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Lower urinary tract reconstruction might be required to create a safe reservoir for urinary drainage before renal transplantation. We report the successful creation of a tension-free donor ureteral-ileocecal pouch anastomosis in a left-sided transplantation of a donor kidney, which necessitated tunneling the donor ureter through the mesentery of the sigmoid colon.

Background: Genome-wide association studies have identified more than eighty risk variants for prostate cancer, mainly in European or Asian populations. The generalizability of these variants in other racial/ethnic populations needs to be understood before the loci can be utilized widely in risk modeling. Methods: We examined 82 previously reported risk variants in 5,096 prostate cancer cases and 4,972 controls of African ancestry. Association testing was performed using logistic regression adjusted for age, study and global ancestry. Cumulative effects were assessed through a multi-SNP genetic risk score. Results: Among the 82 known risk alleles, 68 (83%) were positively associated with prostate cancer risk in men of African ancestry and 30 (37%) were minimally replicated at p Conclusions: The consistent directions of effect for the vast majority of variants in men of African ancestry indicate common functional alleles that are shared across populations. Some variants that failed to replicate may not be the best markers of prostate cancer risk for men of African ancestry, and thus further exploration of these loci through sequencing and fine-mapping is needed. Citation Format: Ying Han, Lisa B. Signorello, Sara S. Strom, Rick A. Kittles, Benjamin A. Rybicki, Janet L. Stanford, Phyllis J. Goodman, Sonja I. Berndt, John Carpten, Graham Casey, Lisa Chu, David V. Conti, Kristin A. Rand, Ryan Diver, Anselm JM Hennis, Esther M. John, Adam S. Kibel, Eric A. Klein, Suzanne Kolb, Loic Le Marchand, M Cristina Leske, Adam B. Murphy, Christine Neslund-Dudas, Jong Y. Park, Curtis A. Pettaway, Timothy R. Rebbeck, Susan M. Gapstur, Siqun Lilly Zheng, Suh-Yuh Wu, John S. Witte, Jianfeng Xu, William B. Isaacs, Sue A. Ingles, Ann W. Hsing, The PRACTICAL Consortium, The ELLIPSE GAME-ON Consortium, Douglas F. Easton, Rosalind A. Eeles, Fredrick R. Schumacher, Stephen J. Chanock, Barbara Nemesure, William J. Blot, Daniel O. Stram, Brian E. Henderson, Christopher A. Haiman. Generalizability of established prostate cancer risk variants in men of African ancestry. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 5066. doi:10.1158/1538-7445.AM2014-5066

An article in The Journal of Urology addresses a frustrating feature of PSA-based prostate cancer screening, namely the fact that PSA is a fairly nonspecific marker for cancer. The authors provide a potential diagnostic test for the most common non-cancer diagnosis on prostate biopsy—asymptomatic inflammatory prostatitis (AIP)—and recommend its use as a means of avoiding unnecessary prostate biopsies.

