Jay H Fowke

Vanderbilt University, Nashville, Michigan, United States

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Publications (71)253.99 Total impact

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    ABSTRACT: Background: Multiple primary cancers account for ~16% of all incident cancers in the U.S.. While genome-wide association studies (GWAS) have identified many common genetic variants associated with various cancer sites, no study has examined the association of these genetic variants with risk of multiple primary cancers (MPC). Methods: As part of the NHGRI Population Architecture using Genomics and Epidemiology (PAGE) study, we used data from the Multiethnic Cohort and Women's Health Initiative. Incident MPC (IMPC) cases (n=1,385) were defined as participants diagnosed with >1 incident cancers after cohort entry. Participants diagnosed with only one incident cancer after cohort entry with follow-up equal to or longer than IMPC cases served as controls (single-index cancer controls; n= 9,626). Fixed-effects meta-analyses of unconditional logistic regression analyses were used to evaluate the association between cancer risk variants and IMPC risk. To account for multiple comparisons, we used the false positive report probability (FPRP) to determine statistical significance. Results: A nicotine dependence-associated and lung cancer variant, CHRNA3 rs578776 (OR=1.16, 95% CI=1.05-1.26; p=0.004) and two breast cancer variants, EMBP1 rs11249433 and TOX3 rs3803662 (OR=1.16, 95% CI=1.04-1.28; p=0.005 and OR=1.13, 95% CI=1.03-1.23; p=0.006) were significantly associated with risk of IMPC. The associations for rs578776 and rs11249433 remained (p<0.05) after removing subjects who had lung or breast cancers, respectively (p-values≤0.046). These associations did not show significant heterogeneity by smoking status (p-heterogeneity≥0.53). Conclusions: Our study has identified rs578776 and rs11249433 as risk variants for IMPC. Impact: These findings may help to identify genetic regions associated with IMPC risk.
    08/2014;
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    ABSTRACT: There is limited evidence demonstrating the benefits of physical activity with regard to mortality risk or the harms associated with sedentary behavior in black adults, so we examined the relationships between these health behaviors and cause-specific mortality in a prospective study that had a large proportion of black adults. Participants (40-79 years of age) enrolled in the Southern Community Cohort Study between 2002 and 2009 (n = 63,308) were prospectively followed over 6.4 years, and 3,613 and 1,394 deaths occurred in blacks and whites, respectively. Black adults who reported the highest overall physical activity level (≥32.3 metabolic equivalent-hours/day vs. <9.7 metabolic equivalent-hours/day) had lower risks of death from all causes (hazard ratio (HR) = 0.76. 95% confidence interval (CI): 0.69, 0.85), cardiovascular disease (HR = 0.81, 95% CI: 0.67, 0.98), and cancer (HR = 0.76, 95% CI: 0.62, 0.94). In whites, a higher physical activity level was associated with a lower risk of death from all causes (HR = 0.76, 95% CI: 0.64, 0.90) and cardiovascular disease (HR = 0.69, 95% CI: 0.49, 0.99) but not cancer (HR = 0.95, 95% CI: 0.67, 1.34). Spending more time being sedentary (>12 hours/day vs. <5.76 hours/day) was associated with a 20%-25% increased risk of all-cause mortality in blacks and whites. Blacks who reported the most time spent being sedentary (≥10.5 hours/day) and lowest level of physical activity (<12.6 metabolic equivalent-hours/day) had a greater risk of death (HR = 1.47, 95% CI: 1.25, 1.71). Our study provides evidence that suggests that health promotion efforts to increase physical activity level and decrease sedentary time could help reduce mortality risk in black adults.
