- Email: [email protected]
121 RISK OF PROSTATE CANCER FOLLOWING PRESCRIPTION TESTOSTERONE USE
Vol. 183, No. 4, Supplement, Sunday, May 30, 2010
119 DESCRIPTIVE EPIDEMIOLOGY OF UROLOGIC PAIN SYMPTOMS IN MEN AND WOMEN Jessica Brewer*, Carol Link, Watertown, MA; Paul Eggers, John Kusek, Bethesda, MD; John McKinlay, Watertown, MA INTRODUCTION AND OBJECTIVES: It is commonly assumed that most non-malignant urologic conditions worsen as individuals age. However, data from cross-sectional studies indicate that the prevalence of chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) and interstitial cystitis/painful bladder syndrome (IC/PBS) is lower with advancing age. We examined the epidemiology of symptoms suggestive of IC/PBS and CP/CPPS in a longitudinal study. METHODS: Analyses were performed using baseline and follow-up data from a population-based survey which used a stratified 2-stage cluster design to sample adults aged 30-79 years. This analysis reports on data from 3407 participants (1268 men and 2139 women; 1102 Black, 1083 Hispanic, and 1222 White) with both baseline and follow-up data. The average number of years between baseline and follow-up was 4.7. Symptoms suggestive of IC/PBS were defined as pain increasing as the bladder fills and/or pain relieved by urination (fairly often, usually, almost always) for at least 3 months. Symptoms suggestive of CP/CPPS were defined as perineal and/or ejaculatory pain and a Chronic Prostatitis Symptom Index pain score of 4⫹. We present prevalence, remission, and incidence of IC/PCS and CP/CPPS over the 4.7 y period. RESULTS: Baseline Mean age of men and women reporting symptoms of IC/PBS and CP/CPPS was 53.8 and 44.8 years respectively. Overall, 3.9% of men (n⫽62) reported symptoms of CP/CPPS at baseline. 80.1% of those men did not report these symptoms at follow-up. Baseline prevalence of symptoms of IC/PBS was 1.2% in men (n⫽23) and 2.5% in women (n⫽80). At follow-up, 84.3% of those men and 88.2% of those women did not report symptoms. Estimates of incidence of symptoms characteristic of both conditions were: CP/ CPPS 1.1%, and IC/PBS 0.9% in men and 1.3% in women. CONCLUSIONS: Symptoms suggestive of CP/CPPS and IC/ PBS are not reported in over three-fourths of the sample after a period of nearly five years. Identification of factors that may promote remission of symptoms need to be examined. Source of Funding: Award Number U01DK056842 from the National Institute of Diabetes And Digestive And Kidney Diseases (NIDDK). The content is solely the responsibility of the authors and does not necessarily represent the official views of NIDDK.
