Performance of prostate cancer recurrence nomograms by obesity status: a retrospective analysis of a radical prostatectomy cohort.

BACKGROUND: Obesity has been associated with aggressive prostate cancer and poor outcomes. It is important to understand how prognostic tools for that guide prostate cancer treatment may be impacted by obesity. The goal of this study was to evaluate the predicting abilities of two prostate cancer (PCa) nomograms by obesity status. METHODS: We examined 1576 radical prostatectomy patients categorized into standard body mass index (BMI) groups. Patients were categorized into low, medium, and high risk groups for the Kattan and CaPSURE/CPDR scores, which are based on PSA value, Gleason score, tumor stage, and other patient data. Time to PCa recurrence was modeled as a function of obesity, risk group, and interactions. RESULTS: As expected for the Kattan score, estimated hazard ratios (95% CI) indicated higher risk of recurrence for medium (HR = 2.99, 95% CI = 2.29, 3.88) and high (HR = 8.84, 95% CI = 5.91, 13.2) risk groups compared to low risk group. The associations were not statistically different across BMI groups. Results were consistent for the CaPSURE/CPDR score. However, the difference in risk of recurrence in the high risk versus low risk groups was larger for normal weight patients than the same estimate in the obese patients. CONCLUSIONS: We observed no statistically significant difference in the association between PCa recurrence and prediction scores across BMI groups. However, our study indicates that there may be a stronger association between high risk status and PCa recurrence among normal weight patients compared to obese patients. This suggests that high risk status based on PCa nomogram scores may be most predictive among normal weight patients. Additional research in this area is needed.

Telomere Length and Neighborhood Circumstances: Evaluating Biological Response to Unfavorable Exposures.

Background: Multilevel frameworks suggest neighborhood circumstances influence biology; however, this relationship is not well studied. Telomere length (TL) shortening has been associated with individual-level and neighborhood-level exposures and disease and may provide insights into underlying biologic mechanisms linking neighborhood with biology. To support neighborhood-biology investigations, we sought to determine the independent effect of neighborhood exposures on TL using standard multilevel linear regression models and quantile regression, a nonlinear, social science method applicable for testing the biologic hypothesis that extremes of the TL distribution are related to poor outcomes.Methods: In a multicenter, cross-sectional study, blood TL was measured in 1,488 individuals from 127 census tracts in three U.S. regions using terminal restriction fragment assays. Multilevel linear and quantile regression models were adjusted for individual-level race, education, perceived stress, and depression. Neighborhood exposures included population density, urban/residential crowding, residential stability/mobility, and socioeconomic status.Results: TL was not associated with any neighborhood variable using linear models, but quantile regression revealed inverse associations between population density and urban crowding at the lower tails of the TL distribution [5th (population density P = 0.03; urban crowding P = 0.002), 50th (both P < 0.001), 75th percentiles (both P < 0.001)]. TL was related to residential stability at the upper tail (95th percentile P = 0.006).Conclusions: Findings support the use of nonlinear statistical methods in TL research and suggest that neighborhood exposures can result in biological effects.Impact: TL may serve as an underlying example of a biologic mechanism that can link neighborhood with biology, thus supporting multilevel investigations in future studies. Cancer Epidemiol Biomarkers Prev; 26(4); 553-60. ©2017 AACRSee all the articles in this CEBP Focus section, "Geospatial Approaches to Cancer Control and Population Sciences."

The impact of body mass index on treatment outcomes for patients with low-intermediate risk prostate cancer.