    American journal of epidemiology. 08/2014;
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    ABSTRACT: NKX3.1 is an androgen-regulated prostate tumor suppressor protein. We previously found that antioxidant administration (N-acetylcysteine) in the Nkx3.1 knock-out mouse model promoted prostate epithelial proliferation, suggesting that NKX3.1 activity modifies the effect of antioxidant administration on prostate carcinogenesis. Interestingly, administration of the antioxidant vitamin E significantly increased prostate cancer risk in the Selenium and Vitamin E Cancer Prevention Trial (SELECT), suggesting our animal experiments may be relevant to humans. To determine whether NKX3.1 played a role in increased human prostate cancer risk associated with antioxidant administration in SELECT, we investigated the joint risk of antioxidant administration and NKX3.1 genotypes previously found to be associated with decreased NKX3.1 mRNA expression (rs11781886) or DNA-binding activity in vitro (rs2228013) in the SELECT biomarker case-cohort sub-study (1,866 cases; 3135 non-cases). Multivariable COX regression models were developed to determine the joint association of NKX3.1 genotypes with administration of vitamin E, selenium, or the combination, compared to placebo. The CC genotype at rs11781886 combined with selenium administration was associated with increased overall prostate cancer risk (HR 1.676, 95% CI 1.011-2.777, p=0.045) and low grade prostate cancer risk (HR 1.811, 95% CI 1.016-3.228, p=0.0441). Similarly, the rs11781886 minor allele (CC+CT) combined with vitamin E administration was significantly associated with increased prostate cancer risk (HR 1.450, 95% CI 1.117-1.882, p=0.0052). Our results indicate that variation in NKX3.1 expression combined with selenium or vitamin E treatment modifies the risk of prostate cancer. Genetic background may modulate the effects of antioxidant supplementation thought to act as chemoprevention agents.
    Cancer prevention research (Philadelphia, Pa.). 06/2014;
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    ABSTRACT: Background Although most studies found no association between alcohol intake and prostate cancer (PCa) risk, an analysis of the Prostate Cancer Prevention Trial found that high alcohol intake significantly increased PCa risk among men randomized to the 5α-reductase inhibitor (5-ARI) finasteride. Objective Determine whether alcohol affects PCa risk among men taking the 5-ARI dutasteride. Design, settings, and participants Reduction by Dutasteride of Prostate Cancer Events was a 4-yr, multicenter, randomized, double-blind, placebo-controlled trial to compare PCa after dutasteride administration (0.5 mg/d) with placebo. Participants had a baseline prostate-specific antigen between 2.5 and 10.0 ng/ml and a recent negative prostate biopsy. Alcohol intake was determined by baseline questionnaire, and participants underwent a prostate biopsy to determine PCa status at 2 yr and 4 yr of follow-up. Outcome measurements and statistical analysis Multivariable logistic regression was used to calculate odds ratios (ORs) and 95% confidence intervals (CIs) for the associations between alcohol intake and low-grade (Gleason <7) and high-grade (Gleason >7) PCa. Results and limitations Of 6374 participants in our analysis, approximately 25% reported no alcohol consumption, 49% were moderate drinkers (one to seven drinks per week), and 26% were heavy drinkers (more than seven drinks per week). Alcohol intake was not associated with low- or high-grade PCa in the placebo arm and was not associated with low-grade PCa among men taking dutasteride. In contrast, men randomized to dutasteride and reporting more than seven drinks per week were 86% more likely to be diagnosed with high-grade PCa (p = 0.01). Among alcohol abstainers, dutasteride was associated with significantly reduced risk of high-grade PCa (OR: 0.59; 95% CI, 0.38–0.90), but dutasteride was no longer associated with reduced high-grade PCa among men reporting high alcohol intake (OR: 0.99; 95% CI, 0.67–1.45). Conclusions Alcohol consumption negated a protective association between dutasteride and high-grade PCa. Patient summary We confirmed a prior study that alcohol affects PCa prevention in patients taking 5-ARIs. Patients taking 5-ARIs may wish to eliminate alcohol intake if they are concerned about PCa.
