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Investigator(s) |
Giri VN, Egleston B, Ruth K, Uzzo RG, Chen DY, Buyyounouski M, Raysor S, Hooker S, Torres JB, Ramike T, Mastalski K, Kim TY, Kittles R. Race, Genetic West African Ancestry, and Prostate Cancer Prediction by Prostate-Specific Antigen in Prospectively Screened High-Risk Men. Cancer Prevention Research. 2009 Mar;2(3):244-50.
"Race-specific" prostate-specific antigen (PSA) needs evaluation in men at high risk for prostate cancer for optimizing early detection. Baseline PSA and longitudinal prediction for prostate cancer were examined by self-reported race and genetic West African (WA) ancestry in the Prostate Cancer Risk Assessment Program, a prospective high-risk cohort. Eligibility criteria were age 35 to 69 years, family history of prostate cancer, African American race, or BRCA1/2 mutations. Biopsies were done at low PSA values (<4.0 ng/mL). WA ancestry was discerned by genotyping 100 ancestry informative markers. Cox proportional hazards models evaluated baseline PSA, self-reported race, and genetic WA ancestry. Cox models were used for 3-year predictions for prostate cancer. Six hundred forty-six men (63% African American) were analyzed. Individual WA ancestry estimates varied widely among self-reported African American men. Race-specific differences in baseline PSA were not found by self-reported race or genetic WA ancestry. Among men with >= 1 follow-up visit (405 total, 54% African American), 3-year prediction for prostate cancer with a PSA of 1.5 <4.0 ng/mL was higher in African American men with age in the model (P = 0.025) compared with European American men. Hazard ratios of PSA for prostate cancer were also higher by self-reported race (1.59 for African American versus 1.32 for European American, P = 0.04). There was a trend for increasing prediction for prostate cancer with increasing genetic WA ancestry. "Race-specific" PSA may need to be redefined as higher prediction for prostate cancer at any given PSA in African American men. Large-scale studies are needed to confirm if genetic WA ancestry explains these findings to make progress in personalizing prostate cancer early detection.
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Giri
Uzzo
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Tseng M, Giri V, Bruner DW, Giovannucci E. Prevalence and correlates of vitamin D status in African American men. Bmc Public Health. 2009 Jun;9.
Background: Few studies have examined vitamin D insufficiency in African American men although they are at very high risk. We examined the prevalence and correlates of vitamin D insufficiency among African American men in Philadelphia. Methods: Participants in this cross-sectional analysis were 194 African American men in the Philadelphia region who were enrolled in a risk assessment program for prostate cancer from 10/96-10/07. All participants completed diet and health history questionnaires and provided plasma samples, which were assessed for 25-hydroxyvitamin D (25(OH)D) concentrations. We used linear regression models to examine associations with 25(OH)D concentrations and logistic regression to estimate odds ratios (OR) for having 25(OH)D >= 15 ng/mL. Results: Mean 25(OH)D was 13.7 ng/mL, and 61% of men were classified as having vitamin D insufficiency (25(OH)D <15 ng/mL). Even among men with vitamin D intake >= 400 IU/day, 55% had 25(OH)D concentrations <15 ng/mL. In multivariate models, 25(OH)D concentrations were significantly associated with supplemental vitamin D intake (OR 4.3, 95% confidence interval (CI) 1.5, 12.4) for >400 vs. 0 IU/day), milk consumption (OR 5.9, 95% CI 2.2, 16.0 for >= 3.5 vs. <1 time per week), and blood collection in the summer. Additionally, 25(OH)D concentrations increased with more recreational physical activity (OR 1.3, 95% CI 1.1, 1.6 per hour). A significant inverse association of body mass index with 25(OH)D concentrations in bivariate analyses was attenuated with adjustment for season of blood collection. Conclusion: The problem of low vitamin D status in African American men may be more severe than previously reported. Future efforts to increase vitamin D recommendations and intake, such as through supplementation, are warranted to improve vitamin D status in this particularly vulnerable population.
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Giri
Tseng
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Giri VN, Egleston B, Ruth K, Uzzo RG, Chen DY, Buyyounouski M, Raysor S, Hooker S, Torres JB, Ramike T, Mastalski K, Kim TY, Kittles R. Race, genetic West African ancestry, and prostate cancer prediction by prostate-specific antigen in prospectively screened high-risk men. Cancer Prev Res (Phila Pa). 2009 Mar;2(3):244-50.
