CI 0.1-2.3; p interaction 0.86) for IGFBP3, 0.7 (95% CI 0.2-2.9; p interaction 0.37) for c-peptide, and 0.4 (95% CI 0.03-5.4; p interaction 0.44) for adiponectin. The expression of IR, IGF1R, and AdipoR2 were significantly (all p-values Conclusions: Although the number of events were relatively small, our results support the hypothesis that TMPRSS2:ERG fusion may modify the association between the IGF/insulin signaling axis and Prostate Cancer prognosis. Citation Format: Thomas U. Ahearn, Andreas Pettersson, Edward C. Stack, Jing Ma, Travis Gerke, Allison Meisner, Michael N. Pollak, Stephen Finn, Meir J. Stampfer, Massimo Loda, Edward L. Giovannucci, Lorelei A. Mucci. The IGF/insulin signaling axis TMPRSS2:ERG and Prostate Cancer Survival. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr LB-28. doi:10.1158/1538-7445.AM2013-LB-28
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Abstract LB-28: The IGF/insulin signaling axis TMPRSS2:ERG and Prostate Cancer Survival.
Epidemiology, 2013Co-Authors: Thomas U Ahearn, Andreas Pettersson, Edward C Stack, Travis Gerke, Allison Meisner, Michael Pollak, Stephen Finn, Meir J Stampfer, Massimo LodaAbstract:Background: One half of Prostate Cancers harbor the TMPRSS2:ERG fusion, a somatic event that may reflect a distinct disease molecular subtype. TMPRSS2 is androgen regulated and ERG is a transcription factor that is part of the ETS family. Based on experimental evidence, we hypothesized that TMPRSS2:ERG tumors would be more sensitive to the insulin like growth factor (IGF)/insulin signaling axis in Prostate Cancer Survival. Methods: We studied participants in the prospective Physicians9 Health Study (PHS) and the Health Professionals Follow-Up Study (HPFS) diagnosed with Prostate Cancer from 1982 - 2005. TMPRSS2:ERG was assessed in tumor tissue microarrays by immunohistochemical evaluation of ERG expression (n=1,236). Pre-diagnostic plasma concentrations of IGF1 (n=307), IGFBP3 (n=307), c-peptide (n=293), and adiponectin (n=120), and tissue expression of the IGF1 receptor (IGF1R; n=713), insulin receptor (IR; n=682), and adionectin receptor (AdipoR2; n=840) were available among men with measured ERG expression. Men have been followed for biochemical recurrence and Cancer mortality through 2012. We used Cox regression to estimate hazard ratios (HRs) and 95% confidence intervals (CI) of associations between circulating biomarkers, TMPRSS2:ERG and Prostate Cancer outcomes. Results: Mean follow-up for lethal Prostate Cancer was 12.8 years and for recurrence 11.1 years. The number of lethal and recurrence events among men with measured blood markers were: IGF1/IGFBP3 25 and 61, c-peptide 20 and 56, and adiponectin 9 and 17, respectively. Among ERG negative tumors, comparing high vs. low concentrations, the multivariable HR for recurrence was 0.4 (95% CI 0.2-1.1) for IGF1, 1.1 (95% CI 0.5-2.8) for IGFBP3, 1.6 (95% CI 0.7-3.6) for c-peptide, and 1.4 (95% CI 0.3-5.6) for adiponectin. The corresponding HRs among ERG positive tumors were 1.8 (95% CI 0.8-4.0; p interaction 0.04) for IGF1, 0.8 (95% CI 0.4-1.8; p interaction 0.61) for IGFBP3, 0.6 (95% CI 0.3-1.3; p interaction 0.16) for c-peptide, and 0.8 (95% CI 0.2-3.6; p interaction 0.53) for adiponectin. Among ERG negative tumors, comparing high vs. low concentrations of the blood markers, the multivariable HR for lethal disease was 0.7 (95% CI 0.2-3.2) for IGF1, 1.4 (95% CI 0.3-5.9) for