    European Urology 04/2014; · 10.48 Impact Factor
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    ABSTRACT: Genome-wide association studies have identified hundreds of genetic variants associated with specific cancers. A few of these risk regions have been associated with more than one cancer site; however, a systematic evaluation of the associations between risk variants for other cancers and lung cancer risk has yet to be performed. We included 18023 patients with lung cancer and 60543 control subjects from two consortia, Population Architecture using Genomics and Epidemiology (PAGE) and Transdisciplinary Research in Cancer of the Lung (TRICL). We examined 165 single-nucleotide polymorphisms (SNPs) that were previously associated with at least one of 16 non-lung cancer sites. Study-specific logistic regression results underwent meta-analysis, and associations were also examined by race/ethnicity, histological cell type, sex, and smoking status. A Bonferroni-corrected P value of 2.5×10(-5) was used to assign statistical significance. The breast cancer SNP LSP1 rs3817198 was associated with an increased risk of lung cancer (odds ratio [OR] = 1.10; 95% confidence interval [CI] = 1.05 to 1.14; P = 2.8×10(-6)). This association was strongest for women with adenocarcinoma (P = 1.2×10(-4)) and not statistically significant in men (P = .14) with this cell type (P het by sex = .10). Two glioma risk variants, TERT rs2853676 and CDKN2BAS1 rs4977756, which are located in regions previously associated with lung cancer, were associated with increased risk of adenocarcinoma (OR = 1.16; 95% CI = 1.10 to 1.22; P = 1.1×10(-8)) and squamous cell carcinoma (OR = 1.13; CI = 1.07 to 1.19; P = 2.5×10(-5)), respectively. Our findings demonstrate a novel pleiotropic association between the breast cancer LSP1 risk region marked by variant rs3817198 and lung cancer risk.
    CancerSpectrum Knowledge Environment 03/2014; · 14.07 Impact Factor
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    ABSTRACT: Approximately one-third of patients fail medical treatment for benign prostatic hyperplasia and associated lower urinary tract symptoms (BPH/LUTS) requiring surgical intervention. Our purpose was to establish a molecular characterization for patients undergoing surgical intervention for LUTS to address therapeutic deficiencies. Clinical, molecular, and histopathological profiles were analyzed in 26 patients undergoing surgery for severe LUTS. Incidental transitional zone nodules were isolated from 37 patients with mild symptoms undergoing radical prostatectomy. Clinical parameters including age, prostate volume, medication, prostate specific antigen, symptom score, body mass index, and incidence of diabetes were collected. Multivariate logistic regression analysis with adjustments for potential confounding variables was used to examine associations between patient clinical characteristics and molecular targets identified through molecular profiling. Compared to incidental BPH, progressive symptomatic BPH was associated with increased expression of the activating protein-1 transcription factor/chemokine network. As expected, inverse correlations were drawn between androgen receptor levels and age, as well as between 5α-reductase inhibitor (5ARI) treatment and tissue prostate specific antigen levels; however, a novel association was also drawn between 5ARI treatment and increased c-FOS expression. This study provides molecular evidence that a network of pro-inflammatory activating protein-1 transcription factors and associated chemokines are highly enriched in symptomatic prostate disease, a profile that molecularly categorizes with many other chronic autoimmune diseases. Because 5ARI treatment was associated with increased c-FOS expression, future studies should explore whether increased activating protein-1 proteins are causal factors in the development of symptomatic prostate disease, inflammation or resistance to traditional hormonal therapy. Prostate. © 2014 Wiley Periodicals, Inc.
    The Prostate 02/2014; · 3.84 Impact Factor
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    ABSTRACT: Purpose: Gathering contextual information (i.e., location and purpose) about active and sedentary behaviors is an advantage of self-report tools such as previous day recalls (PDR). However, the validity of PDR's for measuring context has not been empirically tested. The purpose of this paper was to compare PDR estimates of location and purpose to direct observation (DO). Fifteen adult (18-75 y) and 15 adolescent (12-17 y) participants were directly observed during at least one segment of the day (i.e., morning, afternoon or evening). Participants completed their normal daily routine while trained observers recorded the location (i.e., home, community, work/school), purpose (e.g., leisure, transportation) and whether the behavior was sedentary or active. The day following the observation, participants completed an unannounced PDR. Estimates of time in each context were compared between PDR and DO. Intra-class correlations (ICC), percent agreement and Kappa statistics were calculated. For adults, percent agreement was 85% or greater for each location and ICC values ranged from 0.71 to 0.96. The PDR-reported purpose of adults' behaviors were highly correlated with DO for household activities and work (ICCs of 0.84 and 0.88, respectively). Transportation was not significantly correlated with DO (ICC = -0.08). For adolescents, reported classification of activity location was 80.8% or greater. The ICCs for purpose of adolescents' behaviors ranged from 0.46 to 0.78. Participants were most accurate in classifying the location and purpose of the behaviors in which they spent the most time. This study suggests that adults and adolescents can accurately report where and why they spend time in behaviors using a PDR. This information on behavioral context is essential for translating the evidence for specific behavior-disease associations to health interventions and public policy.