"Race-specific" prostate-specific antigen (PSA) needs evaluation in men at high risk for prostate cancer for optimizing early detection. Baseline PSA and longitudinal prediction for prostate cancer were examined by self-reported race and genetic West African (WA) ancestry in the Prostate Cancer Risk Assessment Program, a prospective high-risk cohort. Eligibility criteria were age 35 to 69 years, family history of prostate cancer, African American race, or BRCA1/2 mutations. Biopsies were done at low PSA values (<4.0 ng/mL). WA ancestry was discerned by genotyping 100 ancestry informative markers. Cox proportional hazards models evaluated baseline PSA, self-reported race, and genetic WA ancestry. Cox models were used for 3-year predictions for prostate cancer. Six hundred forty-six men (63% African American) were analyzed. Individual WA ancestry estimates varied widely among self-reported African American men. Race-specific differences in baseline PSA were not found by self-reported race or genetic WA ancestry. Among men with > or =1 follow-up visit (405 total, 54% African American), 3-year prediction for prostate cancer with a PSA of 1.5 to 4.0 ng/mL was higher in African American men with age in the model (P = 0.025) compared with European American men. Hazard ratios of PSA for prostate cancer were also higher by self-reported race (1.59 for African American versus 1.32 for European American, P = 0.04). There was a trend for increasing prediction for prostate cancer with increasing genetic WA ancestry. "Race-specific" PSA may need to be redefined as higher prediction for prostate cancer at any given PSA in African American men. Large-scale studies are needed to confirm if genetic WA ancestry explains these findings to make progress in personalizing prostate cancer early detection.
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Giri
Uzzo
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Tseng M, Giri V, Bruner DW, Giovannucci E. Prevalence and correlates of vitamin D status in African American men. BMC Public Health. 2009;9:191.
BACKGROUND: Few studies have examined vitamin D insufficiency in African American men although they are at very high risk. We examined the prevalence and correlates of vitamin D insufficiency among African American men in Philadelphia. METHODS: Participants in this cross-sectional analysis were 194 African American men in the Philadelphia region who were enrolled in a risk assessment program for prostate cancer from 10/96-10/07. All participants completed diet and health history questionnaires and provided plasma samples, which were assessed for 25-hydroxyvitamin D (25(OH)D) concentrations. We used linear regression models to examine associations with 25(OH)D concentrations and logistic regression to estimate odds ratios (OR) for having 25(OH)D >or= 15 ng/mL. RESULTS: Mean 25(OH)D was 13.7 ng/mL, and 61% of men were classified as having vitamin D insufficiency (25(OH)D <15 ng/mL). Even among men with vitamin D intake >or= 400 IU/day, 55% had 25(OH)D concentrations <15 ng/mL. In multivariate models, 25(OH)D concentrations were significantly associated with supplemental vitamin D intake (OR 4.3, 95% confidence interval (CI) 1.5, 12.4) for >400 vs. 0 IU/day), milk consumption (OR 5.9, 95% CI 2.2, 16.0 for >or= 3.5 vs. <1 time per week), and blood collection in the summer. Additionally, 25(OH)D concentrations increased with more recreational physical activity (OR 1.3, 95% CI 1.1, 1.6 per hour). A significant inverse association of body mass index with 25(OH)D concentrations in bivariate analyses was attenuated with adjustment for season of blood collection. CONCLUSION: The problem of low vitamin D status in African American men may be more severe than previously reported. Future efforts to increase vitamin D recommendations and intake, such as through supplementation, are warranted to improve vitamin D status in this particularly vulnerable population.
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Giri
Tseng
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Giri VN, Coups EJ, Ruth K, Goplerud J, Raysor S, Kim TY, Bagden L, Mastalski K, Zakrzewski D, Leimkuhler S, Watkins-Bruner D. Prostate Cancer Early Detection Program Recruitment Methods and Show Rates in Men at High Risk. J Urol. 2009 Nov;182(5):2212-7.
Purpose: Men with a family history of prostate cancer and black men are at higher risk for prostate cancer. Recruitment and retention of these men at high risk into early detection programs is challenging. We report a comprehensive analysis of recruitment methods, show rates and participant factors from the Prostate Cancer Risk Assessment Program, a prospective, longitudinal prostate cancer screening study. Materials and Methods: Men 35 to 69 years old were eligible for recruitment if they had a family history of prostate cancer, were black or had a BRCA1/2 mutation. Recruitment methods were analyzed using standard statistical methods with respect to participant demographics and presentation to the first program appointment. Results: Of 707 men recruited 64.9% presented to the initial program appointment. More men were recruited via radio than via referral or other methods (chi-square = 298.13, p<0.0001). Men recruited by radio were more likely to be black (p<01.001), less educated (p = 0.003) and not married or partnered (p = 0.007), and have no prostate cancer family history (p <0.001). Men recruited by referral had a higher income (p = 0.007) and were more likely to attend the initial program visit than those recruited by radio or other methods (chi-square = 27.08, p <0.0001). Conclusions: This comprehensive analysis shows that radio led to higher recruitment of black men with lower socioeconomic status. However, these men at high risk have a lower presentation rate for prostate cancer screening. Targeted motivational measures must be studied to improve the show rate for prostate cancer risk assessment in these men at high risk.