IGFBP3, 3.64 (95% CI 0.6-20.9) for c-peptide, and 1.1 (95% CI 0.2-7.8) for adiponectin. The corresponding HRs among ERG positive tumors were 2.3 (95% CI 0.5-11.1; p interaction 0.53) for IGF1, 0.6 (95% CI 0.1-2.3; p interaction 0.86) for IGFBP3, 0.7 (95% CI 0.2-2.9; p interaction 0.37) for c-peptide, and 0.4 (95% CI 0.03-5.4; p interaction 0.44) for adiponectin. The expression of IR, IGF1R, and AdipoR2 were significantly (all p-values Conclusions: Although the number of events were relatively small, our results support the hypothesis that TMPRSS2:ERG fusion may modify the association between the IGF/insulin signaling axis and Prostate Cancer prognosis. Citation Format: Thomas U. Ahearn, Andreas Pettersson, Edward C. Stack, Jing Ma, Travis Gerke, Allison Meisner, Michael N. Pollak, Stephen Finn, Meir J. Stampfer, Massimo Loda, Edward L. Giovannucci, Lorelei A. Mucci. The IGF/insulin signaling axis TMPRSS2:ERG and Prostate Cancer Survival. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr LB-28. doi:10.1158/1538-7445.AM2013-LB-28
Massimo Loda - One of the best experts on this subject based on the ideXlab platform.
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abstract lb 28 the igf insulin signaling axis tmprss2 erg and Prostate Cancer Survival
Cancer Research, 2013Co-Authors: Thomas U Ahearn, Andreas Pettersson, Edward C Stack, Travis Gerke, Allison Meisner, Michael Pollak, Stephen Finn, Meir J Stampfer, Massimo Loda, Edward GiovannucciAbstract:Background: One half of Prostate Cancers harbor the TMPRSS2:ERG fusion, a somatic event that may reflect a distinct disease molecular subtype. TMPRSS2 is androgen regulated and ERG is a transcription factor that is part of the ETS family. Based on experimental evidence, we hypothesized that TMPRSS2:ERG tumors would be more sensitive to the insulin like growth factor (IGF)/insulin signaling axis in Prostate Cancer Survival. Methods: We studied participants in the prospective Physicians9 Health Study (PHS) and the Health Professionals Follow-Up Study (HPFS) diagnosed with Prostate Cancer from 1982 - 2005. TMPRSS2:ERG was assessed in tumor tissue microarrays by immunohistochemical evaluation of ERG expression (n=1,236). Pre-diagnostic plasma concentrations of IGF1 (n=307), IGFBP3 (n=307), c-peptide (n=293), and adiponectin (n=120), and tissue expression of the IGF1 receptor (IGF1R; n=713), insulin receptor (IR; n=682), and adionectin receptor (AdipoR2; n=840) were available among men with measured ERG expression. Men have been followed for biochemical recurrence and Cancer mortality through 2012. We used Cox regression to estimate hazard ratios (HRs) and 95% confidence intervals (CI) of associations between circulating biomarkers, TMPRSS2:ERG and Prostate Cancer outcomes. Results: Mean follow-up for lethal Prostate Cancer was 12.8 years and for recurrence 11.1 years. The number of lethal and recurrence events among men with measured blood markers were: IGF1/IGFBP3 25 and 61, c-peptide 20 and 56, and adiponectin 9 and 17, respectively. Among ERG negative tumors, comparing high vs. low concentrations, the multivariable HR for recurrence was 0.4 (95% CI 0.2-1.1) for IGF1, 1.1 (95% CI 0.5-2.8) for IGFBP3, 1.6 (95% CI 0.7-3.6) for c-peptide, and 1.4 (95% CI 0.3-5.6) for adiponectin. The corresponding HRs among ERG positive tumors were 1.8 (95% CI 0.8-4.0; p interaction 0.04) for IGF1, 0.8 (95% CI 0.4-1.8; p interaction 0.61) for