    International Journal of Behavioral Nutrition and Physical Activity 02/2014; 11(1):12. · 3.58 Impact Factor
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    ABSTRACT: Genome-wide association studies (GWASs) primarily performed in European-ancestry (EA) populations have identified numerous loci associated with body mass index (BMI). However, it is still unclear whether these GWAS loci can be generalized to other ethnic groups, such as African Americans (AAs). Furthermore, the putative functional variant or variants in these loci mostly remain under investigation. The overall lower linkage disequilibrium in AA compared to EA populations provides the opportunity to narrow in or fine-map these BMI-related loci. Therefore, we used the Metabochip to densely genotype and evaluate 21 BMI GWAS loci identified in EA studies in 29,151 AAs from the Population Architecture using Genomics and Epidemiology (PAGE) study. Eight of the 21 loci (SEC16B, TMEM18, ETV5, GNPDA2, TFAP2B, BDNF, FTO, and MC4R) were found to be associated with BMI in AAs at 5.8 × 10(-5). Within seven out of these eight loci, we found that, on average, a substantially smaller number of variants was correlated (r(2) > 0.5) with the most significant SNP in AA than in EA populations (16 versus 55). Conditional analyses revealed GNPDA2 harboring a potential additional independent signal. Moreover, Metabochip-wide discovery analyses revealed two BMI-related loci, BRE (rs116612809, p = 3.6 × 10(-8)) and DHX34 (rs4802349, p = 1.2 × 10(-7)), which were significant when adjustment was made for the total number of SNPs tested across the chip. These results demonstrate that fine mapping in AAs is a powerful approach for both narrowing in on the underlying causal variants in known loci and discovering BMI-related loci.
    The American Journal of Human Genetics 10/2013; 93(4):661-671. · 11.20 Impact Factor
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    ABSTRACT: A previous-day recall (PDR) may be a less error-prone alternative to traditional questionnaire-based estimates of physical activity and sedentary behavior (e.g., past year), but the validity of the method is not established. We evaluated the validity of an interviewer administered PDR in adolescents (12-17 yr) and adults (18-71 yr). In a 7-d study, participants completed three PDR, wore two activity monitors, and completed measures of social desirability and body mass index. PDR measures of active and sedentary time was contrasted against an accelerometer (ActiGraph) by comparing both to a valid reference measure (activPAL) using measurement error modeling and traditional validation approaches. Age- and sex-specific mixed models comparing PDR to activPAL indicated the following: 1) there was a strong linear relationship between measures for sedentary (regression slope, β1 = 0.80-1.13) and active time (β1 = 0.64-1.09), 2) person-specific bias was lower than random error, and 3) correlations were high (sedentary: r = 0.60-0.81; active: r = 0.52-0.80). Reporting errors were not associated with body mass index or social desirability. Models comparing ActiGraph to activPAL indicated the following: 1) there was a weaker linear relationship between measures for sedentary (β1 = 0.63-0.73) and active time (β1 = 0.61-0.72), (2) person-specific bias was slightly larger than random error, and (3) correlations were high (sedentary: r = 0.68-0.77; active: r = 0.57-0.79). Correlations between the PDR and the activPAL were high, systematic reporting errors were low, and the validity of the PDR was comparable with the ActiGraph. PDR may have value in studies of physical activity and health, particularly those interested in measuring the specific type, location, and purpose of activity-related behaviors.
    Medicine and science in sports and exercise 08/2013; 45(8):1629-1638. · 4.48 Impact Factor
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    ABSTRACT: Prior studies conducted primarily among white men find a reduced risk of prostate cancer associated with time since developing diabetes. While biologic explanations are plausible, the association may in part arise from more frequent prostate cancer screening among those with a diabetes diagnosis. The purpose of the present study was to investigate the association between diabetes and prostate cancer screening. We examined differences in prostate cancer screening (prostate-specific antigen and/or digital rectal examination) testing practices after a diabetes diagnosis among lower-income persons living in the southeastern United States and enrolled in the Southern Community Cohort Study between 2002 and 2009. Baseline in-person interviews collected information on history of diabetes and prostate cancer screening from 18,809 black and 6,404 white men aged 40-79 years. After adjustment for confounding, diabetic black [odds ratio (OR) 1.12, 95 % confidence interval (CI) 1.01-1.25] and white (OR 1.25, 95 % CI 1.03-1.51) men were more likely to undergo recent prostate cancer screening compared to non-diabetic men of the same race. The increased risk for prostate cancer screening, however, occurred primarily within the first 12 months after diabetes diagnosis. Our results suggest that a diabetes diagnosis modestly increases the likelihood of having a prostate cancer screening test for both black and white men. The prevalence of screening was higher nearer to the time of diabetes diagnosis, which may contribute to an early increase in prostate cancer detection followed by lower prostate cancer detection after an extended time.