120 LONG-TERM IMPACT OF ARSENIC IN DRINKING WATER ON BLADDER CANCER MORTALITY AND HEALTH CARE TWENTY YEARS AFTER END OF EXPOSURE Jose Francisco Lopez, Mario Ferna´ndez*, Matias Westendarp, Bruno Vivaldi, Luis Fernando Coz, Santiago, Chile INTRODUCTION AND OBJECTIVES: Exposure to arsenic in drinking water is a well-known risk factor for bladder cancer. Moreover, bladder tumors from arsenic-exposed patients may behave more aggresively and result in increased mortality. The aim of this study was to assess bladder cancer health care and mortality trends during the last decades in a well-studied arsenic-exposed area in northern Chile. METHODS: Between 1955 and 1989, approximately 400.000 inhabitants of the II Region in northern Chile were exposed to arsenic in drinking water, containing levels up to seventeen times over the international recommendation. Arsenic levels for the last 60 years were obtained and correlated with bladder cancer mortality and hospital admissions rates during this period. Mortality rate trends were estimated using Poisson regression analysis for men and women separately, comparing the affected region with the rest of the country using rate ratios. RESULTS: Arsenic concentrations in drinking water were normalized in 1989 after over three decades of elevated levels, decreasing
THE JOURNAL OF UROLOGY姞
e49
gradually from 569 ug/L in 1955 to 43 ug/L in 1989. Mortality rates increased with a clear latency pattern between 15 and 25 years after high exposure commenced, from 3 and 2 per 100.000 in 1955 to 6 and 6 per 100.000 in 1977 for men and women respectively. There was a trend towards increase during the analyzed period, reaching peak mortality rates of 22 per 100.000 in men and 18 per 100.000 in women during the last ten years. Poisson regression models showed evident trends of increased rate ratios in the studied region compared to the rest of the country until present time for men (peak RR 3.7; 95% CI ⫽ 2.5; 5.5) and women (peak RR 5.7; 95% CI ⫽ 3.2; 10.2). Moreover, age at time of cancer-specific death was significantly lower in the exposed region (mean age 69.6; 95% CI ⫽ 68.4; 70.7 versus mean age 73.7; 95% CI ⫽ 73.3; 74.2; p⬍0.01). Bladder cancer hospital admissions were also significantly higher in the affected region than in the rest of the country during the last two decades ( peak RR 3.6; 95% CI ⫽ 3.0; 4.7). CONCLUSIONS: Exposure to arsenic is related to high mortality rates and a significant need for bladder cancer health care even twenty years after controlling arsenic levels in drinking water. The affected population should be informed and local authorities should be aware of the significant impact of this ecologic factor. Early detection programs and an adequate access to health care services should be warranted. Finally, further research is required to identify strategies for management of bladder cancer in arsenic-exposed populations. Source of Funding: None
Prostate Cancer: Epidemiology and Natural History I Podium 6 Sunday, May 30, 2010
8:00 AM-10:00 AM
121 RISK OF PROSTATE CANCER FOLLOWING PRESCRIPTION TESTOSTERONE USE Stephen Van Den Eeden*, Jun Shan, Charles Quesenberry, Laurel Habel, Oakland, CA INTRODUCTION AND OBJECTIVES: Long-term unintended outcomes related to use of testosterone are unknown. There is particular concern that such use may increase the risk of subsequently developing prostate cancer. We sought to estimate the risk of prostate cancer associated with medically prescribed testosterone using electronic health records. METHODS: The study setting was Kaiser Permanente Northern California (KPNC), a large integrated health delivery system that serves over 3.2 million individuals. Data were available from electronic records for the KPNC Cancer Registry, all inpatient and outpatient encounters, and pharmacy prescriptions. All men diagnosed with prostate cancer in KPNC between 2000 and 2007 were identified from the KPNC Cancer Registry (n⫽19,472). Three controls per case were matched on race/ethnicity, age, residence, and KPNC service facility and membership (n⫽58,411). Electronic diagnostic data were searched for evidence of hypogonadism while the pharmacy database was examined for records of testosterone prescriptions. Logistic regression analyses were conducted to estimate the odds ratio (OR) and 95% confidence interval (95% CI) of developing prostate cancer after a diagnosis of hypogonadism and/or use of exogenous testosterone. RESULTS: Less than one percent of cases or controls received a prescription for testosterone or had a hypogonadism diagnosis. After adjustment for matching factors and race/ethnicity, we found no association between hypogonadism and prostate cancer (OR 1.18, 95% CI 0.88-1.59). Use of exogenous testosterone was associated with an inverse association with prostate cancer (OR 0.80, 95% CI 0.66-0.97). When we examined the duration of testosterone use we observed no evidence of a duration effect.
e50
THE JOURNAL OF UROLOGY姞
Vol. 183, No. 4, Supplement, Sunday, May 30, 2010
CONCLUSIONS: Prescription testosterone use was not associated with an increased risk of prostate cancer among this large and diverse population.