Introduction: Prostate cancer (PCa) is increasing among HIV-infected (HIV+) men who are living longer on effective anti-retroviral therapy (ART). African-American (AA) men are overrepresented in the HIV+ population and are at high risk for PCa and PCa-related health disparities. Little is known about PCa presentation and treatment utilization in HIV+ and HIV+AA men. Methods: We conducted a retrospective analysis of HIV+ men with PCa seen at Northwestern Medicine in Chicago, IL, from 2001 to 2012. Cases identified through electronic medical record billing, encounter, and procedure codes were verified by chart review. We collected data on age, race/ethnicity, ART, CD4+ cell counts, and covariates for HIV and PCa. Descriptive and comparative statistical analyses were used. Results: We studied 44 HIV+ men with a median age of 59.5 years at PCa diagnosis. There were 15 (34%) AAs, 25 (57%) Caucasians (CAs), two (5%) Hispanics, and two (5%) of unknown/other ethnicity. The majority (42/44 [95%]) were on ART with a median CD4+ cell count at PCa diagnosis of 372/μl (88-1215, ± 306). Median prostate specific antigen (PSA) at PCa diagnosis was 5.2 ng/ml (0.1-547, ± 102), and PSA did not differ between AAs and CAs (p=.83). Of the 34 men with clinical staging, 20 (59%) were cT1c, 11 (32%) cT2a, one (3%) cT2c, and two (6%) cT3 or higher. Stage at presentation was similar among AAs and CAs. Of all men with clinically localized (CL) disease in whom initial treatment was known, the majority (14/27 [52%]) underwent radical prostatectomy (RP) with most (9/14 [64%]) utilizing the robotic approach. Rates of RP in AAs and CAs were comparable (4/10 [40%] vs 9/15 [60%], p = 0.47). Radiation (including external beam (5, [19%]) and brachytherapy (2, [7%])) was used as primary therapy in seven (26%) men. Six (22%) elected watchful waiting/active surveillance. Overall, received treatments adhered to National Comprehensive Cancer Network recommendations for risk-appropriate therapy in 91% of men, with no disparities found between AAs and CAs (13/13 [100%] vs 15/17 [88%], p=.20). Conclusions: HIV+ men are younger at PCa diagnosis compared to the general population (median age at diagnosis=67) and are likely to present with CL-PCa, regardless of race. Utilization of RP for CL-PCa and rates of overall appropriateness of therapy in HIV+ and HIV+ AAs are high and comparable to national data, suggesting no major treatment disparities based on HIV and racial status exist. Further studies on etiologies of early PCa presentation and RP- and cancer-related outcomes in HIV+ men are needed. Citation Format: Ramona Bhatia, Chad Achenbach, Rick Kittles, Adam Murphy. Presentation and treatment of prostate cancer in HIV-infected men: Do racial disparities exist. [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 171. doi:10.1158/1538-7445.AM2013-171

Background and Objective: Black men develop and die from prostate cancer (PCa) more than any other racial group. According to recent United States (US) statistics, PCa incidence and mortality rates in Black men are 1.6 and 2.4 times that of their White (WH) counterparts, respectively. Various biologic, behavioral, environmental, demographic, and social-contextual factors have been shown to be components of the persisting disparities in outcomes. However, it is not clear how aspects of body composition, particularly adiposity, contribute to racial and ethnic disparities in PCa occurrence and course. Current reviews on the adiposity relationship have tended not to adequately address this. Therefore, we conducted a systematic review of the literature examining the role of adiposity in racial disparities in prostate cancer. Methods: The US National Library of Medicine National Institutes of Health PubMed database was searched for English articles published through October 1, 2011. Criteria for selection were: 1) an adiposity-related factor (BMI, WHR etc.) was an exposure of interest and related to a PCa outcome (diagnosis, progression, prostate cancer-specific mortality); 2) focused on racial disparities in an adiposity association with PCa; 3) the participant sample included men of predominant African Ancestry [AA] (e.g. Black, African American, Ghanaian etc.); 4) and race-stratified, particularly AA specific, effect estimates for PCa occurrence, mortality, or progression were reported. Adjustment for race in a multivariate model alone was not sufficient for inclusion in the review analysis. No reviews, editorials, or comments were included in the review, although they were cited for background content. Results: Many of the available reviews on adiposity and PCa racial disparities focused on disparities in screening, rather than incidence, progression, or mortality. The articles which did address occurrence and outcomes often did not present race-specific effect estimates and simply adjusted for race in multivariate models. The available evidence suggests a unique role of adiposity-related factors (i.e. body size, body fat distribution, and fatty acid intake,) in the risk of PCa occurrence, progression, differences in treatment efficacy, and PCa-specific death. Lack of studies including sufficiently large numbers of AA prohibited reporting of race-specific estimates in many studies, especially in studies involving molecular biology and genetics. Conclusions: Incidence, morbidity, and mortality are highest in Black men. Clarifying the role of adiposity in PCa disparities is of great importance. Further clinical research illuminating adiposity related targets for intervention and mechanisms is crucial in this highly affected group. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 3598. doi:1538-7445.AM2012-3598