    Cancer Causes and Control 07/2013; · 3.20 Impact Factor
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    ABSTRACT: Background: To address inconsistent findings of obesity and prostate cancer risk, we analyzed the association between prostate cancer (PC) and genetic markers of obesity and metabolism. Methods: Analyses included 176,520 single nucleotide polymorphisms (SNPs) associated with 23 metabolic traits. We examined the association between SNPs and PC in 871 cases and 906 controls, including 427 high-grade cases with Gleason≥7. Genetic risk scores (GRSs) for body mass index (BMI) and waist-to-hip ratio (WHR) were also created by summing alleles associated with increasing BMI or WHR. Results: PC was associated with 5 loci, including cyclin M2, with p-values less than 1x10-4. In addition, the WHR GRS was associated with high-grade PC versus controls (OR: 1.05; 95% CI: 1.00 - 1.11, p-value = 0.048), and high-grade PC versus low-grade PC (OR: 1.07, 95% CI 1.01 - 1.13, p-value = 0.03). None of these findings exceed the threshold for significance after correction for multiple testing. Conclusions: Variants in genes known to be associated with metabolism and obesity may be associated with PC. We show evidence for pleiotropy between WHR GRS and PC. This finding is consistent with the function of several WHR genes, and previously described relationships with cancer traits. Impact: Limitations in standard obesity measures suggest alternative characterizations of obesity may be needed to understand the role of metabolic dysregulation in PC. The underlying genetics of WHR or other Metabochip SNPs, while not statistically significant beyond multiple testing thresholds, support the metabolic hypothesis of prostate carcinogenesis and warrant further investigation in independent samples.
    Cancer Epidemiology Biomarkers &amp Prevention 06/2013; · 4.56 Impact Factor
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    ABSTRACT: BACKGROUND: Follow-through of a positive screening test is necessary to reap the potential benefits of cancer screening. Racial variation in follow-through diagnostic care may underlie a proportion of the known disparity in prostate cancer mortality. The authors used data from the screening arm of the Prostate, Lung, Colorectal, and Ovarian (PLCO) cancer screening trial to determine whether race is associated with the use of follow-up diagnostic testing after a positive initial screening evaluation. METHODS: Men who had a prostate-specific antigen (PSA) level >4 ng/mL at any time during the study were included. The proportion of men who underwent follow-up evaluation with a repeat PSA, a prostate biopsy, or either test within 9 months was determined, and the authors tested for differences in follow-through according to race using mixed-effects multivariate models with a random effect for accrual site to account for clustering. Models were stratified according to age (<65 years and ≥65 years). RESULTS: Among 6294 men who had a PSA elevation during the study period, 70% underwent a repeat PSA or prostate biopsy within 9 months. Non-Hispanic black men aged <65 years had 45% lower odds of undergoing a repeat PSA test or prostate biopsy compared with non-Hispanic white men (odds ratio, 0.55; 95% confidence interval, 0.37-0.82), whereas there was no racial difference in follow-through among older men. CONCLUSIONS: The current results suggest that limitations in access to care among non-Hispanic black men under the age of Medicare eligibility may underlie the paradoxically low use of follow-through diagnostic care among non-Hispanic black men in the United States. Cancer 2013. © 2013 American Cancer Society.