Source of Funding: Supported in part by the Urological Research Foundation, Prostate SPORE grant (P50 CA9038605S2) and the Robert H. Lurie Comprehensive Cancer Center grant (P30 CA60553)
Source of Funding: Kaiser Permanente
122 NEW RISK ALLELES IN PATIENTS WITH FAMILIAL AND NON-FAMILIAL PROSTATE CANCER Joshua J. Meeks*, Matthias D. Hofer, Brian T. Helfand, Chicago, IL; Stacy Loeb, Baltimore, MD; Jessica A. Banks, Donghui Kan, William J. Catalona, Chicago, IL INTRODUCTION AND OBJECTIVES: Genome-wide association analyses of men with prostate cancer (PCa) have identified multiple independent chromosomal loci associated with PCa susceptibility. Yet, the relationship of these alleles to PCa risk in men with a positive family history is controversial; some studies demonstrate an association with family history of PCa, while others have not shown this relationship. We therefore sought to compare the frequency of risk alleles with the presence of a family history of PCa. METHODS: 596 Caucasian men underwent radical retropubic prostatectomy by a single surgeon. All patients had genotype information for 14 single nucleotide polymorphisms (SNPs) along 2p15, 3q21, 5p15, 8q24, 10q11, 11q13, 17q12, 17q24, 19q13, and Xp11. A positive family history of PCa was defined by an affected first-degree relative. Carrier status was defined using a best-fit genetic model. Statistical analysis was used to compare the allele frequencies and carrier status between men with a positive family history of PCa and those without a family history of PCa. RESULTS: Overall, 31.5% of patients reported a first-degree family history of PCa. Men who reported a family history of PCa also had a significantly (p⬍0.05) higher allele frequency of the SNPs rs2710646 (2p15), rs16901979 (8q24), and rs1447295 (8q24), compared to those without a family history. For the 8q24 risk alleles, men with a family history of PCa also had a significantly higher carrier frequency of the rs16901979 and rs1447295 risk alleles compared to men without a family history. Specifically, there were almost twice as many carriers of the SNP rs16901979 with a family history compared to those without a family history (15.3% vs. 8.4%, p⫽0.015). CONCLUSIONS: In our patient cohort, men with a firstdegree relative affected with PCa were more likely to be carriers of the 8q24 and 2p15 risk alleles than those without an affected firstdegree relative. These results confirm that at least two genetic loci identified through genome-wide association are also prevalent in men with a family history of PCa and may contribute to their risk of developing PCa.
123 GENETIC VARIANTS SIGNIFICANTLY IMPROVE DETECTION OF PROSTATE CANCER AND ARE ASSOCIATED WITH AGGRESSIVE FEATURES IN PATIENTS WITH A “NORMAL” PSA AND DRE Brian T. Helfand*, Chicago, IL; Stacy Loeb, Baltimore, MD; Matthias D. Hofer, Ronald Kim, Phillip R. Cooper, Donghui Kan, William J. Catalona, Chicago, IL INTRODUCTION AND OBJECTIVES: Several reports suggest that a combination of genetic prostate cancer (CaP) susceptibility variants may independently predict CaP risk and tumor features. However, the ability to detect CaP in patients with a “normal” PSA and non-suspicious digital rectal examination (DRE) remains to be determined. Therefore, the present study examined the performance of genetic variants in prediction models for CaP risk and aggressiveness. METHODS: From June 2002-May 2008, we examined 79 Caucasian men with clinical stage T1c prostate cancer diagnosed at a PSA ⬍4.0 ng/mL and 595 controls with negative DRE and PSA ⬍4.0 ng/mL. The genotypes for 14 CaP risk alleles (on chromosomes 2p15, 3q21, 5p15, 8q24, 10q11, 11q13, 17q12, 17q24, 19q13, and Xp11) were compared between CaP cases and controls. Additional analyses were used to compare the pathologic features between carriers and noncarriers of the variants. RESULTS: 12 of the variants were over-represented in CaP patients with “normal” PSA values compared to controls. Among Caucasian men with “normal” PSA values, carriers of an increasing number of genetic variants were at a