IGFBP3, 0.6 (95% CI 0.3-1.3; p interaction 0.16) for c-peptide, and 0.8 (95% CI 0.2-3.6; p interaction 0.53) for adiponectin. Among ERG negative tumors, comparing high vs. low concentrations of the blood markers, the multivariable HR for lethal disease was 0.7 (95% CI 0.2-3.2) for IGF1, 1.4 (95% CI 0.3-5.9) for IGFBP3, 3.64 (95% CI 0.6-20.9) for c-peptide, and 1.1 (95% CI 0.2-7.8) for adiponectin. The corresponding HRs among ERG positive tumors were 2.3 (95% CI 0.5-11.1; p interaction 0.53) for IGF1, 0.6 (95% CI 0.1-2.3; p interaction 0.86) for IGFBP3, 0.7 (95% CI 0.2-2.9; p interaction 0.37) for c-peptide, and 0.4 (95% CI 0.03-5.4; p interaction 0.44) for adiponectin. The expression of IR, IGF1R, and AdipoR2 were significantly (all p-values Conclusions: Although the number of events were relatively small, our results support the hypothesis that TMPRSS2:ERG fusion may modify the association between the IGF/insulin signaling axis and Prostate Cancer prognosis. Citation Format: Thomas U. Ahearn, Andreas Pettersson, Edward C. Stack, Jing Ma, Travis Gerke, Allison Meisner, Michael N. Pollak, Stephen Finn, Meir J. Stampfer, Massimo Loda, Edward L. Giovannucci, Lorelei A. Mucci. The IGF/insulin signaling axis TMPRSS2:ERG and Prostate Cancer Survival. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr LB-28. doi:10.1158/1538-7445.AM2013-LB-28
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Abstract LB-28: The IGF/insulin signaling axis TMPRSS2:ERG and Prostate Cancer Survival.
Epidemiology, 2013Co-Authors: Thomas U Ahearn, Andreas Pettersson, Edward C Stack, Travis Gerke, Allison Meisner, Michael Pollak, Stephen Finn, Meir J Stampfer, Massimo LodaAbstract:Background: One half of Prostate Cancers harbor the TMPRSS2:ERG fusion, a somatic event that may reflect a distinct disease molecular subtype. TMPRSS2 is androgen regulated and ERG is a transcription factor that is part of the ETS family. Based on experimental evidence, we hypothesized that TMPRSS2:ERG tumors would be more sensitive to the insulin like growth factor (IGF)/insulin signaling axis in Prostate Cancer Survival. Methods: We studied participants in the prospective Physicians9 Health Study (PHS) and the Health Professionals Follow-Up Study (HPFS) diagnosed with Prostate Cancer from 1982 - 2005. TMPRSS2:ERG was assessed in tumor tissue microarrays by immunohistochemical evaluation of ERG expression (n=1,236). Pre-diagnostic plasma concentrations of IGF1 (n=307), IGFBP3 (n=307), c-peptide (n=293), and adiponectin (n=120), and tissue expression of the IGF1 receptor (IGF1R; n=713), insulin receptor (IR; n=682), and adionectin receptor (AdipoR2; n=840) were available among men with measured ERG expression. Men have been followed for biochemical recurrence and Cancer mortality through 2012. We used Cox regression to estimate hazard ratios (HRs) and 95% confidence intervals (CI) of associations between circulating biomarkers, TMPRSS2:ERG and Prostate Cancer outcomes. Results: Mean follow-up for lethal Prostate Cancer was 12.8 years and for recurrence 11.1 years. The number of lethal and recurrence events among men with measured blood markers were: IGF1/IGFBP3 25 and 61, c-peptide 20 and 56, and adiponectin 9 and 17, respectively. Among ERG negative tumors, comparing high vs. low concentrations, the multivariable HR for recurrence was 0.4 (95% CI 0.2-1.1) for IGF1, 1.1 (95% CI 0.5-2.8) for IGFBP3, 1.6 (95% CI 0.7-3.6) for