Background: Cancer incidence and mortality rate is disproportionate among the racial/ethnic groups in the U.S. and higher in African Americans (AAs) due to a combination of genes and environmental factors. The difference in serum vitamin D3, 25(OH)D, concentration among racial groups is suspected to be one of the sources of cancer health disparities. Vitamin D has protective effects against several types of cancer, and vitamin D deficiency is more common among AAs than the European Americans (EAs). Genome-Wide Association Studies (GWAS) among EAs found vitamin D pathway gene (VDPG) variants associated with serum 25(OH)D level, but association between VDPG variants and serum 25(OH)D level has not examined in AAs. Here, we tested if thirty-nine VDPG variants are associated with serum 25(OH)D concentration. Samples and Methods: Nineteen variants in GC, VDR, CYP3A4, CYP2R1, and CYP24A1 were genotyped in a total of 462 AAs from Washington, D.C. and Chicago area. Twenty GWAS identified VDPG variants were genotyped in a subset of subjects (n=332). West Africa Ancestry (WAA) was estimated using STRUCTRE from 105 ancestry informative markers typed. Then, we tested for association adjusting for WAA, age, and skin color. Results: Eight GWAS identified SNPs (five in GC, one in CYP2R1, and two in DHCR7/NADSYN1) were associated with serum 25(OH)D levels and/or vitamin D deficiency. Among darker-skinned AAs, the VDR SNP rs11568820 (Cdx2), was significantly associated (P Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 4481. doi:1538-7445.AM2012-4481

Background: Black men develop and die from prostate cancer (PCa) more than any other racial group. According to recent United States (US) statistics, PCa incidence and mortality rates in Black men are 1.6 and 2.4 times that of their White (WH) counterparts, respectively. Various biologic, behavioral, environmental, demographic, and social-contextual factors have been shown to be components of the persisting disparities in outcomes. However, it is not clear how aspects of body composition, particularly adiposity, contribute to racial and ethnic disparities in PCa occurrence and course. Current reviews on the adiposity relationship have tended not to adequately address this. Therefore, we conducted a systematic review of the literature examining the role of adiposity in racial disparities in prostate cancer. Methods: The US National Library of Medicine National Institutes of Health PubMed database was searched for English articles published through October 1, 2011. Criteria for selection were: 1) an adiposity-related factor (BMI, WHR etc.) was an exposure of interest and related to a PCa outcome (diagnosis, progression, prostate cancer-specific mortality); 2) focused on racial disparities in an adiposity association with PCa; 3) the participant sample included men of predominant African Ancestry [AA] (e.g. Black, African American, Ghanaian etc.); 4) and race-stratified, particularly AA specific, effect estimates for PCa occurrence, mortality, or progression were reported. Adjustment for race in a multivariate model alone was not sufficient for inclusion in the review analysis. No reviews, editorials, or comments were included in the review, although they were cited for background content. Results: Many of the available reviews on adiposity and PCa racial disparities focused on disparities in screening, rather than incidence, progression, or mortality. The articles which did address occurrence and outcomes often did not present race-specific effect estimates and simply adjusted for race in multivariate models. The available evidence suggests a unique role of adiposity-related factors (i.e. body size, body fat distribution, and fatty acid intake,) in the risk of PCa occurrence, progression, differences in treatment efficacy, and PCa-specific death. Lack of studies including sufficiently large numbers of AA prohibited reporting of race-specific estimates in many studies, especially in studies involving molecular biology and genetics. Conclusions: Incidence, morbidity, and mortality are highest in Black men. Clarifying the role of adiposity in PCa disparities is of great importance. Further clinical research illuminating adiposity related targets for intervention and mechanisms is crucial in this highly affected group. Citation Format: Iman K. Martin, Leslie T. Stayner, Jocelyn P. Wilder, Abeer M. Mahmoud, Adam B. Murphy, Vincent L. Freeman. The role of adiposity in racial and ethnic disparities in prostate cancer occurrence and progression: A systematic literature review [abstract]. In: Proceedings of the AACR Special Conference on Advances in Prostate Cancer Research; 2012 Feb 6-9; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2012;72(4 Suppl):Abstract nr C59.