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Giri
Coups
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Giri VN, Coups EJ, Ruth K, Goplerud J, Raysor S, Kim TY, Bagden L, Mastalski K, Zakrzewski D, Leimkuhler S, Watkins-Bruner D. Prostate cancer early detection program recruitment methods and show rates in men at high risk. J Urol. 2009 Nov;182(5):2212-7.
PURPOSE: Men with a family history of prostate cancer and black men are at higher risk for prostate cancer. Recruitment and retention of these men at high risk into early detection programs is challenging. We report a comprehensive analysis of recruitment methods, show rates and participant factors from the Prostate Cancer Risk Assessment Program, a prospective, longitudinal prostate cancer screening study. MATERIALS AND METHODS: Men 35 to 69 years old were eligible for recruitment if they had a family history of prostate cancer, were black or had a BRCA1/2 mutation. Recruitment methods were analyzed using standard statistical methods with respect to participant demographics and presentation to the first program appointment. RESULTS: Of 707 men recruited 64.9% presented to the initial program appointment. More men were recruited via radio than via referral or other methods (chi-square = 298.13, p <0.0001). Men recruited by radio were more likely to be black (p <0.001), less educated (p = 0.003) and not married or partnered (p = 0.007), and have no prostate cancer family history (p <0.001). Men recruited by referral had a higher income (p = 0.007) and were more likely to attend the initial program visit than those recruited by radio or other methods (chi-square = 27.08, p <0.0001). CONCLUSIONS: This comprehensive analysis shows that radio led to higher recruitment of black men with lower socioeconomic status. However, these men at high risk have a lower presentation rate for prostate cancer screening. Targeted motivational measures must be studied to improve the show rate for prostate cancer risk assessment in these men at high risk.
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Giri
Coups
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Giri
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Mastalski K, Coups EJ, Ruth K, Raysor S, Giri VN. Substantial Family History of Prostate Cancer in Black Men Recruited for Prostate Cancer Screening Results From the Prostate Cancer Risk Assessment Program. Cancer. 2008 Nov;113(9):2559-64.
BACKGROUND. Black men are at increased risk for prostate cancer (PCA), particularly with a family history (FH) of the disease. Previous reports have raised concern for suboptimal screening of black men with an FH of PCA. The extent of FH of PCA are reported from a prospective, longitudinal PCA screening program for high-risk men. METHODS. Black men ages 35 to 69 years are eligible for PCA screening through the Prostate Cancer Risk Assessment Program (PRAP) regardless of FH. Rates of self-reported FH of PCA, breast, and colon cancer at baseline were compared with an age-matched sample of black men from the 2005 National Health Interview Survey (NHIS) using standard statistical methods. RESULTS. As of January 2007, 332 black men with pedigree information were enrolled in PRAP and FH of PCA was compared with 838 black men from the 2005 NHIS. Black men in PRAP reported significantly more first-degree relatives with PCA compared with black men in the 2005 NHIS (34.3% [95% confidence interval (95% CI), 29.2-39.7] vs 5.7% [95% CI, 3.9-7.4]). Black men in PRAP also had more FH of breast cancer compared with those in the 2005 NHIS (11.5% [95% CI, 8.2-15.4] vs 6.3% [95% CI, 4.6-8.0]). CONCLUSIONS. FH of PCA appears to be a motivating factor for black men seeking PCA screening. Targeted recruitment and education among black families should improve PCA screening rates. Efforts to recruit black men without an FH of PCA are also needed. Cancer 2008;113:2559-64. (C) 2008 American Cancer Society.
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Giri
Coups
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Mastalski K, Coups EJ, Ruth K, Raysor S, Giri VN. Substantial family history of prostate cancer in black men recruited for prostate cancer screening: results from the Prostate Cancer Risk Assessment Program. Cancer. 2008 Nov 1;113(9):2559-64.