    Cancer 04/2013; · 5.20 Impact Factor
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    ABSTRACT: OBJECTIVE: Several genome-wide association studies (GWAS) have demonstrated that common genetic variants contribute to obesity. However, studies of this complex trait have focused on ancestrally European populations, despite the high prevalence of obesity in some minority groups. DESIGN AND METHODS: As part of the "Population Architecture using Genomics and Epidemiology (PAGE)" Consortium, we investigated the association between 13 GWAS-identified single-nucleotide polymorphisms (SNPs) and BMI and obesity in 69,775 subjects, including 6,149 American Indians, 15,415 African-Americans, 2,438 East Asians, 7,346 Hispanics, 604 Pacific Islanders, and 37,823 European Americans. For the BMI-increasing allele of each SNP, we calculated β coefficients using linear regression (for BMI) and risk estimates using logistic regression (for obesity defined as BMI ≥ 30) followed by fixed-effects meta-analysis to combine results across PAGE sites. Analyses stratified by racial/ethnic group assumed an additive genetic model and were adjusted for age, sex, and current smoking. We defined "replicating SNPs" (in European Americans) and "generalizing SNPs" (in other racial/ethnic groups) as those associated with an allele frequency-specific increase in BMI. RESULTS: By this definition, we replicated 9/13 SNP associations (5 out of 8 loci) in European Americans. We also generalized 8/13 SNP associations (5/8 loci) in East Asians, 7/13 (5/8 loci) in African Americans, 6/13 (4/8 loci) in Hispanics, 5/8 in Pacific Islanders (5/8 loci), and 5/9 (4/8 loci) in American Indians. CONCLUSION: Linkage disequilibrium patterns suggest that tagSNPs selected for European Americans may not adequately tag causal variants in other ancestry groups. Accordingly, fine-mapping in large samples is needed to comprehensively explore these loci in diverse populations.
    Obesity 04/2013; 21(4):835-846. · 3.92 Impact Factor
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    ABSTRACT: BACKGROUND: Although smoking behavior is known to affect body mass index (BMI), the potential for smoking to influence genetic associations with BMI is largely unexplored. METHODS: As part of the 'Population Architecture using Genomics and Epidemiology (PAGE)' Consortium, we investigated interaction between genetic risk factors associated with BMI and smoking for 10 single nucleotide polymorphisms (SNPs) previously identified in genome-wide association studies. We included 6 studies with a total of 56,466 subjects (16,750 African Americans (AA) and 39,716 European Americans (EA)). We assessed effect modification by testing an interaction term for each SNP and smoking (current vs. former/never) in the linear regression and by stratified analyses. RESULTS: We did not observe strong evidence for interactions and only observed two interactions with p-values <0.1: for rs6548238/TMEM18, the risk allele (C) was associated with BMI only among AA females who were former/never smokers (beta = 0.018, p = 0.002), vs. current smokers (beta = 0.001, p = 0.95, pinteraction = 0.10). For rs9939609/FTO, the A allele was more strongly associated with BMI among current smoker EA females (beta = 0.017, p = 3.5x10-5), vs. former/never smokers (beta = 0.006, p = 0.05, pinteraction = 0.08). CONCLUSIONS: These analyses provide limited evidence that smoking status may modify genetic effects of previously identified genetic risk factors for BMI. Larger studies are needed to follow up our results.Clinical Trial Registration: NCT00000611.
    BMC Medical Genetics 01/2013; 14(1):6. · 2.54 Impact Factor
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    ABSTRACT: Evidence is limited as to whether heritable risk of obesity varies throughout adulthood. Among >34,000 European Americans, aged 18-100 years, from multiple U.S. studies in the Population Architecture of Genomics and Epidemiology Consortium, we examined evidence for heterogeneity in the associations of five established obesity risk variants (near FTO, GNPDA2, MTCH2, TMEM18, and NEGR1) with BMI across four distinct epochs of adulthood: 1) young adulthood (ages 18-25 years), adulthood (ages 26-49 years), middle-age adulthood (ages 50-69 years), and older adulthood (ages ≥70 years); or 2) by menopausal status in women and stratification by age 50 years in men. Summary-effect estimates from each meta-analysis were compared for heterogeneity across the life epochs. We found heterogeneity in the association of the FTO (rs8050136) variant with BMI across the four adulthood epochs (P = 0.0006), with larger effects in young adults relative to older adults (β [SE] = 1.17 [0.45] vs. 0.09 [0.09] kg/m(2), respectively, per A allele) and smaller intermediate effects. We found no evidence for heterogeneity in the association of GNPDA2, MTCH2, TMEM18, and NEGR1 with BMI across adulthood. Genetic predisposition to obesity may have greater effects on body weight in young compared with older adulthood for FTO, suggesting changes by age, generation, or secular trends. Future research should compare and contrast our findings with results using longitudinal data.