Adult height is a classic polygenic trait of high heritability (h 2 ∼0.8). More than 180 single nucleotide polymorphisms (SNPs), identified mostly in populations of European descent, are associated with height. These variants convey modest effects and explain ∼10% of the variance in height. Discovery efforts in other populations, while limited, have revealed loci for height not previously implicated in individuals of European ancestry. Here, we performed a meta-analysis of genome-wide association (GWA) results for adult height in 20,427 individuals of African ancestry with replication in up to 16,436 African Americans. We found two novel height loci (Xp22-rs12393627, P = 3.4×10−12 and 2p14-rs4315565, P = 1.2×10−8). As a group, height associations discovered in European-ancestry samples replicate in individuals of African ancestry (P = 1.7×10−4 for overall replication). Fine-mapping of the European height loci in African-ancestry individuals showed an enrichment of SNPs that are associated with expression of nearby genes when compared to the index European height SNPs (P, Author Summary Adult height is an ideal phenotype to improve our understanding of the genetic architecture of complex diseases and traits: it is easily measured and usually available in large cohorts, relatively stable, and mostly influenced by genetics (narrow-sense heritability of height h 2∼0.8). Genome-wide association (GWA) studies in individuals of European ancestry have identified >180 single nucleotide polymorphisms (SNPs) associated with height. In the current study, we continued to use height as a model polygenic trait and explored the genetic influence in populations of African ancestry through a meta-analysis of GWA height results from 20,809 individuals of African descent. We identified two novel height loci not previously found in Europeans. We also replicated the European height signals, suggesting that many of the genetic variants that are associated with height are shared between individuals of European and African descent. Finally, in fine-mapping the European height loci in African-ancestry individuals, we found SNPs more likely to be associated with the expression of nearby genes than the SNPs originally found in Europeans. Thus, our results support the utility of performing genetic studies in non-European populations to gain insights into complex human diseases and traits.

Background: Prostate cancer (Pca) is the most common type of cancer among men in the United States, and its disproportionate incidence and mortality rates among ethnic groups are likely due to a combination of genes and environmental factors. While genome-wide association studies (GWASs) of European descents have identified candidate loci associated with Pca risk, including rs4072111 located in IL-16, the replication studies in African Americans (AAs) have been inconsistent, and GWASs have not yet produced many findings to resolve Pca health disparities. IL-16 is over-expressed in tumor cells possibly mediating expression of other cytokines that promote tumor growth. Here we explore SNP variation in IL-16 in AAs and test for association with Pca in AAs. Method: Two hundred and seventy-seven (277) tagging SNPs spanning IL-16 (79.20Mb to 79.45Mb on chromosome 15) were genotyped in 496 AA Pca cases and 501 controls from Washington, DC. In order to replicate our findings, 11 of the SNPs were also typed in additional 400 AA Pca cases and controls from Chicago, IL. One hundred (100) unlinked ancestry informative markers were also typed for each sample. West African genetic ancestry estimates were obtained using STRUCTURE. We tested for allelic association and calculated odds ratios using logistic regression, adjusting for West African ancestry and age. Empiric p-values were obtained by adaptive permutation. Results: Our first stage analyses revealed that a cluster of 20 IL-16 SNPs were significantly associated with Pca risk. The strongest association was found at rs7175701 (P=1.2 × 10−8), which lies within intron 26 of IL-16. In the replication population, two SNPs, slightly linked to rs7175701, but within the 3′UTR region were also strongly associated with Pca risk (P Our study provides evidence that IL-16 polymorphisms likely play a role to Pca susceptibility in AAs. Many of the significantly associated SNPs are linked to rs11325 which is a candidate SNP for a miRNA target region in IL-16. Although the exact mechanism is unclear, additional functional studies are warranted. Impact: Our findings are significant given that there has been limited focus on the role of IL-16 genetic polymorphisms on Pca risk in AAs. Understanding the role of cytokines such as IL-16 in tumor growth in diverse populations is important, and could likely lead to the development of useful biomarkers for cancer screening and/or potential therapeutics. Citation Information: Cancer Epidemiol Biomarkers Prev 2011;20(10 Suppl):A67.

Introduction: Elevated serum total testosterone (TT) levels have been associated with increased prostate cancer incidence and mortality faced by African American (AA) men. Testosterone deficiency (TD) is linked to several health outcomes including increased cancer and all-cause mortality. Several studies have examined the relationships between TT levels and biochemical and environmental factors, but few have examined these correlates in AA men. This study evaluated TT levels, TD and their correlates in AA men. Methods: Blood samples were collected from 191 controls recruited from 2000–2003 from the Urology clinic at the Howard University Hospital, along with demographic data, reported alcohol use, and BMI. Measurements of testosterone (total and free), prostate specific antigen (PSA), triglycerides (TG), total cholesterol, HDL, VLDL, LDL, IGF1 and IGFBP3 levels were obtained from the blood. Percentage west African genetic ancestry was determined using a panel of 100 ancestry informative markers. Results: On linear regression, age, HDL, LDL and IGFBP3 levels were associated with TT levels (p< 0.05). However, TT levels were not associated with degree of West African ancestry (p = 0.52). Using multivariate analysis, TD deficiency (TT < 300 ng/dL) was positively associated with TG levels (p < 0.05), alcohol use and elevated BMI (p = 0.018 for both). The highest quartile BMI (BMI > 31) was at 2.48 times higher risk for TD than the lowest quartile (< 25). The correlates of TT levels and risk factors for TD in AA men are similar to the established risk factors in European American men. Citation Information: Cancer Epidemiol Biomarkers Prev 2011;20(10 Suppl):A93.