BACKGROUND: Black men are at increased risk for prostate cancer (PCA), particularly with a family history (FH) of the disease. Previous reports have raised concern for suboptimal screening of black men with an FH of PCA. The extent of FH of PCA are reported from a prospective, longitudinal PCA screening program for high-risk men. METHODS: Black men ages 35 to 69 years are eligible for PCA screening through the Prostate Cancer Risk Assessment Program (PRAP) regardless of FH. Rates of self-reported FH of PCA, breast, and colon cancer at baseline were compared with an age-matched sample of black men from the 2005 National Health Interview Survey (NHIS) using standard statistical methods. RESULTS: As of January 2007, 332 black men with pedigree information were enrolled in PRAP and FH of PCA was compared with 838 black men from the 2005 NHIS. Black men in PRAP reported significantly more first-degree relatives with PCA compared with black men in the 2005 NHIS (34.3% [95% confidence interval (95% CI), 29.2-39.7] vs 5.7% [95% CI, 3.9-7.4]). Black men in PRAP also had more FH of breast cancer compared with those in the 2005 NHIS (11.5% [95% CI, 8.2-15.4] vs 6.3% [95% CI, 4.6-8.0]). CONCLUSIONS: FH of PCA appears to be a motivating factor for black men seeking PCA screening. Targeted recruitment and education among black families should improve PCA screening rates. Efforts to recruit black men without an FH of PCA are also needed.
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Giri
Coups
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Bryan CJ, Wetmore-Arkader L, Calvano T, Deatrick JA, Giri VN, Bruner DW. Using focus groups to adapt ethnically appropriate, information-seeking and recruitment messages for a prostate cancer screening program for men at high risk. J Natl Med Assoc. 2008 Jun;100(6):674-82.
PURPOSE: To adapt ethnically appropriate radio and newspaper messages in order to increase information-seeking and recruitment to the high-risk Prostate Cancer Risk Assessment Program (PRAP) using input from focus groups. METHODS: We conducted four gender- and ethnic specific-focus groups composed of up to eight participants each. Group participants ranged in age from 35-69 and were either at risk for prostate cancer or were married to someone at risk. Participants evaluated both print and radio advertisements for a PRAP media recruitment campaign, and their recommendations were used to adapt the advertisements. RESULTS: Trigger words, e.g,, "research program," were found to be a particular issue for African-American men who cited concerns about "experimentation," while the other groups cited concerns about time commitments and cost. In the print messages, familial themes garnered an overall favorable response, but Caucasian-American participants responded negatively to the use of photos of age-appropriate models. CONCLUSION: Focus groups are useful in checking health professional assumptions about health messages prior to developing awareness or recruitment advertisements or materials. There was an implied preference for "younger" models among Caucasian Americans. Radio and print messages were adapted using the focus group recommendations, i.e., focusing on familial themes, adding race-specific risk estimates and using younger-than-target group models.
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Giri
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Hwang C, Giri VN, Wilkinson JC, Wright CW, Wilkinson AS, Cooney KA, Duckett CS. EZH2 regulates the transcription of estrogen-responsive genes through association with REA, an estrogen receptor corepressor. Breast Cancer Res Treat. 2008 Jan;107(2):235-42.
Enhancer of zeste homolog 2 (EZH2) is a histone methyltransferase polycomb group (PcG) protein, which has been implicated in the process of cellular differentiation and cancer progression for both breast and prostate cancer. Although transcriptional repression by histone modification appears to contribute to the process of cellular differentiation, it is unclear what mediates the specificity of PcG proteins. Since EZH2 requires a binding partner for its histone methyltransferase activity, we surmised that evaluating interacting proteins might shed light on how the activity of EZH2 is regulated. Here we describe the identification of a novel binding partner of EZH2, the repressor of estrogen receptor activity (REA). REA functions as a transcriptional corepressor of the estrogen receptor and can potentiate the effect of anti-estrogens. REA expression levels have also previously been associated with the degree of differentiation of human breast cancers. We show here that EZH2 can also mediate the repression of estrogen-dependent transcription, and that moreover, the ability of both REA and EZH2 to repress estrogen-dependent transcription are mutually dependent. These data suggest that EZH2 may be recruited to specific target genes by its interaction with the estrogen receptor corepressor REA. The identification of a novel interaction between EZH2 and REA, two transcription factors that have been linked to breast cancer carcinogenesis, may lead to further insights into the process of deregulated gene expression in breast cancer.
