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PROSTATE CANCER DISEASE STAGE COMPARED TO HEALTH AND LIFESTYLE OF MALES IN THE UNITED STATES
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four IL10 SNPs (rs3024496, rs3024509, rs1800896, rs1800872). Also associated with recurrence were one of three SOD2 SNPs (rs5746136: wt/var 1.38 (1.04-1.82), var/var 2.11 (1.26-3.53), p-trend=0.0008), one of 15 NOS2 SNPs (rs10459953: wt/var 1.38 (1.05-1.82), var/var 1.34 (0.85-2.10), p-trend=0.05), two of five CRP SNPs (rs1205: wt/var 0.65 (0.49-0.86), var/var 1.21 (0.76-1.94), p-trend=0.27; rs1800947: wt/var 0.50 (0.33-0.75), p=0.004), one of three IL1RN SNPs (rs878972: wt/ var 0.84 (0.64-1.11), var/var 0.54 (0.31-0.96), p-trend=0.03), one of one IL1B SNP (rs1143627: wt/var 0.80 (0.60-1.06), var/var 0.54 (0.36-0.81), p-trend=0.003), and one of one GSTP1 (rs1695: wt/var 1.40 (1.06-1.86), var/var 1.35 (0.84-2.16), p-trend=0.04). None of two TLR4, two SOD1, three SOD3, five MPO, two HOGG1, two GPX1, eight GSR, four IL6, one IL8, or six NOS3 SNPs was associated with recurrence. CONCLUSIONS: This is the first large study of genetic variation and risk of prostate cancer recurrence nested in a cohort. SNPs in genes involved in the immune response and oxidative stress were associated with risk of prostate cancer recurrence in men surgically treated for clinically localized prostate cancer, independent of known prognostic indicators - pathologic stage and grade. Source of Funding: DOD (DAMD 17-03-0273), NIH/NCI (CA112517), and Prostate Cancer SPORE (P50 CA58236)
468 A GENETIC POLYMORPHISM OF THE OSTEOPROTEGERIN GENE IS ASSOCIATED WITH AN INCREASED RISK OF ADVANCED PROSTATE CANCER Naofumi Narita, Takeshi Yuasa*, Norihiko Tsuchiya, Teruaki Kumazawa, Shintaro Narita, Takamitsu Inoue, Zhiyong Ma, Mitsuru Saito, Yohei Horikawa, Shigeru Satoh, Akita, Japan; Osamu Ogawa, Kyoto, Japan; Tomonori Habuchi, Akita, Japan INTRODUCTION AND OBJECTIVE: Osteoprotegerin (OPG), which acts as an inhibitor of osteoclastogenesis by serving as a decoy receptor for RANKL, is a potent inhibitor of osteoclastic bone resorption and has been investigated as a potential therapeutic modality for the treatment of both osteoporosis and tumour-induced bone disease. Through the inhibition of osteoclast-genesis, OPG also has been suggested to be an important modifier of bone metabolism and bone metastasis. The purpose of this study was to evaluate the role of OPG gene polymorphisms as genetic modifiers in the etiology of prostate cancer and disease progression. METHODS: Three hundred and sixty one patients with prostate cancer and 195 normal controls were enrolled in the study, and two genetic polymorphisms, 149 T/C and 950 T/C in the putative promoter region of OPG, were genotyped. RESULTS: There was no significant difference in the genotype frequencies between prostate cancer patients and controls (P = 0.939 and 0.294 for 149 T/C and 950 T/C polymorphisms, respectively). However, those patients with TC and TT genotypes in the 950 T/C polymorphism had a significantly increased risk of extraprostatic (age-adjusted odds ratio; aOR = 1.74 and 2.03 for TC and TT genotypes compared with the CC genotype, P = 0.028) and metastatic disease (aOR = 1.72 and 2.76 for TC and TT genotypes compared with the CC genotype, P = 0.009) compared with those with the CC genotype. In addition, analysis of the metastatic prostate cancer patients (Stage D) showed that the presence of the T allele of the OPG 950 T/C polymorphism was an independent risk factor predicting survival by Cox proportional hazard regression analyses (P = 0.031). CONCLUSIONS: Progression of prostate cancer may be influenced by an intrinsic genetic factor of the host’s bone metabolism. The variant C allele of 950 T/C in the OPG promoter may play a major role as a genetic safe guard against progression in patients with prostate cancer. Source of Funding: Kobayashi Institute for Innovative Cancer Chemotherapy, the Sagawa Foundation for Promotion of Cancer Research, Grants-in-Aid for Scientific Research from the Ministry of Education, Culture, Sports, Science and Technology, and the GCOE program, Japan