BACKGROUND: Little is known about the relationship between preoperative body mass index and need for adjuvant radiation therapy (RT) following radical prostatectomy. The goal of this study was to evaluate the utility of body mass index in predicting adverse clinical outcomes which require adjuvant RT among men with organ-confined prostate cancer (PCa). METHODS: We used a prospective cohort of 1,170 low-intermediate PCa risk men who underwent radical prostatectomy and evaluated the effect of body mass index on adverse pathologic features and freedom from biochemical failure (FFbF). Clinical and pathologic variables were compared across the body mass index groups using an analysis of variance model for continuous variables or χ(2) for categorical variables. Factors related to adverse pathologic features were examined using logistic regression models. Time to biochemical recurrence was compared across the groups using a log-rank survivorship analysis. Multivariable analysis predicting biochemical recurrence was conducted with a Cox proportional hazards model. RESULTS: Patients with elevated body mass index (defined as body mass index ≥25 kg/m(2)) had greater extraprostatic extension (p = 0.004), and positive surgical margins (p = 0.01). Elevated body mass index did not correlate with preoperative risk groupings (p = 0.94). However, when compared with non-obese patients (body mass index <30 kg/m(2)), obese patients (body mass index ≥30 kg/m(2)) were much more likely to have higher rate of adverse pathologic features (p = 0.006). In patients with low- and intermediate- risk disease, obesity was strongly associated with rate of pathologic upgrading of tumors (p = 0.01 and p = 0.02), respectively. After controlling for known preoperative risk factors, body mass index was independently associated with ≥2 adverse pathologic features (p = 0.002), an indicator for adjuvant RT as well as FFbF (p = 0.001). CONCLUSIONS: Body mass index of ≥30 kg/m(2) is independently associated with adverse pathologic features, which is an indicator for additional RT, particularly in patients with low-intermediate risk disease. Future studies may determine if this select group of patients may be best treated with definitive RT to reduce toxicity from additional RT following radical prostatectomy. We propose including body mass index in clinical decision-making for appropriate treatment recommendation for patients with low-intermediate risk PCa.

Race, Ethnicity, Psychosocial Factors, and Telomere Length in a Multicenter Setting.

BACKGROUND: Leukocyte telomere length(LTL) has been associated with age, self-reported race/ethnicity, gender, education, and psychosocial factors, including perceived stress, and depression. However, inconsistencies in associations of LTL with disease and other phenotypes exist across studies. Population characteristics, including race/ethnicity, laboratory methods, and statistical approaches in LTL have not been comprehensively studied and could explain inconsistent LTL associations. METHODS: LTL was measured using Southern Blot in 1510 participants from a multi-ethnic, multi-center study combining data from 3 centers with different population characteristics and laboratory processing methods. Main associations between LTL and psychosocial factors and LTL and race/ethnicity were evaluated and then compared across generalized estimating equations(GEE) and linear regression models. Statistical models were adjusted for factors typically associated with LTL(age, gender, cancer status) and also accounted for factors related to center differences, including laboratory methods(i.e., DNA extraction). Associations between LTL and psychosocial factors were also evaluated within race/ethnicity subgroups (Non-hispanic Whites, African Americans, and Hispanics). RESULTS: Beyond adjustment for age, gender, and cancer status, additional adjustments for DNA extraction and clustering by center were needed given their effects on LTL measurements. In adjusted GEE models, longer LTL was associated with African American race (Beta(ß)(standard error(SE)) = 0.09(0.04), p-value = 0.04) and Hispanic ethnicity (ß(SE) = 0.06(0.01), p-value = 0.02) compared to Non-Hispanic Whites. Longer LTL was also associated with less than a high school education compared to having greater than a high school education (ß(SE) = 0.06(0.02), p-value = 0.04). LTL was inversely related to perceived stress (ß(SE) = -0.02(0.003), p<0.001). In subgroup analyses, there was a negative association with LTL in African Americans with a high school education versus those with greater than a high school education(ß(SE) = -0.11(0.03), p-value<0.001). CONCLUSIONS: Laboratory methods and population characteristics that differ by center can influence telomere length associations in multicenter settings, but these effects could be addressed through statistical adjustments. Proper evaluation of potential sources of bias can allow for combined multicenter analyses and may resolve some inconsistencies in reporting of LTL associations. Further, biologic effects on LTL may differ under certain psychosocial and racial/ethnic circumstances and could impact future health disparity studies.

Individual- and neighborhood-level education influences the effect of obesity on prostate cancer treatment failure after prostatectomy.

