Jay H Fowke

Vanderbilt University, Нашвилл, Michigan, United States

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Publications (87)375.32 Total impact

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    ABSTRACT: Many potentially modifiable risk factors for prostate cancer are also associated with prostate cancer screening, which may induce a bias in epidemiologic studies. We investigated the associations of body mass index (weight (kg)/height (m)(2)), smoking, and alcohol consumption with risk of fatal prostate cancer in Asian countries where prostate cancer screening is not widely utilized. Analysis included 18 prospective cohort studies conducted during 1963-2006 across 6 countries in southern and eastern Asia that are part of the Asia Cohort Consortium. Body mass index, smoking, and alcohol intake were determined by questionnaire at baseline, and cause of death was ascertained through death certificates. Analysis included 522,736 men aged 54 years, on average, at baseline. During 4.8 million person-years of follow-up, there were 634 prostate cancer deaths (367 prostate cancer deaths across the 11 cohorts with alcohol data). In Cox proportional hazards analyses of all cohorts in the Asia Cohort Consortium, prostate cancer mortality was not significantly associated with obesity (body mass index >25: hazard ratio (HR) = 1.08, 95% confidence interval (CI): 0.85, 1.36), ever smoking (HR = 1.00, 95% CI: 0.84, 1.21), or heavy alcohol intake (HR = 1.00, 95% CI: 0.74, 1.35). Differences in prostate cancer screening and detection probably contribute to differences in the association of obesity, smoking, or alcohol intake with prostate cancer risk and mortality between Asian and Western populations and thus require further investigation. © The Author 2015. Published by Oxford University Press on behalf of the Johns Hopkins Bloomberg School of Public Health. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.
    American journal of epidemiology 08/2015; 182(5). DOI:10.1093/aje/kwv089 · 5.23 Impact Factor
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    ABSTRACT: Prostate enlargement leading to clinical benign prostatic hyperplasia (BPH) is associated with metabolic dysregulation and obesity. The genetic basis of this association is unclear. Our objective was to evaluate whether single nucleotide polymorphisms (SNPs) previously associated with metabolic disorders are also associated with prostate volume (PV). Participants included 876 men referred for prostate biopsy and found to be prostate cancer free. PV was measured by transrectal ultrasound. Samples were genotyped using the Illumina Cardio-MetaboChip platform. Multivariable adjusted linear regression models were used to evaluate SNPs (additive coding) in relation to natural-log transformed (log) PV. We compared SNP-PV results from biopsy-negative men to 442 men with low-grade prostate cancer with similar levels of obesity and PV. Beta-coefficients from the discovery and replication samples were then aggregated with fixed effects inverse variance weighted meta-analysis. SNP rs11736129 (near the pseudo-gene LOC100131429) was significantly associated with log-PV (beta: 0.16, p-value 1.16x10-8) after adjusting for multiple testing. Other noteworthy SNPs that were nominally associated (p-value < 1x10-4) with log-PV included rs9583484 (intronic SNP in COL4A2), rs10146527 (intronic SNP in NRXN3), rs9909466 (SNP near RPL32P31), and rs2241606 (synonymous SNP in SLC12A7). We found several SNPs in metabolic loci associated with PV. Further studies are needed to confirm our results and elucidate the mechanism between these genetic loci, PV, and clinical BPH.
    PLoS ONE 07/2015; 10(7):e0132028. DOI:10.1371/journal.pone.0132028 · 3.23 Impact Factor
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    ABSTRACT: The study objective was to examine the role of physical activity (PA) and sedentary time (ST) on mortality risk among a population of low-income adults with diabetes. Black (n = 11,137) and white (n = 4508) men and women with diabetes from the Southern Community Cohort Study self-reported total PA levels and total ST. Participants were categorized into quartiles of total PA and total ST. Hazard ratios (HRs) and 95% confidence intervals (CIs) for subsequent mortality risk were estimated from Cox proportional hazards analysis with adjustment for potential confounders. During follow-up, 2370 participants died. The multivariable risk of mortality was lower among participants in the highest quartile of PA compared with those in the lowest quartile (HR, 0.64; 95% CI: 0.57-0.73). Mortality risk was significantly increased among participants in the highest compared with the lowest quartile of ST after adjusting for PA (HR, 1.21; 95% CI: 1.08-1.37). Across sex and race groups, similar trends of decreasing mortality with rising PA and increasing mortality with rising ST were observed. Although causality cannot be established from these observational data, the current findings suggest that increasing PA and decreasing ST may help extend survival among individuals with diabetes irrespective of race and sex. Copyright © 2015 Elsevier Inc. All rights reserved.