Vol. 181, No. 4, Supplement, Sunday, April 26, 2009
469 PROSTATE CANCER DISEASE STAGE COMPARED TO HEALTH AND LIFESTYLE OF MALES IN THE UNITED STATES Janet L Colli, Michael Knox*, Douglass Clayton, Joshua Waits, Christopher L Amling, Birmingham, AL INTRODUCTION AND OBJECTIVE: Causes for progression of localized prostate cancer (PCa) to advanced stages are largely unknown. PCa incidence data from National Cancer Data Base (NCDB) reveals the variation in newly diagnosed cases of advanced PCa among states. For example, incidence of stage IV PCa in white males diagnosed in 2005 varied from 8% in New Jersey to 18% in Kansas. We do not know whether progression of PCa to a higher stage is related to risk factors or concomitant health conditions. To assess causes of PCa progression, we compare the stage of PCa in newly diagnosed cases to the health and lifestyles of males on a state-by-state basis. METHODS: The percent of stage I, II, III IV, and unclassified PCa diagnosed in white males in 2005 among states were compared to: high cholesterol, obesity; lack of physical activity; diabetes and hypertension for 2003/2005 on a state-by-state basis. To consider access to medical care and socioeconomic status, median family income, urbanization and health insurance status was included in the analysis. Data on the progression of PCa disease in new cases among states were obtained from the NCDB which contains data on 117981 cases of males diagnosed with PCa in 2005. Data on health and lifestyles of males among states were obtained from the Behavoiral Risk Factor Surveillance System, sponsored by the Center for Disease Control and Prevention. Statistical analysis was performed using SPSS version 12.0 software. RESULTS: Advanced PCa correlated inversely with high cholesterol: stage III (R = -0.30, P < 0.05); and stage IV (R = -0.37, P < 0.05). Stage I disease correlated directly with: diabetes (R = 0.44, P < 0.01); hypertension (R = 0.34, P < 0.05), physical inactivity (R = 0.31, P < 0.05) and lack of health insurance (R = 0.31, P < 0.05). CONCLUSIONS: The results of this study suggest that patients with high cholesterol have reduced rates of stage III and IV PCa. These finding are consistent with the hypothesis that statins, which are widely prescribed to reduce high cholesterol, may slow the progression of PCa disease. The results of this study also suggest that stage I PCa is associated with diabetes, hypertension, physical inactivity and lack of health insurance. Source of Funding: None
470 SURGICAL MARGIN STATUS FOR RADICAL PROSTATECTOMY IN PATHOLOGICAL STAGE T2 DISEASE: A POPULATION-BASED STUDY Nathan Lawrentschuk*, Andrew Evans, John Srigley, Joseph L Chin, Bishwajit Bora, Amber Hunter, Robin McLeod, Neil E Fleshner, Toronto, ON, Canada INTRODUCTION AND OBJECTIVE: It is well understood that in the treatment of prostate cancer with surgery, positive surgical margin (PSM) status varies between institutions and there is mounting evidence that high volume surgeons and centres obtain better oncological results. However, larger studies recording PSM for radical prostatectomy are from large centres of excellence and not on a population level. The aim of our study was to establish the province-wide PSM rate for pathological stage T2 disease prostate cancer and assess the overall and regional based PSM rates based on surgical volume. METHODS: A random audit of pathological reports from the Ontario Cancer Registry in Ontario, Canada was analysed for PSM status among patients undergoing radical prostatectomy in 2005 and 2006. Data was collected among 43 hospitals in the province. The sampling consisted of a total of 1577 radical prostatectomies, representing around 60% of the provincial total. Only those with pathological stage T2 were considered as this is a more homogenous group. Regression analysis was performed to assess volume-margin associations. RESULTS: The province-wide surgical PSM rate for pathological stage T2 disease had a median of 33% (mean 33%). Regional rates of