PURPOSE: The relationship between obesity and prostate cancer (CaP) treatment failure is complex and may vary by patient- and neighborhood-level educational attainment. We evaluated whether patient- and neighborhood-level education is associated with the effect of obesity on biochemical recurrence. METHODS: Seven hundred and forty-six CaP cases were classified into four groups: Concordant Low-Low: less educated cases (<4 years college) living in a less educated neighborhood (below-median proportion of college-educated residents; n = 164); Concordant High-High: highly educated cases (≥ 4 years college) living in a highly educated neighborhood (above-median proportion of college-educated residents; n = 326); Discordant Low-High: less educated cases living in a highly educated neighborhood (n = 69); and Discordant High-Low: highly educated cases living in a less educated neighborhood (n = 187). Cox regression models were used to examine associations between obesity and biochemical (PSA) failure after prostatectomy stratified by the concordant/discordant groups. RESULTS: The association of obesity with biochemical failure varied significantly by educational concordance/discordance (p = 0.007). Obesity was associated with risk of biochemical failure for less educated cases residing in less educated neighborhoods (HR 3.72, 95% CI 1.30-10.65). The relationship was not significant for other concordant/discordant groups. CONCLUSIONS: Obesity effects on CaP outcomes vary by multilevel educational discordance/concordance. Strategies to decrease prostate cancer risk of progression may focus on reduction in obesity, particularly for less educated cases residing in less educated neighborhoods.

African American men with low-grade prostate cancer have increased disease recurrence after prostatectomy compared with Caucasian men.

PURPOSE: To explore whether disparities in outcomes exist between African American (AA) and Caucasian (CS) men with low-grade prostate cancer and similar cancer of the prostate risk assessment-postsurgery (CAPRA-S) features following prostatectomy (RP). METHODS: The overall cohort consisted of 1,265 men (234 AA and 1,031 CS) who met the National comprehensive cancer network criteria for low- to intermediate-risk prostate cancer and underwent RP between 1990 and 2012. We first evaluated whether clinical factors were associated with adverse pathologic outcomes and freedom from biochemical failure (FFbF) using the entire cohort. Next, we studied a subset of 705 men (112 AA and 593 CS) who had pathologic Gleason score≤6 (low-grade disease). Using this cohort, we determined whether race affected FFbF in men with RP-proven low-grade disease and similar CAPRA-S scores. RESULTS: With a median follow-up time of 27 months, the overall 7-year FFbF rate was 86% vs. 79% in CS and AA men, respectively (P = 0.035). There was no significant difference in one or more adverse pathologic features between CS vs. AA men (27% vs. 31%; P = 0.35) or CAPRA-S score (P = 0.28). In the subset analysis of patients with low-grade disease, AA race was associated with worse FFbF outcomes (P = 0.002). Furthermore, AA race was a significant predictor of FFbF in men with low-grade disease (hazard ratio = 2.01, 95% CI: 1.08-3.72; P = 0.029). CONCLUSIONS: AA race is a predictor of worse FFbF outcomes in men with low-grade disease after RP. These results suggest that a subset of AA men with low-grade disease may benefit from more aggressive treatment.

Supervised multi-view canonical correlation analysis (sMVCCA): integrating histologic and proteomic features for predicting recurrent prostate cancer.