significantly increased risk of CaP (ptrend⬍0.001). Men with ⱖ9 genetic variants had an OR of 6.7 (95% CI 2.0-23.7) compared to men with ⱕ4 variants (Table 1). On multivariate analysis with age, the genetic variants remained significant predictors of CaP risk in this population (OR 2.3, 95% CI 1.5-3.8, p⫽0.0005). There also was an increase in the frequency of high Gleason grade (ⱖ7) disease in carriers of 11 variants. Specifically, a statistically significant difference was observed for the frequency of both highgrade cancer (p⫽0.03) and seminal vesicle invasion (p⫽0.02) in carriers of the 8q24 rs16901979 variant. CONCLUSIONS: A substantial proportion of biopsy-detectable CaP occurs in men with PSA levels ⬎4 ng/mL and negative DRE. In this population, genetic risk variants are significantly associated with CaP risk and may guide in the prediction of aggressive disease. Future studies are warranted to determine the utility of incorporating genetic risk alleles into CaP screening programs. Table 1. Cumulative Model Comparing Frequency of Genetic Variants in Patients with “Normal” PSA and DRE Carrier of Case Control OR Variants # N⫽ (%) N⫽ (%) (95% C.I.) p-value 0-4 9 (11.4) 145 (24.4) — — 5
19 (24.0)
158 (26.5)
1.9 (0.8-4.4)
0.12
6
14 (17.8)
129 (21.7)
1.7 (0.7-4.2)
0.21
7
19 (24.0)
108 (18.2)
2.8 (1.2-6.5)
0.14
8
13 (16.5)
43 (7.2)
4.9 (2.0-12.2)
0.0007
5 (6.3)
12 (2.0)
6.7 (1.9-23.2)
0.0026
ⱖ9
Source of Funding: Supported in part by the Urological Research Foundation, Prostate SPORE grant (P50 CA9038605S2) and the Robert H. Lurie Comprehensive Cancer Center grant (P30 CA60553)
119 DESCRIPTIVE EPIDEMIOLOGY OF UROLOGIC PAIN SYMPTOMS IN MEN AND WOMEN Jessica Brewer*, Carol Link, Watertown, MA; Paul Eggers, John Kusek, Bethesda, MD; John McKinlay, Watertown, MA INTRODUCTION AND OBJECTIVES: It is commonly assumed that most non-malignant urologic conditions worsen as individuals age. However, data from cross-sectional studies indicate that the prevalence of chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) and interstitial cystitis/painful bladder syndrome (IC/PBS) is lower with advancing age. We examined the epidemiology of symptoms suggestive of IC/PBS and CP/CPPS in a longitudinal study. METHODS: Analyses were performed using baseline and follow-up data from a population-based survey which used a stratified 2-stage cluster design to sample adults aged 30-79 years. This analysis reports on data from 3407 participants (1268 men and 2139 women; 1102 Black, 1083 Hispanic, and 1222 White) with both baseline and follow-up data. The average number of years between baseline and follow-up was 4.7. Symptoms suggestive of IC/PBS were defined as pain increasing as the bladder fills and/or pain relieved by urination (fairly often, usually, almost always) for at least 3 months. Symptoms suggestive of CP/CPPS were defined as perineal and/or ejaculatory pain and a Chronic Prostatitis Symptom Index pain score of 4⫹. We present prevalence, remission, and incidence of IC/PCS and CP/CPPS over the 4.7 y period. RESULTS: Baseline Mean age of men and women reporting symptoms of IC/PBS and CP/CPPS was 53.8 and 44.8 years respectively. Overall, 3.9% of men (n⫽62) reported symptoms of CP/CPPS at baseline. 80.1% of those men did not report these symptoms at follow-up. Baseline prevalence of symptoms of IC/PBS was 1.2% in men (n⫽23) and 2.5% in women (n⫽80). At follow-up, 84.3% of those men and 88.2% of those women did not report symptoms. Estimates of incidence of symptoms characteristic of both conditions were: CP/ CPPS 1.1%, and IC/PBS 0.9% in men and 1.3% in women. CONCLUSIONS: Symptoms suggestive of CP/CPPS and IC/ PBS are not reported in over three-fourths of the sample after a period of nearly five years. Identification of factors that may promote remission of symptoms need to be examined. Source of Funding: Award Number U01DK056842 from the National Institute of Diabetes And Digestive And Kidney Diseases (NIDDK). The content is solely the responsibility of the authors and does not necessarily represent the official views of NIDDK.