c-peptide, and 1.4 (95% CI 0.3-5.6) for adiponectin. The corresponding HRs among ERG positive tumors were 1.8 (95% CI 0.8-4.0; p interaction 0.04) for IGF1, 0.8 (95% CI 0.4-1.8; p interaction 0.61) for IGFBP3, 0.6 (95% CI 0.3-1.3; p interaction 0.16) for c-peptide, and 0.8 (95% CI 0.2-3.6; p interaction 0.53) for adiponectin. Among ERG negative tumors, comparing high vs. low concentrations of the blood markers, the multivariable HR for lethal disease was 0.7 (95% CI 0.2-3.2) for IGF1, 1.4 (95% CI 0.3-5.9) for IGFBP3, 3.64 (95% CI 0.6-20.9) for c-peptide, and 1.1 (95% CI 0.2-7.8) for adiponectin. The corresponding HRs among ERG positive tumors were 2.3 (95% CI 0.5-11.1; p interaction 0.53) for IGF1, 0.6 (95% CI 0.1-2.3; p interaction 0.86) for IGFBP3, 0.7 (95% CI 0.2-2.9; p interaction 0.37) for c-peptide, and 0.4 (95% CI 0.03-5.4; p interaction 0.44) for adiponectin. The expression of IR, IGF1R, and AdipoR2 were significantly (all p-values Conclusions: Although the number of events were relatively small, our results support the hypothesis that TMPRSS2:ERG fusion may modify the association between the IGF/insulin signaling axis and Prostate Cancer prognosis. Citation Format: Thomas U. Ahearn, Andreas Pettersson, Edward C. Stack, Jing Ma, Travis Gerke, Allison Meisner, Michael N. Pollak, Stephen Finn, Meir J. Stampfer, Massimo Loda, Edward L. Giovannucci, Lorelei A. Mucci. The IGF/insulin signaling axis TMPRSS2:ERG and Prostate Cancer Survival. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr LB-28. doi:10.1158/1538-7445.AM2013-LB-28
Thomas U Ahearn - One of the best experts on this subject based on the ideXlab platform.
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abstract lb 28 the igf insulin signaling axis tmprss2 erg and Prostate Cancer Survival
Cancer Research, 2013Co-Authors: Thomas U Ahearn, Andreas Pettersson, Edward C Stack, Travis Gerke, Allison Meisner, Michael Pollak, Stephen Finn, Meir J Stampfer, Massimo Loda, Edward GiovannucciAbstract:Background: One half of Prostate Cancers harbor the TMPRSS2:ERG fusion, a somatic event that may reflect a distinct disease molecular subtype. TMPRSS2 is androgen regulated and ERG is a transcription factor that is part of the ETS family. Based on experimental evidence, we hypothesized that TMPRSS2:ERG tumors would be more sensitive to the insulin like growth factor (IGF)/insulin signaling axis in Prostate Cancer Survival. Methods: We studied participants in the prospective Physicians9 Health Study (PHS) and the Health Professionals Follow-Up Study (HPFS) diagnosed with Prostate Cancer from 1982 - 2005. TMPRSS2:ERG was assessed in tumor tissue microarrays by immunohistochemical evaluation of ERG expression (n=1,236). Pre-diagnostic plasma concentrations of IGF1 (n=307), IGFBP3 (n=307), c-peptide (n=293), and adiponectin (n=120), and tissue expression of the IGF1 receptor (IGF1R; n=713), insulin receptor (IR; n=682), and adionectin receptor (AdipoR2; n=840) were available among men with measured ERG expression. Men have been followed for biochemical recurrence and Cancer mortality through 2012. We used Cox regression to estimate hazard ratios (HRs) and 95% confidence intervals (CI) of associations between circulating biomarkers, TMPRSS2:ERG and Prostate Cancer outcomes. Results: Mean follow-up for lethal Prostate Cancer was 12.8 years and for recurrence 11.1 years. The number of lethal and recurrence events among men with