In this work, we present a new methodology to facilitate prediction of recurrent prostate cancer (CaP) following radical prostatectomy (RP) via the integration of quantitative image features and protein expression in the excised prostate. Creating a fused predictor from high-dimensional data streams is challenging because the classifier must 1) account for the "curse of dimensionality" problem, which hinders classifier performance when the number of features exceeds the number of patient studies and 2) balance potential mismatches in the number of features across different channels to avoid classifier bias towards channels with more features. Our new data integration methodology, supervised Multi-view Canonical Correlation Analysis (sMVCCA), aims to integrate infinite views of highdimensional data to provide more amenable data representations for disease classification. Additionally, we demonstrate sMVCCA using Spearman's rank correlation which, unlike Pearson's correlation, can account for nonlinear correlations and outliers. Forty CaP patients with pathological Gleason scores 6-8 were considered for this study. 21 of these men revealed biochemical recurrence (BCR) following RP, while 19 did not. For each patient, 189 quantitative histomorphometric attributes and 650 protein expression levels were extracted from the primary tumor nodule. The fused histomorphometric/proteomic representation via sMVCCA combined with a random forest classifier predicted BCR with a mean AUC of 0.74 and a maximum AUC of 0.9286. We found sMVCCA to perform statistically significantly (p < 0.05) better than comparative state-of-the-art data fusion strategies for predicting BCR. Furthermore, Kaplan-Meier analysis demonstrated improved BCR-free survival prediction for the sMVCCA-fused classifier as compared to histology or proteomic features alone.

African-american race is a predictor of seminal vesicle invasion after radical prostatectomy.

INTRODUCTION: The purpose of the study was to determine whether racial differences exist in the pattern of local disease progression among men treated with radical prostatectomy (RP) for localized prostate cancer (PCa), which is currently unknown. In this study we evaluated the pattern of adverse pathologic features in an identical cohort of African-American (AA) and Caucasian (CS) men with PCa. PATIENTS AND METHODS: The overall cohort consisted of 1104 men (224 AA, and 880 CS) who underwent RP between 1990 and 2012. We compared preoperative factors and pathologic outcomes after RP across race groups. Multivariate analysis was used to identify factors predictive of adverse pathologic outcomes. The effect of race on adverse pathologic outcomes and biochemical control rate (BCR) was evaluated using multivariate regression model and Kaplan-Meier analysis. RESULTS: The 10-year BCR was 59% versus 82% in AA and CS men, respectively (P = .003). There was no significant difference in extraprostatic spread (P = .14), positive surgical margin (P = .81), lymph node involvement (P = .71), or adverse pathologic features (P = .16) across race groups. However, among patients with ≥ 1 adverse pathologic features, AA men had higher rate of seminal vesicle invasion (SVI) compared with CS men (51% vs. 30%; P = .01). After adjusting for known predictors of adverse pathologic features AA race remained a predictor of SVI. CONCLUSION: AA men have an increased risk of SVI after RP, particularly among men with Gleason ≤ 6 disease. This might represent racial differences in the biology of PCa disease progression, which contribute to poorer outcomes in AA men.

Co-occurring gland angularity in localized subgraphs: predicting biochemical recurrence in intermediate-risk prostate cancer patients.

Quantitative histomorphometry (QH) refers to the application of advanced computational image analysis to reproducibly describe disease appearance on digitized histopathology images. QH thus could serve as an important complementary tool for pathologists in interrogating and interpreting cancer morphology and malignancy. In the US, annually, over 60,000 prostate cancer patients undergo radical prostatectomy treatment. Around 10,000 of these men experience biochemical recurrence within 5 years of surgery, a marker for local or distant disease recurrence. The ability to predict the risk of biochemical recurrence soon after surgery could allow for adjuvant therapies to be prescribed as necessary to improve long term treatment outcomes. The underlying hypothesis with our approach, co-occurring gland angularity (CGA), is that in benign or less aggressive prostate cancer, gland orientations within local neighborhoods are similar to each other but are more chaotically arranged in aggressive disease. By modeling the extent of the disorder, we can differentiate surgically removed prostate tissue sections from (a) benign and malignant regions and (b) more and less aggressive prostate cancer. For a cohort of 40 intermediate-risk (mostly Gleason sum 7) surgically cured prostate cancer patients where half suffered biochemical recurrence, the CGA features were able to predict biochemical recurrence with 73% accuracy. Additionally, for 80 regions of interest chosen from the 40 studies, corresponding to both normal and cancerous cases, the CGA features yielded a 99% accuracy. CGAs were shown to be statistically signicantly ([Formula: see text]) better at predicting BCR compared to state-of-the-art QH methods and postoperative prostate cancer nomograms.