120 LONG-TERM IMPACT OF ARSENIC IN DRINKING WATER ON BLADDER CANCER MORTALITY AND HEALTH CARE TWENTY YEARS AFTER END OF EXPOSURE Jose Francisco Lopez, Mario Ferna´ndez*, Matias Westendarp, Bruno Vivaldi, Luis Fernando Coz, Santiago, Chile INTRODUCTION AND OBJECTIVES: Exposure to arsenic in drinking water is a well-known risk factor for bladder cancer. Moreover, bladder tumors from arsenic-exposed patients may behave more aggresively and result in increased mortality. The aim of this study was to assess bladder cancer health care and mortality trends during the last decades in a well-studied arsenic-exposed area in northern Chile. METHODS: Between 1955 and 1989, approximately 400.000 inhabitants of the II Region in northern Chile were exposed to arsenic in drinking water, containing levels up to seventeen times over the international recommendation. Arsenic levels for the last 60 years were obtained and correlated with bladder cancer mortality and hospital admissions rates during this period. Mortality rate trends were estimated using Poisson regression analysis for men and women separately, comparing the affected region with the rest of the country using rate ratios. RESULTS: Arsenic concentrations in drinking water were normalized in 1989 after over three decades of elevated levels, decreasing
THE JOURNAL OF UROLOGY姞
e49
gradually from 569 ug/L in 1955 to 43 ug/L in 1989. Mortality rates increased with a clear latency pattern between 15 and 25 years after high exposure commenced, from 3 and 2 per 100.000 in 1955 to 6 and 6 per 100.000 in 1977 for men and women respectively. There was a trend towards increase during the analyzed period, reaching peak mortality rates of 22 per 100.000 in men and 18 per 100.000 in women during the last ten years. Poisson regression models showed evident trends of increased rate ratios in the studied region compared to the rest of the country until present time for men (peak RR 3.7; 95% CI ⫽ 2.5; 5.5) and women (peak RR 5.7; 95% CI ⫽ 3.2; 10.2). Moreover, age at time of cancer-specific death was significantly lower in the exposed region (mean age 69.6; 95% CI ⫽ 68.4; 70.7 versus mean age 73.7; 95% CI ⫽ 73.3; 74.2; p⬍0.01). Bladder cancer hospital admissions were also significantly higher in the affected region than in the rest of the country during the last two decades ( peak RR 3.6; 95% CI ⫽ 3.0; 4.7). CONCLUSIONS: Exposure to arsenic is related to high mortality rates and a significant need for bladder cancer health care even twenty years after controlling arsenic levels in drinking water. The affected population should be informed and local authorities should be aware of the significant impact of this ecologic factor. Early detection programs and an adequate access to health care services should be warranted. Finally, further research is required to identify strategies for management of bladder cancer in arsenic-exposed populations. Source of Funding: None
Prostate Cancer: Epidemiology and Natural History I Podium 6 Sunday, May 30, 2010
8:00 AM-10:00 AM
121 RISK OF PROSTATE CANCER FOLLOWING PRESCRIPTION TESTOSTERONE USE Stephen Van Den Eeden*, Jun Shan, Charles Quesenberry, Laurel Habel, Oakland, CA INTRODUCTION AND OBJECTIVES: Long-term unintended outcomes related to use of testosterone are unknown. There is particular concern that such use may increase the risk of subsequently developing prostate cancer. We sought to estimate the risk of prostate cancer associated with medically prescribed testosterone using electronic health records. METHODS: The study setting was Kaiser Permanente Northern California (KPNC), a large integrated health delivery system that serves over 3.2 million individuals. Data were available from electronic records for the KPNC Cancer Registry, all inpatient and outpatient encounters, and pharmacy prescriptions. All men diagnosed with prostate cancer in KPNC between 2000 