    Diabetes 01/2013; · 7.90 Impact Factor
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    ABSTRACT: Prostate enlargement is common with aging and obesity. We investigated the association between obesity and prostate cancer controlling for differential detection related to prostate enlargement. In an analysis of 500 men, we found body mass index, waist-hip ratio, and blood leptin levels were significantly associated with high-grade PC, but only among men without prostate enlargement. Leptin was also significantly associated with high-grade prostatic intraepithelial neoplasia (HGPIN) in the absence of prostate enlargement. Our results suggest obesity advances prostate carcinogenesis, and that detection biases at prostate biopsy may explain past inconsistencies in the association between obesity and PC.
    Cancer letters 10/2012; · 5.02 Impact Factor
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    ABSTRACT: Difference in the quality of care may contribute to the less optimal prostate cancer treatment outcomes among black men compared with white men. We determined whether a racial quality of care gap exists in surgical care for prostate cancer, as evidenced by racial variation in the use of high volume surgeons and facilities, and in the quality of certain outcome measures of care. We performed cross-sectional and cohort analyses of administrative data from the Healthcare Cost and Utilization Project all-payer State Inpatient Databases, encompassing all nonfederal hospitals in Florida, Maryland and New York State from 1996 to 2007. Included in analysis were men 18 years old or older with a diagnosis of prostate cancer who underwent radical prostatectomy. We compared the use of surgeons and/or hospitals in the top quartile of annual volume for this procedure, inpatient blood transfusion, complications, mortality and length of stay between black and white patients. Of 105,972 patients 81,112 (76.5%) were white, 14,006 (13.2%) were black, 6,999 (6.6%) were Hispanic and 3,855 (3.6%) were all other. In mixed effects multivariate models, black men had markedly lower use of high volume hospitals (OR 0.73, 95% CI 0.70-0.76) and surgeons (OR 0.67, 95% CI 0.64-0.70) compared to white men. Black men also had higher odds of blood transfusion (OR 1.08, 95% CI 1.01-1.14), longer length of stay (OR 1.07, 95% CI 1.06-1.07) and inpatient mortality (OR 1.73, 95% CI 1.02-2.92). Using an all-payer data set, we identified concerning potential quality of care gaps between black and white men undergoing radical prostatectomy for prostate cancer.
    The Journal of urology 08/2012; 188(4):1279-85. · 3.75 Impact Factor
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    ABSTRACT: Low physical activity (PA) is linked to cancer and other diseases prevalent in racial/ethnic minorities and low-income populations. This study evaluated the PA questionnaire (PAQ) used in the Southern Cohort Community Study, a prospective investigation of health disparities between African-American and white adults. The PAQ was administered upon entry into the cohort (PAQ1) and after 12-15 months (PAQ2) in 118 participants (40-60 year-old, 48% male, 74% African-American). Test-retest reliability (PAQ1 versus PAQ2) was assessed using Spearman correlations and the Wilcoxon signed rank test. Criterion validity of the PAQ was assessed via comparison with a PA monitor and a last-month PA survey (LMPAS), administered up to 4 times in the study period. The PAQ test-retest reliability ranged from 0.25-0.54 for sedentary behaviors and 0.22-0.47 for active behaviors. The criterion validity for the PAQ compared with PA monitor ranged from 0.21-0.24 for sedentary behaviors and from 0.17-0.31 for active behaviors. There was general consistency in the magnitude of correlations between the PAQ and PA-monitor between African-Americans and whites. The SCCS-PAQ has fair to moderate test-retest reliability and demonstrated some evidence of criterion validity for ranking participants by their level of sedentary and active behaviors.