Gender- and ethnic-specific associations with obesity: individual and neighborhood-level factors.

OBJECTIVES: Gender- and ethnicity-specific groups face different risks for obesity, but little is understood about the factors that predict group-specific risks. We evaluated individual and neighborhood factors in relation to obesity. DESIGN: Cross-sectional surveys of adults (ages 18-100 years) from southeastern Pennsylvania were analyzed. Individual- and neighborhood-level factors were included in fully-adjusted regression models to estimate relationships with obesity for specific gender-ethnic groups. The study included 679 Asian women, 655 Asian men, 4190 African-American women, 1568 African-American men, 1248 Hispanic women, 586 Hispanic men, 11791 European American women, and 6547 European American men. RESULTS: There were significant differences in the predictors of obesity by gender-ethnic groups. Obesity was differentially associated with age (p < 0.001, positively associated with middle age in African-American men and in all women except Asian; positively associated with older age in European American women but inversely in African-American men and European American men), employment (p < 0.01, positively associated in African-American men and European American men) and poverty (p < 0.001, positively associated in Asian men, African-American women, and European American women). Reporting good/excellent health was differentially associated with less obesity (p < 0.01, no association for African-American men and Asians). Interestingly, neighborhood-level effects, however, did not differ significantly by gender-ethnic group. Inverse neighborhood effects on obesity prevalence were observed in most groups for higher neighborhood education and family income. Direct associations with obesity were observed for neighborhood poverty and neighborhood smoking. CONCLUSIONS: We observed that individual- and neighborhood-level variables are associated with obesity. Several individual-level effects differ by gender-ethnic group.

Relationship of early-onset baldness to prostate cancer in African-American men.

BACKGROUND: Early-onset baldness has been linked to prostate cancer; however, little is known about this relationship in African-Americans who are at elevated prostate cancer risk. METHODS: We recruited 219 African-American controls and 318 African-American prostate cancer cases. We determined age-stratified associations of baldness with prostate cancer occurrence and severity defined by high stage (T3/T4) or high grade (Gleason 7+.) Associations of androgen metabolism genotypes (CYP3A4, CYP3A5, CYP3A43, AR-CAG, SRD5A2 A49T, and SRD5A2 V89L), family history, alcohol intake, and smoking were examined by baldness status and age group by using multivariable logistic regression models. RESULTS: Baldness was associated with odds of prostate cancer [OR = 1.69; 95% confidence interval (CI), 1.05-2.74]. Frontal baldness was associated with high-stage (OR = 2.61; 95% CI, 1.10-6.18) and high-grade (OR = 2.20; 95% CI, 1.05-4.61) tumors. For men diagnosed less than the age of 60 years, frontal baldness was associated with high stage (OR = 6.51; 95% CI, 2.11-20.06) and high grade (OR = 4.23; 95% CI, 1.47-12.14). We also observed a suggestion of an interaction among smoking, median age, and any baldness (P = 0.02). CONCLUSIONS: We observed significant associations between early-onset baldness and prostate cancer in African-American men. Interactions with age and smoking were suggested in these associations. Studies are needed to investigate the mechanisms influencing the relationship between baldness and prostate cancer in African-American men. IMPACT: African-American men present with unique risk factors including baldness patterns that may contribute to prostate cancer disparities.

What stresses men? Predictors of perceived stress in a population-based multi-ethnic cross sectional cohort.