THE JOURNAL OF UROLOGY®
four IL10 SNPs (rs3024496, rs3024509, rs1800896, rs1800872). Also associated with recurrence were one of three SOD2 SNPs (rs5746136: wt/var 1.38 (1.04-1.82), var/var 2.11 (1.26-3.53), p-trend=0.0008), one of 15 NOS2 SNPs (rs10459953: wt/var 1.38 (1.05-1.82), var/var 1.34 (0.85-2.10), p-trend=0.05), two of five CRP SNPs (rs1205: wt/var 0.65 (0.49-0.86), var/var 1.21 (0.76-1.94), p-trend=0.27; rs1800947: wt/var 0.50 (0.33-0.75), p=0.004), one of three IL1RN SNPs (rs878972: wt/ var 0.84 (0.64-1.11), var/var 0.54 (0.31-0.96), p-trend=0.03), one of one IL1B SNP (rs1143627: wt/var 0.80 (0.60-1.06), var/var 0.54 (0.36-0.81), p-trend=0.003), and one of one GSTP1 (rs1695: wt/var 1.40 (1.06-1.86), var/var 1.35 (0.84-2.16), p-trend=0.04). None of two TLR4, two SOD1, three SOD3, five MPO, two HOGG1, two GPX1, eight GSR, four IL6, one IL8, or six NOS3 SNPs was associated with recurrence. CONCLUSIONS: This is the first large study of genetic variation and risk of prostate cancer recurrence nested in a cohort. SNPs in genes involved in the immune response and oxidative stress were associated with risk of prostate cancer recurrence in men surgically treated for clinically localized prostate cancer, independent of known prognostic indicators - pathologic stage and grade. Source of Funding: DOD (DAMD 17-03-0273), NIH/NCI (CA112517), and Prostate Cancer SPORE (P50 CA58236)
468 A GENETIC POLYMORPHISM OF THE OSTEOPROTEGERIN GENE IS ASSOCIATED WITH AN INCREASED RISK OF ADVANCED PROSTATE CANCER Naofumi Narita, Takeshi Yuasa*, Norihiko Tsuchiya, Teruaki Kumazawa, Shintaro Narita, Takamitsu Inoue, Zhiyong Ma, Mitsuru Saito, Yohei Horikawa, Shigeru Satoh, Akita, Japan; Osamu Ogawa, Kyoto, Japan; Tomonori Habuchi, Akita, Japan INTRODUCTION AND OBJECTIVE: Osteoprotegerin (OPG), which acts as an inhibitor of osteoclastogenesis by serving as a decoy receptor for RANKL, is a potent inhibitor of osteoclastic bone resorption and has been investigated as a potential therapeutic modality for the treatment of both osteoporosis and tumour-induced bone disease. Through the inhibition of osteoclast-genesis, OPG also has been suggested to be an important modifier of bone metabolism and bone metastasis. The purpose of this study was to evaluate the role of OPG gene polymorphisms as genetic modifiers in the etiology of prostate cancer and disease progression. METHODS: Three hundred and sixty one patients with prostate cancer and 195 normal controls were enrolled in the study, and two genetic polymorphisms, 149 T/C and 950 T/C in the putative promoter region of OPG, were genotyped. RESULTS: There was no significant difference in the genotype frequencies between prostate cancer patients and controls (P = 0.939 and 0.294 for 149 T/C and 950 T/C polymorphisms, respectively). However, those patients with TC and TT genotypes in the 950 T/C polymorphism had a significantly increased risk of extraprostatic (age-adjusted odds ratio; aOR = 1.74 and 2.03 for TC and TT genotypes compared with the CC genotype, P = 0.028) and metastatic disease (aOR = 1.72 and 2.76 for TC and TT genotypes compared with the CC genotype, P = 0.009) compared with those with the CC genotype. In addition, analysis of the metastatic prostate cancer patients (Stage D) showed that the presence of the T allele of the OPG 950 T/C polymorphism was an independent risk factor predicting survival by Cox proportional hazard regression analyses (P = 0.031). CONCLUSIONS: Progression of prostate cancer may be influenced by an intrinsic genetic factor of the host’s bone metabolism. The variant C allele of 950 T/C in the OPG promoter may play a major role as a genetic safe guard against progression in patients with prostate cancer. Source of Funding: Kobayashi Institute for Innovative Cancer Chemotherapy, the Sagawa Foundation for Promotion of Cancer Research, Grants-in-Aid for Scientific Research from the Ministry of Education, Culture, Sports, Science and Technology, and the GCOE program, Japan