and 2007 were identified from the KPNC Cancer Registry (n⫽19,472). Three controls per case were matched on race/ethnicity, age, residence, and KPNC service facility and membership (n⫽58,411). Electronic diagnostic data were searched for evidence of hypogonadism while the pharmacy database was examined for records of testosterone prescriptions. Logistic regression analyses were conducted to estimate the odds ratio (OR) and 95% confidence interval (95% CI) of developing prostate cancer after a diagnosis of hypogonadism and/or use of exogenous testosterone. RESULTS: Less than one percent of cases or controls received a prescription for testosterone or had a hypogonadism diagnosis. After adjustment for matching factors and race/ethnicity, we found no association between hypogonadism and prostate cancer (OR 1.18, 95% CI 0.88-1.59). Use of exogenous testosterone was associated with an inverse association with prostate cancer (OR 0.80, 95% CI 0.66-0.97). When we examined the duration of testosterone use we observed no evidence of a duration effect.
e50
THE JOURNAL OF UROLOGY姞
Vol. 183, No. 4, Supplement, Sunday, May 30, 2010
CONCLUSIONS: Prescription testosterone use was not associated with an increased risk of prostate cancer among this large and diverse population.
Source of Funding: Supported in part by the Urological Research Foundation, Prostate SPORE grant (P50 CA9038605S2) and the Robert H. Lurie Comprehensive Cancer Center grant (P30 CA60553)
Source of Funding: Kaiser Permanente
122 NEW RISK ALLELES IN PATIENTS WITH FAMILIAL AND NON-FAMILIAL PROSTATE CANCER Joshua J. Meeks*, Matthias D. Hofer, Brian T. Helfand, Chicago, IL; Stacy Loeb, Baltimore, MD; Jessica A. Banks, Donghui Kan, William J. Catalona, Chicago, IL INTRODUCTION AND OBJECTIVES: Genome-wide association analyses of men with prostate cancer (PCa) have identified multiple independent chromosomal loci associated with PCa susceptibility. Yet, the relationship of these alleles to PCa risk in men with a positive family history is controversial; some studies demonstrate an association with family history of PCa, while others have not shown this relationship. We therefore sought to compare the frequency of risk alleles with the presence of a family history of PCa. METHODS: 596 Caucasian men underwent radical retropubic prostatectomy by a single surgeon. All patients had genotype information for 14 single nucleotide polymorphisms (SNPs) along 2p15, 3q21, 5p15, 8q24, 10q11, 11q13, 17q12, 17q24, 19q13, and Xp11. A positive family history of PCa was defined by an affected first-degree relative. Carrier status was defined using a best-fit genetic model. Statistical analysis was used to compare the allele frequencies and carrier status between men with a positive family history of PCa and those without a family history of PCa. RESULTS: Overall, 31.5% of patients reported a first-degree family history of PCa. Men who reported a family history of PCa also had a significantly (p⬍0.05) higher allele frequency of the SNPs rs2710646 (2p15), rs16901979 (8q24), and rs1447295 (8q24), compared to those without a family history. For the 8q24 risk alleles, men with a family history of PCa also had a significantly higher carrier frequency of the rs16901979 and rs1447295 risk alleles compared to men without a family history. Specifically, there were almost twice as many carriers of the SNP rs16901979 with a family history compared to those without a family history (15.3% vs. 8.4%, p⫽0.015). CONCLUSIONS: In our patient cohort, men with a firstdegree relative affected with PCa were more likely to be carriers of the 8q24 and 2p15 risk alleles than those without an affected firstdegree relative. These results confirm that at least two genetic loci identified through genome-wide association are also prevalent in men with a family history of PCa and may contribute to their risk of developing PCa.