BACKGROUND: Perceived stress (PS) is a risk factor for a variety of diseases. However, relatively little is known about age- or ethnicity-specific differences in the effect of potential predictors of PS in men. METHODS: We used a population-based survey of 6,773 White, 1,681 Black, and 617 Hispanic men in Southeastern Pennsylvania to evaluate the relationship of self-reported PS and financial security, health status, social factors, and health behaviors. Interactions across levels of age and ethnicity were tested using logistic regression models adjusted for overall health status, education, and household poverty. RESULTS: High PS decreased significantly with age (p < 0.0001) and varied by ethnicity (p = 0.0001). Exposure to health-related and economic factors were more consistently associated with elevated PS in all ethnicities and ages, while social factors and health behaviors were less strongly or not at all associated with PS in most groups. Significant differences in the relationship of high PS by age and ethnicity were observed among men who are medically uninsured (p = 0.0002), reported missing a meal due to cost (p < 0.0001), or had spent a night in the hospital (p = 0.020). In contrast, not filling a prescription due to cost and diagnosed with a mental health condition were associated with high PS but did not differ by age and ethnicity subgroup. CONCLUSIONS: These data suggest that some, but not all, factors associated with high PS differ by age and/or ethnicity. Research, clinical, or public health initiatives that involve social stressors should consider differences by age and ethnicity.

Androgen Metabolism Gene Polymorphisms, Associations with Prostate Cancer Risk and Pathological Characteristics: A Comparative Analysis between South African and Senegalese Men.

Prostate cancer is the most common cancer in men in developed countries and the leading cause of mortality in males in less developed countries. African ethnicity is one of the major risk factors for developing prostate cancer. Pathways involved in androgen metabolism have been implicated in the etiology of the disease. Analyses of clinical data and CYP3A4, CYP3A5, and SRD5A2 genotypes were performed in South African White (120 cases; 134 controls), Mixed Ancestry (207 cases; 167 controls), and Black (25 cases; 20 controls) men, as well as in Senegalese men (86 cases; 300 controls). Senegalese men were diagnosed earlier with prostate cancer and had higher median PSA levels compared to South African men. Metastasis occurred more frequently in Senegalese men. Gene polymorphism frequencies differed significantly between South African and Senegalese men. The CYP3A4 rs2740574 polymorphism was associated with prostate cancer risk and tumor aggressiveness in South African men, after correction for population stratification, and the SRD5A2 rs523349 CG genotype was inversely associated with high-stage disease in Senegalese men. These data suggest that variants previously associated with prostate cancer in other populations may also affect prostate cancer risk in African men.

Relationship of obesity, androgen receptor genotypes and biochemical failure after radical prostatectomy.

BACKGROUND: Obesity and androgen metabolism have been implicated in the progression of prostate cancer. Obesity has been associated with increased risk for advanced disease and biochemical failure after treatment. This association may be the result of changes in androgen metabolism that occur with obesity and are mediated by the androgen receptor (AR). METHODS: To evaluate the effects of obesity and AR polymorphisms on biochemical failure, we conducted a study of 536 Caucasian prostate cancer cases. We determined the relationship between time to biochemical failure and obesity stratified by short and long AR-CAG and AR-GGN repeat sequence. The AR repeat groups were dichotomized at the median number of repeats for each polymorphism. RESULTS: An association was found for obesity in the short CAG group (HR = 3.45, 95% CI = 1.00-11.96). Among obese patients diagnosed with localized disease (T1/T2), the risk of biochemical failure was significantly higher (HR = 7.05, 95% CI = 1.55-32.06). No difference was observed for high stage (T3/T4) obese patients. Additionally, no differences in biochemical failure were observed in obese and non-obese men grouped by number of AR-GGN repeats. CONCLUSIONS: Obesity is significantly associated with increased risk of biochemical failure in men with the high-risk short CAG sequence on the AR gene. This effect is not observed in men with long CAG repeats. Therefore, it appears that the relationship between biochemical failure and obesity may be modified by the AR-CAG repeat pattern. The short AR-CAG genotype may be more responsive to an altered hormonal milieu created by obesity.

Validation of genome-wide prostate cancer associations in men of African descent.