GWAS of prostate cancer have been remarkably successful in revealing common genetic variants and novel biological pathways that are linked with its etiology. A more complete understanding of inherited susceptibility to prostate cancer in the general population will come from continuing such discovery efforts and from testing known risk alleles in diverse racial and ethnic groups. In this large study of prostate cancer in African American men (3,425 prostate cancer cases and 3,290 controls), we tested 49 risk variants located in 28 genomic regions identified through GWAS in men of European and Asian descent, and we replicated associations (at p≤0.05) with roughly half of these markers. Through fine-mapping, we identified nearby markers in many regions that better define associations in African Americans. At 8q24, we found 9 variants (p≤6×10−4) that best capture risk of prostate cancer in African Americans, many of which are more common in men of African than European descent. The markers found to be associated with risk at each locus improved risk modeling in African Americans (per allele OR = 1.17) over the alleles reported in the original GWAS (OR = 1.08). In summary, in this detailed analysis of the prostate cancer risk loci reported from GWAS, we have validated and improved upon markers of risk in some regions that better define the association with prostate cancer in African Americans. Our findings with variants at 8q24 also reinforce the importance of this region as a major risk locus for prostate cancer in men of African ancestry., Author Summary Prostate cancer is one of the most common cancers in men and is especially frequent in men of African origin, as incidence rates in African Americans in the United States are >1.5–fold greater than rates in European Americans. In order to gain a more complete understanding of the genetic basis of inherited susceptibility to prostate cancer in men of African origin, we examined the associations at risk loci identified in men of European and Asian descent in a large African American sample of 3,425 cases of prostate cancer and 3,290 male controls. In testing 49 known risk variants, we were able to demonstrate that at least half of these variants also contribute to risk in African American men. We were able to find additional risk variants in many of the previously reported regions that better captured the pattern of risk in African American men. In addition, we verified and improved upon the evidence we previously reported that there are multiple risk variants in a region of 8q24 that are important in men of African origin.

Background African Americans have disproportionately higher burden of prostate cancer compared to European Americans. However, the cause of prostate cancer disparities is still unclear. Several roles have been proposed for calcium and vitamin D in prostate cancer pathogenesis and progression, but epidemiologic studies have been conducted mainly in European descent populations. Here we investigated the association of calcium and vitamin D intake with prostate cancer in multiethnic samples. Methods A total of 1,657 prostate cancer patients who underwent screening and healthy controls (888 African Americans, 620 European Americans, 111 Hispanic Americans, and 38 others) from Chicago, IL and Washington, D.C. were included in this study. Calcium and vitamin D intake were evaluated using food frequency questionnaire. We performed unconditional logistic regression analyses adjusting for relevant variables. Results In the pooled data set, high calcium intake was significantly associated with higher odds for aggressive prostate cancer (ORQuartile 1 vs. Quartile 4 = 1.98, 95% C.I.: 1.01–3.91), while high vitamin D intake was associated with lower odds of aggressive prostate cancer (ORQuartile 1 vs. Quartile 4 = 0.38, 95% C.I.: 0.18–0.79). In African Americans, the association between high calcium intake and aggressive prostate cancer was statistically significant (ORQuartile 1 vs. Quartile 4 = 4.28, 95% C.I.: 1.70–10.80). We also observed a strong inverse association between total vitamin D intake and prostate cancer in African Americans (ORQuartile 1 vs. Quartile 4 = 0.06, 95% C.I.: 0.02–0.54). In European Americas, we did not observe any significant associations between either calcium or vitamin D intake and prostate cancer. In analyses stratifying participants based on Body Mass Index (BMI), we observed a strong positive association between calcium and aggressive prostate cancer and a strong inverse association between vitamin D intake and aggressive prostate cancer among men with low BMI (