    Journal of Physical Activity and Health 08/2012; 9(6):765-75. · 1.95 Impact Factor
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    ABSTRACT: Study Type - Aetiology (case series) Level of Evidence 4 What's known on the subject? and What does the study add? Greater leisure-time physical activity (PA) levels or a lower body mass index have previously been associated with a lower risk of benign prostatic hyperplasia or less severe lower urinary tract symptoms (LUTS). However, separating the effects of PA from obesity can be difficult, and the types of PA and the mechanisms underlying any association with LUTS among older men are unclear. The present analysis used multiple validated instruments to measure PA domains across workplace, leisure time, and home domains, and finds that PAs ranging from sports to light housework are associated with lower LUTS severity. The benefits of PA were seen with irritative symptoms, and also among obese men. Furthermore, this analysis begins the investigation of mechanism by finding that the relationship between PA and LUTS is not mediated by prostate enlargement. OBJECTIVES: •  To determine the association between lower urinary tract symptoms (LUTS) severity and physical activity (PA) across workplace, home, and leisure domains. •  To determine the mediating role of prostate enlargement on LUTS severity and PA. PATIENTS AND METHODS: •  The study included 405 men without prostate cancer or prostatic intraepithelial neoplasia. •  LUTS severity was ascertained using the American Urological Association Symptom Index and prostate size by ultrasonography. •  PA was assessed using validated questionnaires, with conversion to metabolic equivalent of task (MET)-h/week to estimate leisure-time PA energy expenditure. •  Analysis used multivariable linear regression, controlling for body mass index (BMI), age, race, and treatment for benign prostatic hyperplasia, cardiovascular disease and diabetes. RESULTS: •  Higher leisure-time PA energy expenditure and light housework activities were significantly associated with lower LUTS severity. •  Prostate volume was not significantly associated with PA in adjusted analyses, and controlling for prostate volume did not affect the association between LUTS severity and PA. •  Stratification by BMI showed a moderate interaction (P= 0.052), suggesting that PA was more strongly associated with LUTS severity among obese men. CONCLUSIONS: •  In this cross-sectional analysis, leisure-time and home-time PA was inversely associated with LUTS severity. •  The association between PA and LUTS severity was stronger for irritative symptoms and among obese men, and was not mediated through changes in prostate size. •  Our results indicate the need for further detailed investigation of PA and LUTS.
    BJU International 06/2012; · 3.05 Impact Factor
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    ABSTRACT: Leptin may be an important link between obesity and many high-burden diseases, including cancer and cardiovascular disease, but leptin levels and correlates in individuals of diverse racial backgrounds have not been well characterized despite racial differences in incidence and mortality patterns for many obesity-related diseases. In a cross-sectional study of 915 white and 892 black women enrolled in the Southern Community Cohort Study (age 40-79 years, half postmenopausal), serum leptin levels were compared between the race groups and across categories of body mass index (BMI). Potential correlates of leptin were assessed via race-stratified linear regression models. Blacks had higher unadjusted leptin levels than whites (geometric mean 22.4 vs. 19.0 ng/ml; p < 0.0001). Leptin increased with increasing BMI, and racial differences in leptin were most pronounced in women with BMI ≥25. Significant correlates of leptin included BMI, age, alcohol consumption, cigarette smoking, diabetes (both races) and fat consumption (black women only). Leptin remained higher in black women (22.7 vs. 18.8 ng/ml) after adjustment for these factors. Persistent racial differences in leptin concentrations exist after adjustment for BMI and other factors. Leptin assessment may be informative in future studies that investigate racial differences in the development of obesity-related diseases.
    Annals of Nutrition and Metabolism 02/2012; 60(2):90-7. · 1.66 Impact Factor

Publication Stats

815 Citations
253.99 Total Impact Points

Institutions

  • 2003–2014
    • Vanderbilt University
      • • Division of Epidemiology
      • • Department of Medicine
      • • Vanderbilt Epidemiology Center
      • • Vanderbilt-Ingram Cancer Center (VICC)
      Nashville, Michigan, United States
  • 2013
    • Fred Hutchinson Cancer Research Center
      • Division of Public Health Sciences
      Seattle, WA, United States
  • 2011
    • Nashville Online
      Nashville, Michigan, United States
    • University of North Carolina at Chapel Hill
      • Department of Epidemiology
      Chapel Hill, NC, United States
  • 2010
    • University of Iowa
      • Department of Urology
      Iowa City, IA, United States
    • Roswell Park Cancer Institute
      • Department of Urology
      Buffalo, NY, United States
  • 2001
    • University of South Carolina
      • Department of Epidemiology & Biostatistics
      Columbia, SC, United States
  • 2000
    • University of Massachusetts Medical School
      • Division of Preventive and Behavioral Medicine
      Worcester, MA, United States