measured blood markers were: IGF1/IGFBP3 25 and 61, c-peptide 20 and 56, and adiponectin 9 and 17, respectively. Among ERG negative tumors, comparing high vs. low concentrations, the multivariable HR for recurrence was 0.4 (95% CI 0.2-1.1) for IGF1, 1.1 (95% CI 0.5-2.8) for IGFBP3, 1.6 (95% CI 0.7-3.6) for c-peptide, and 1.4 (95% CI 0.3-5.6) for adiponectin. The corresponding HRs among ERG positive tumors were 1.8 (95% CI 0.8-4.0; p interaction 0.04) for IGF1, 0.8 (95% CI 0.4-1.8; p interaction 0.61) for IGFBP3, 0.6 (95% CI 0.3-1.3; p interaction 0.16) for c-peptide, and 0.8 (95% CI 0.2-3.6; p interaction 0.53) for adiponectin. Among ERG negative tumors, comparing high vs. low concentrations of the blood markers, the multivariable HR for lethal disease was 0.7 (95% CI 0.2-3.2) for IGF1, 1.4 (95% CI 0.3-5.9) for IGFBP3, 3.64 (95% CI 0.6-20.9) for c-peptide, and 1.1 (95% CI 0.2-7.8) for adiponectin. The corresponding HRs among ERG positive tumors were 2.3 (95% CI 0.5-11.1; p interaction 0.53) for IGF1, 0.6 (95% CI 0.1-2.3; p interaction 0.86) for IGFBP3, 0.7 (95% CI 0.2-2.9; p interaction 0.37) for c-peptide, and 0.4 (95% CI 0.03-5.4; p interaction 0.44) for adiponectin. The expression of IR, IGF1R, and AdipoR2 were significantly (all p-values Conclusions: Although the number of events were relatively small, our results support the hypothesis that TMPRSS2:ERG fusion may modify the association between the IGF/insulin signaling axis and Prostate Cancer prognosis. Citation Format: Thomas U. Ahearn, Andreas Pettersson, Edward C. Stack, Jing Ma, Travis Gerke, Allison Meisner, Michael N. Pollak, Stephen Finn, Meir J. Stampfer, Massimo Loda, Edward L. Giovannucci, Lorelei A. Mucci. The IGF/insulin signaling axis TMPRSS2:ERG and Prostate Cancer Survival. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr LB-28. doi:10.1158/1538-7445.AM2013-LB-28
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Abstract LB-28: The IGF/insulin signaling axis TMPRSS2:ERG and Prostate Cancer Survival.
Epidemiology, 2013Co-Authors: Thomas U Ahearn, Andreas Pettersson, Edward C Stack, Travis Gerke, Allison Meisner, Michael Pollak, Stephen Finn, Meir J Stampfer, Massimo LodaAbstract:Background: One half of Prostate Cancers harbor the TMPRSS2:ERG fusion, a somatic event that may reflect a distinct disease molecular subtype. TMPRSS2 is androgen regulated and ERG is a transcription factor that is part of the ETS family. Based on experimental evidence, we hypothesized that TMPRSS2:ERG tumors would be more sensitive to the insulin like growth factor (IGF)/insulin signaling axis in Prostate Cancer Survival. Methods: We studied participants in the prospective Physicians9 Health Study (PHS) and the Health Professionals Follow-Up Study (HPFS) diagnosed with Prostate Cancer from 1982 - 2005. TMPRSS2:ERG was assessed in tumor tissue microarrays by immunohistochemical evaluation of ERG expression (n=1,236). Pre-diagnostic plasma concentrations of IGF1 (n=307), IGFBP3 (n=307), c-peptide (n=293), and adiponectin (n=120), and tissue expression of the IGF1 receptor (IGF1R; n=713), insulin receptor (IR; n=682), and adionectin receptor (AdipoR2; n=840) were available among men with measured ERG expression. Men have been followed for biochemical recurrence and Cancer mortality through 2012. We used Cox regression to estimate hazard ratios (HRs) and 95% confidence intervals (CI) of associations between circulating