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Giri
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Bryan CJ, Wetmore-Arkader L, Calvano T, Deatrick JA, Giri VN, Watkins Bruner D. Using focus groups to adopt ethnically appropriate, information-seeking and recruitment messages for a prostate cancer screening program for men at high risk. J Natl Med Assoc. 2008;100(6):674-82.
Purpose: To adapt ethnically appropriate radio and newspaper messages in order to increase information-seeking and recruitment to the high-risk Prostate Cancer Risk Assessment Program (PRAP) using input from focus groups. Methods: We conducted four gender- and ethnic specific-focus groups composed of up to eight participants each. Group participants ranged in age from 35-69 and were either at risk for prostate cancer or were married to someone at risk. Participants evaluated both print and radio advertisements for a PRAP media recruitment campaign, and their recommendations were used to adapt the advertisements. Results: Trigger words, e.g., "research program," were found to be a particular issue for African-American men who cited concerns about "experimentation," while the other groups cited concerns about time commitments and cost. In the print messages, familial themes garnered an overall favorable response, but Caucasian-American participants responded negatively to the use of photos of age-appropriate models. Conclusion: Focus groups are useful in checking health professional assumptions about health messages prior to developing awareness or recruitment advertisements or materials. There was on implied preference for "younger" models among Caucasian Americans. Radio and print messages were adapted using the focus group recommendations, i.e., focusing on familial themes, adding race-specific risk estimates and using younger-than-target group models. (PsycINFO Database Record (c) 2009 APA, all rights reserved) (journal abstract).
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Giri
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Giri VN, Beebe-Dimmer J, Buyyounouski M, Konski A, Feigenberg SJ, Uzzo RG, Hanks G, Godwin AK, Chen DY, Gordon R, Cescon T, Raysor S, Watkins-Bruner D. Prostate cancer risk assessment program: a 10-year update of cancer detection. J Urol. 2007 Nov;178(5):1920-4; discussion 1924.
PURPOSE: Guidelines for screening men at high risk for prostate cancer remain under investigation. We report our 10-year cancer detection data from the Prostate Cancer Risk Assessment Program, a longitudinal screening program for men at high risk. MATERIALS AND METHODS: Men between ages 35 and 69 years with a family history of prostate cancer, any black man regardless of family history or any patient with a known mutation in the BRCA 1 gene are eligible for the Prostate Cancer Risk Assessment Program and undergo longitudinal followup. Cancer detection, prostate cancer features and the predictive value of screening parameters were determined based on Prostate Cancer Risk Assessment Program biopsy criteria. RESULTS: A total of 609 men were accrued to the Prostate Cancer Risk Assessment Program as of the end of June 2006, of whom 61.2% were black. Of all participants 19% underwent prostate biopsies. The prostate cancer incidence was 9.0%, more than 90% of prostate cancers were Gleason score 6 or higher and 22% were Gleason score 7 or higher. The majority were organ confined. Of men diagnosed with prostate cancer 20% had a prostate specific antigen of less than 2.5 ng/ml and a free prostate specific antigen of less than 25% with a normal digital rectal examination. CONCLUSIONS: Our results support aggressive screening measures for men at high risk for prostate cancer. The majority of cancers detected were at a prostate specific antigen of less than 4.0 ng/ml with a fifth diagnosed at a prostate specific antigen of below 2.5 ng/ml. These cancers were intermediate to high grade and organ confined, indicating a greater likelihood of cure following local therapy in these men.
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Godwin
Giri
Uzzo
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Hwang C, Giri V, Wilkinson J, Wright C, Wilkinson A, Cooney K, Duckett C. EZH2 regulates the transcription of estrogen-responsive genes through association with REA, an estrogen receptor corepressor. Breast Cancer Res Treat. 2007 Apr;:235-42.
Enhancer of zeste homolog 2 (EZH2) is a histone methyltransferase polycomb group (PcG) protein, which has been implicated in the process of cellular differentiation and cancer progression for both breast and prostate cancer. Although transcriptional repression by histone modification appears to contribute to the process of cellular differentiation, it is unclear what mediates the specificity of PcG proteins. Since EZH2 requires a binding partner for its histone methyltransferase activity, we surmised that evaluating interacting proteins might shed light on how the activity of EZH2 is regulated. Here we describe the identification of a novel binding partner of EZH2, the repressor of estrogen receptor activity (REA). REA functions as a transcriptional corepressor of the estrogen receptor and can potentiate the effect of anti-estrogens. REA expression levels have also previously been associated with the degree of differentiation of human breast cancers. We show here that EZH!
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Giri
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Giri
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