BACKGROUND: Genome-wide association studies (GWAS) have identified numerous prostate cancer susceptibility alleles, but these loci have been identified primarily in men of European descent. There is limited information about the role of these loci in men of African descent. METHODS: We identified 7,788 prostate cancer cases and controls with genotype data for 47 GWAS-identified loci. RESULTS: We identified significant associations for SNP rs10486567 at JAZF1, rs10993994 at MSMB, rs12418451 and rs7931342 at 11q13, and rs5945572 and rs5945619 at NUDT10/11. These associations were in the same direction and of similar magnitude as those reported in men of European descent. Significance was attained at all reported prostate cancer susceptibility regions at chromosome 8q24, including associations reaching genome-wide significance in region 2. CONCLUSION: We have validated in men of African descent the associations at some, but not all, prostate cancer susceptibility loci originally identified in European descent populations. This may be due to the heterogeneity in genetic etiology or in the pattern of genetic variation across populations. IMPACT: The genetic etiology of prostate cancer in men of African descent differs from that of men of European descent.

Context-dependent effects of genome-wide association study genotypes and macroenvironment on time to biochemical (prostate specific antigen) failure after prostatectomy.

BACKGROUND: Disparities in cancer defined by race, age, or gender are well established. However, demographic metrics are surrogates for the complex contributions of genotypes, exposures, health care, socioeconomic and sociocultural environment, and many other factors. Macroenvironmental factors represent novel surrogates for exposures, lifestyle, and other factors that are difficult to measure but might influence cancer outcomes. METHODS: We applied a "multilevel molecular epidemiology" approach using a prospective cohort of 444 White prostate cancer cases who underwent prostatectomy and were followed until biochemical failure (BF) or censoring without BF. We applied Cox regression models to test for joint effects of 86 genome-wide association study-identified genotypes and macroenvironment contextual effects after geocoding all cases to their residential census tracts. All analyses were adjusted for age at diagnosis and tumor aggressiveness. RESULTS: Residents living in census tracts with a high proportion of older single heads of household, high rates of vacant housing, or high unemployment had shorter time until BF postsurgery after adjustment for patient age and tumor aggressiveness. After correction for multiple testing, genotypes alone did not predict time to BF, but interactions predicting time to BF were observed for MSMB (rs10993994) and percentage of older single heads of households (P = 0.0004), and for HNF1B/TCF2 (rs4430796) and census tract per capita income (P = 0.0002). CONCLUSIONS: The context-specific macroenvironmental effects of genotype might improve the ability to identify groups that might experience poor prostate cancer outcomes. IMPACT: Risk estimation and clinical translation of genotype information might require an understanding of both individual- and macroenvironment-level context.

Dietary intake of Senegalese adults.

The aim of this work is to identify major food sources and dietary constituents of Senegalese adults. We conducted a cross-sectional study, using a single 24-hour dietary recall interview. Foods were classified into food groups based on similarities in nutrient content or use. Food groups included foods consumed individually, or as part of food mixtures such as stews, soups, or sandwiches. Median consumption (amount/day) of each food was determined and examined by relevant subgroups. Participants were 50 healthy Senegalese men, aged 20-62 years recruited at the Hôpital Général de Grand Yoff in Dakar, Senegal and from Sendou village, a rural area outside Dakar. A total of 90 foods and beverages were identified and classified into 11 groups. Sixty-five percent of foods identified could be classified as meats, grains, or fruits/vegetables. Fruits and vegetables comprised 42% (38/90) of all foods; meats 12% (11/90); and grains 11% (10/90). Sauces (6%, 5/90), sweets (4%, 4/90), and desserts (4%, 4/90) were also reported. The most common fruits/vegetables reported were potato, carrot, mango, and lettuce; commonly reported grains were bread and rice; and commonly reported meats were fish, beef, and ox. There were no differences in reported daily intake of each food by age, ethnicity, education, or residence. Most foods reported were traditional to the Senegalese diet, despite the increasing availability of Western foods in Senegal.

Joint effects of inflammation and androgen metabolism on prostate cancer severity.