biomarkers, TMPRSS2:ERG and Prostate Cancer outcomes. Results: Mean follow-up for lethal Prostate Cancer was 12.8 years and for recurrence 11.1 years. The number of lethal and recurrence events among men with measured blood markers were: IGF1/IGFBP3 25 and 61, c-peptide 20 and 56, and adiponectin 9 and 17, respectively. Among ERG negative tumors, comparing high vs. low concentrations, the multivariable HR for recurrence was 0.4 (95% CI 0.2-1.1) for IGF1, 1.1 (95% CI 0.5-2.8) for IGFBP3, 1.6 (95% CI 0.7-3.6) for c-peptide, and 1.4 (95% CI 0.3-5.6) for adiponectin. The corresponding HRs among ERG positive tumors were 1.8 (95% CI 0.8-4.0; p interaction 0.04) for IGF1, 0.8 (95% CI 0.4-1.8; p interaction 0.61) for IGFBP3, 0.6 (95% CI 0.3-1.3; p interaction 0.16) for c-peptide, and 0.8 (95% CI 0.2-3.6; p interaction 0.53) for adiponectin. Among ERG negative tumors, comparing high vs. low concentrations of the blood markers, the multivariable HR for lethal disease was 0.7 (95% CI 0.2-3.2) for IGF1, 1.4 (95% CI 0.3-5.9) for IGFBP3, 3.64 (95% CI 0.6-20.9) for c-peptide, and 1.1 (95% CI 0.2-7.8) for adiponectin. The corresponding HRs among ERG positive tumors were 2.3 (95% CI 0.5-11.1; p interaction 0.53) for IGF1, 0.6 (95% CI 0.1-2.3; p interaction 0.86) for IGFBP3, 0.7 (95% CI 0.2-2.9; p interaction 0.37) for c-peptide, and 0.4 (95% CI 0.03-5.4; p interaction 0.44) for adiponectin. The expression of IR, IGF1R, and AdipoR2 were significantly (all p-values Conclusions: Although the number of events were relatively small, our results support the hypothesis that TMPRSS2:ERG fusion may modify the association between the IGF/insulin signaling axis and Prostate Cancer prognosis. Citation Format: Thomas U. Ahearn, Andreas Pettersson, Edward C. Stack, Jing Ma, Travis Gerke, Allison Meisner, Michael N. Pollak, Stephen Finn, Meir J. Stampfer, Massimo Loda, Edward L. Giovannucci, Lorelei A. Mucci. The IGF/insulin signaling axis TMPRSS2:ERG and Prostate Cancer Survival. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr LB-28. doi:10.1158/1538-7445.AM2013-LB-28
Anders Bergh - One of the best experts on this subject based on the ideXlab platform.
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tmprss2 erg expression predicts Prostate Cancer Survival and associates with stromal biomarkers
PLOS ONE, 2014Co-Authors: Christina Hagglof, Peter Hammarsten, Kerstin Stromvall, Lars Egevad, Andreas Josefsson, Par Stattin, Torvald Granfors, Anders BerghAbstract:The TMPRSS2-ERG gene fusion is found in approximately half of all Prostate Cancers. The functional and prognostic significance of TMPRSS2-ERG is, however, not fully understood. Based on a historical watchful waiting cohort, an association between TMPRSS2-ERG, evaluated as positive immune staining, and shorter Survival of Prostate Cancer patients was identified. Expression of ERG was also associated with clinical markers such as advanced tumor stage, high Gleason score, presence of metastasis and prognostic tumor cell markers such as high Ki67, pEGFR and pAkt. Novel associations between TMPRSS2-ERG and alterations in the tumor stroma, for example, increased vascular density, hyaluronan and PDGFRβ and decreased Caveolin-1, all known to be associated with an aggressive disease, were found. The present study suggests that the TMPRSS2-ERG fusion gene is associated with a more aggressive Prostate Cancer phenotype, supported by changes in the tumor stroma.