123 GENETIC VARIANTS SIGNIFICANTLY IMPROVE DETECTION OF PROSTATE CANCER AND ARE ASSOCIATED WITH AGGRESSIVE FEATURES IN PATIENTS WITH A “NORMAL” PSA AND DRE Brian T. Helfand*, Chicago, IL; Stacy Loeb, Baltimore, MD; Matthias D. Hofer, Ronald Kim, Phillip R. Cooper, Donghui Kan, William J. Catalona, Chicago, IL INTRODUCTION AND OBJECTIVES: Several reports suggest that a combination of genetic prostate cancer (CaP) susceptibility variants may independently predict CaP risk and tumor features. However, the ability to detect CaP in patients with a “normal” PSA and non-suspicious digital rectal examination (DRE) remains to be determined. Therefore, the present study examined the performance of genetic variants in prediction models for CaP risk and aggressiveness. METHODS: From June 2002-May 2008, we examined 79 Caucasian men with clinical stage T1c prostate cancer diagnosed at a PSA ⬍4.0 ng/mL and 595 controls with negative DRE and PSA ⬍4.0 ng/mL. The genotypes for 14 CaP risk alleles (on chromosomes 2p15, 3q21, 5p15, 8q24, 10q11, 11q13, 17q12, 17q24, 19q13, and Xp11) were compared between CaP cases and controls. Additional analyses were used to compare the pathologic features between carriers and noncarriers of the variants. RESULTS: 12 of the variants were over-represented in CaP patients with “normal” PSA values compared to controls. Among Caucasian men with “normal” PSA values, carriers of an increasing number of genetic variants were at a significantly increased risk of CaP (ptrend⬍0.001). Men with ⱖ9 genetic variants had an OR of 6.7 (95% CI 2.0-23.7) compared to men with ⱕ4 variants (Table 1). On multivariate analysis with age, the genetic variants remained significant predictors of CaP risk in this population (OR 2.3, 95% CI 1.5-3.8, p⫽0.0005). There also was an increase in the frequency of high Gleason grade (ⱖ7) disease in carriers of 11 variants. Specifically, a statistically significant difference was observed for the frequency of both highgrade cancer (p⫽0.03) and seminal vesicle invasion (p⫽0.02) in carriers of the 8q24 rs16901979 variant. CONCLUSIONS: A substantial proportion of biopsy-detectable CaP occurs in men with PSA levels ⬎4 ng/mL and negative DRE. In this population, genetic risk variants are significantly associated with CaP risk and may guide in the prediction of aggressive disease. Future studies are warranted to determine the utility of incorporating genetic risk alleles into CaP screening programs. Table 1. Cumulative Model Comparing Frequency of Genetic Variants in Patients with “Normal” PSA and DRE Carrier of Case Control OR Variants # N⫽ (%) N⫽ (%) (95% C.I.) p-value 0-4 9 (11.4) 145 (24.4) — — 5
19 (24.0)
158 (26.5)
1.9 (0.8-4.4)
0.12
6
14 (17.8)
129 (21.7)
1.7 (0.7-4.2)
0.21
7
19 (24.0)
108 (18.2)
2.8 (1.2-6.5)
0.14
8
13 (16.5)
43 (7.2)
4.9 (2.0-12.2)
0.0007
5 (6.3)
12 (2.0)
6.7 (1.9-23.2)
0.0026
ⱖ9
Source of Funding: Supported in part by the Urological Research Foundation, Prostate SPORE grant (P50 CA9038605S2) and the Robert H. Lurie Comprehensive Cancer Center grant (P30 CA60553)