Vol. 181, No. 4, Supplement, Sunday, April 26, 2009
469 PROSTATE CANCER DISEASE STAGE COMPARED TO HEALTH AND LIFESTYLE OF MALES IN THE UNITED STATES Janet L Colli, Michael Knox*, Douglass Clayton, Joshua Waits, Christopher L Amling, Birmingham, AL INTRODUCTION AND OBJECTIVE: Causes for progression of localized prostate cancer (PCa) to advanced stages are largely unknown. PCa incidence data from National Cancer Data Base (NCDB) reveals the variation in newly diagnosed cases of advanced PCa among states. For example, incidence of stage IV PCa in white males diagnosed in 2005 varied from 8% in New Jersey to 18% in Kansas. We do not know whether progression of PCa to a higher stage is related to risk factors or concomitant health conditions. To assess causes of PCa progression, we compare the stage of PCa in newly diagnosed cases to the health and lifestyles of males on a state-by-state basis. METHODS: The percent of stage I, II, III IV, and unclassified PCa diagnosed in white males in 2005 among states were compared to: high cholesterol, obesity; lack of physical activity; diabetes and hypertension for 2003/2005 on a state-by-state basis. To consider access to medical care and socioeconomic status, median family income, urbanization and health insurance status was included in the analysis. Data on the progression of PCa disease in new cases among states were obtained from the NCDB which contains data on 117981 cases of males diagnosed with PCa in 2005. Data on health and lifestyles of males among states were obtained from the Behavoiral Risk Factor Surveillance System, sponsored by the Center for Disease Control and Prevention. Statistical analysis was performed using SPSS version 12.0 software. RESULTS: Advanced PCa correlated inversely with high cholesterol: stage III (R = -0.30, P < 0.05); and stage IV (R = -0.37, P < 0.05). Stage I disease correlated directly with: diabetes (R = 0.44, P < 0.01); hypertension (R = 0.34, P < 0.05), physical inactivity (R = 0.31, P < 0.05) and lack of health insurance (R = 0.31, P < 0.05). CONCLUSIONS: The results of this study suggest that patients with high cholesterol have reduced rates of stage III and IV PCa. These finding are consistent with the hypothesis that statins, which are widely prescribed to reduce high cholesterol, may slow the progression of PCa disease. The results of this study also suggest that stage I PCa is associated with diabetes, hypertension, physical inactivity and lack of health insurance. Source of Funding: None
470 SURGICAL MARGIN STATUS FOR RADICAL PROSTATECTOMY IN PATHOLOGICAL STAGE T2 DISEASE: A POPULATION-BASED STUDY Nathan Lawrentschuk*, Andrew Evans, John Srigley, Joseph L Chin, Bishwajit Bora, Amber Hunter, Robin McLeod, Neil E Fleshner, Toronto, ON, Canada INTRODUCTION AND OBJECTIVE: It is well understood that in the treatment of prostate cancer with surgery, positive surgical margin (PSM) status varies between institutions and there is mounting evidence that high volume surgeons and centres obtain better oncological results. However, larger studies recording PSM for radical prostatectomy are from large centres of excellence and not on a population level. The aim of our study was to establish the province-wide PSM rate for pathological stage T2 disease prostate cancer and assess the overall and regional based PSM rates based on surgical volume. METHODS: A random audit of pathological reports from the Ontario Cancer Registry in Ontario, Canada was analysed for PSM status among patients undergoing radical prostatectomy in 2005 and 2006. Data was collected among 43 hospitals in the province. The sampling consisted of a total of 1577 radical prostatectomies, representing around 60% of the provincial total. Only those with pathological stage T2 were considered as this is a more homogenous group. Regression analysis was performed to assess volume-margin associations. RESULTS: The province-wide surgical PSM rate for pathological stage T2 disease had a median of 33% (mean 33%). Regional rates of