Multiple pathways of prostate carcinogenesis have been proposed, including those involving androgen metabolism and inflammation. These pathways are not independent, and may act together in prostate cancer etiology: androgens promote both inflammatory processes and serve as mitogens in prostate tumor growth. To explore the possible joint effects of these pathways in prostate cancer severity, we studied 1,090 Caucasian prostate cancer cases to evaluate whether tumor severity is influenced by a history of benign prostatic hyperplasia (BPH) interacting with genotypes involved in inflammation or androgen metabolism including MSR1, RNASEL, AR, CYP3A4, CYP3A43, CYP3A5 and SRD5A2. We observed a statistically significant interaction between a number of genotypes and BPH. After considering the potential for false positive associations, the only remaining significant associations involved CYP3A43 P340A genotypes and history of BPH on both Gleason grade (interaction p-value = 0.026) and tumor stage (interaction p-value = 0.017). These results suggest that androgen metabolism may act in concert with inflammatory phenotypes such as BPH in determining prostate cancer severity.

Genetic susceptibility to prostate cancer in men of African descent: implications for global disparities in incidence and outcomes.

INTRODUCTION: Disparities in prostate cancer incidence and outcomes are a hallmark of the global pattern of prostate cancer, with men of African descent suffering disproportionately from this disease. The causes of these disparities are poorly understood. METHODS: A review of the literature was undertaken to evaluate the role that genetic susceptibility may play in prostate cancer etiology and outcomes, with a particular emphasis on disparities. RESULTS: The genetic contribution to prostate cancer is well established, and a number of candidate prostate cancer genes have been identified. Significant differences in the frequency of risk alleles in these genes have been identified across the major races. These allele frequency differences may in part explain an increased susceptibility to prostate cancer in some populations. In addition, non-genetic factors contribute significantly to prostate cancer disparities, and the cumulative contribution of both genetic and non-genetic factors to poor-prognosis prostate cancer may explain the poorer outcomes experienced by men of African descent. CONCLUSIONS: Prostate cancer disparities are a function of genetic susceptibility as well as environment, behavior, and health care factors acting in the context of this genetic susceptibility. Elimination of global prostate cancer disparities requires a full understanding of the effects of all of these factors on prostate cancer etiology and outcomes.

Association of susceptibility alleles in ELAC2/HPC2, RNASEL/HPC1, and MSR1 with prostate cancer severity in European American and African American men.

Reported associations of ELAC2/HPC2, RNASEL/HPC1, and MSR1 with prostate cancer have been inconsistent and understudied in African Americans. We evaluated the role of 16 sequence variants in these genes with prostate cancer using 888 European American and 131 African American cases, and 473 European American and 163 African American, controls. We observed significant differences in ELAC2, RNASEL, and MSR1 allele frequencies by race. However, we did not observe significant associations between prostate cancer and any variants examined for both races combined. Associations were observed when stratified by race, family history, or disease severity. European American men homozygous for MSR1 IVS7delTTA had an elevated risk for localized stage [odds ratio, (OR), 3.5; 95% confidence interval (95% CI), 1.4-6.9], low-grade (OR, 3.2; 95% CI, 1.4-7.3) disease overall, and with low-grade (OR, 2.9; 95% CI, 1.2-7.2) or late-stage disease (OR, 5.2; 95% CI, 1.1-25.7) in family history-negative African Americans. MSR1 Arg293X was associated with family history-negative high-grade disease (OR, 4.0; 95% CI, 1.1-14.1) in European Americans. RNASEL Arg462Gln was associated with low-grade (OR, 1.5; 95% CI, 1.04-2.2) and early-stage (OR, 1.5; 95% CI, 1.02-2.1) disease in family history-negative European Americans. In family history-positive individuals, Arg462Gln was inversely associated with low-grade (OR, 0.43; 95% CI, 0.21-0.88) and low-stage (OR, 0.46; 95% CI, 0.22-0.95) disease. In African Americans, Arg462Gln was associated with positive family history high-stage disease (OR, 14.8; 95% CI, 1.6-135.7). Meta-analyses revealed significant associations of prostate cancer with MSR1 IVS7delTTA, -14,742 A>G, and Arg293X in European Americans; Asp174Tyr in African Americans; RNASEL Arg462Gln in European American's overall and in family history-negative disease; and Glu265X in family history-positive European Americans. Therefore, MSR1 and RNASEL may play a role in prostate cancer progression and severity.