    Annals of Epidemiology 06/2015; 25(9). DOI:10.1016/j.annepidem.2015.04.006 · 2.00 Impact Factor
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    ABSTRACT: BACKGROUND Epidemiologic studies suggest that statin use may be inversely associated with risk of prostate cancer, but prior studies have focused predominantly on non-Hispanic white populations.METHODS We evaluated the association between statin use and prostate cancer risk in the Southern Community Cohort Study (SCCS). Study participants were 32,091 men aged 40–79 at baseline, 67% of whom were non-Hispanic black. Between study enrollment (2002–2009) and December 31, 2010, 570 prostate cancer cases were diagnosed, including 324 low-grade cancers (Gleason score <7 or Gleason pattern 3 + 4) and 107 high-grade cancers (Gleason score >7 or Gleason pattern 4 + 3). Analyses of overall prostate cancer were conducted using Cox regression and analyses of grade-specific cancer were conducted using competing risks models.RESULTSTen percent of non-Hispanic black men and 22% of non-Hispanic white men reported use of statins at study enrollment. As compared to non-use, statin use was associated with a non-significant 14% lower risk of prostate cancer in multivariable models (Hazard Ratio [HR]:0.86; 95% Confidence Interval [CI]: 0.63–1.18). This association was stronger for high-grade cancer (HR: 0.62; 95%CI: 0.30, 1.28) than low-grade cancer (HR:0.98; 95%CI: 0.65–1.48). Results were similar by race/ethnicity (p-interaction: 0.41) and did not vary by history of prostate-specific antigen [PSA] screening (p-interaction: 0.65).CONCLUSIONS Results suggest no strong association between statin use and prostate cancer risk overall, and further suggest that if a modest protective effect does exist, it does not vary by race/ethnicity and may be restricted to high-grade tumors, although power to detect differences by subgroup was limited. Prostate © 2015 Wiley Periodicals, Inc.
    The Prostate 05/2015; 75(13). DOI:10.1002/pros.23019 · 3.57 Impact Factor
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    ABSTRACT: High prevalence of lower urinary tract symptoms (LUTS) consistent with benign prostate hyperplasia (BPH) is associated with obesity and prostatic inflammation. Here, we investigated whether chemokines associated with obesity and prostatic inflammation can be measured in normally voided urine of BPH/LUTS patients to demonstrate the mechanistic association between obesity and BPH/LUTS. Frozen urine specimens of BPH/LUTS patients enrolled in the Nashville Men's Health Study were sent for blinded analysis to University of Pittsburgh. Thirty patients were blocked by their AUA-SI (>7 or ≤7) and prostatic enlargement (<40, 40-60, >60 cc). Clinical parameters including age, prostate size, and medications were derived from chart review. CXC chemokines (CXCL-1, CXCL-8, and CXCL-10), CC chemokines (CCL2 and CCL3), and sIL-1ra were measured in thawed urine using Luminex™ xMAP(®) technology and ELISA for NGF. Urinary CCL2 levels were several fold higher compared with the other six proteins, of which CCL3 was detectable in less than one-fourth of patients. Urine levels of sIL-1ra and CXCL-8 were significantly associated with increasing BMI and waist circumference in BPH patients. CXCL-8 showed a marginal association with overall AUA-SI scores, as well as obstructive (p = 0.08) symptom subscores. Prostate volume was inversely and marginally associated with urinary CXCL-10 (p = 0.09). Urine levels of CXCL-8, CXCL-10, and sIL-1ra were associated with varying degrees with LUTS severity, prostate size, and obesity, respectively. These findings in urine are consistent with past studies of chemokine levels from expressed prostatic secretions and demonstrate the potential of noninvasively measured chemokine in urine to objectively classify BPH/LUTS patients.
    International Urology and Nephrology 04/2015; 47(7). DOI:10.1007/s11255-015-0992-2 · 1.52 Impact Factor
  • The Journal of Urology 04/2015; 193(4):e831. DOI:10.1016/j.juro.2015.02.2399 · 4.47 Impact Factor
  • Cancer Research 10/2014; 74(19 Supplement):5064-5064. DOI:10.1158/1538-7445.AM2014-5064 · 9.33 Impact Factor
  • Jay H. Fowke · Saundra Motley · Susan Byerly
    Cancer Research 10/2014; 74(19 Supplement):2175-2175. DOI:10.1158/1538-7445.AM2014-2175 · 9.33 Impact Factor
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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.
    Cancer Epidemiology Biomarkers & Prevention 08/2014; 23(11). DOI:10.1158/1055-9965.EPI-14-0129 · 4.13 Impact Factor
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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; 180(4). DOI:10.1093/aje/kwu142 · 5.23 Impact Factor
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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 06/2014; 7(9). DOI:10.1158/1940-6207.CAPR-14-0075 · 4.44 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 05/2014; 74(6). DOI:10.1002/pros.22785 · 3.57 Impact Factor
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    ABSTRACT: 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.
    European Urology 04/2014; 66(6). DOI:10.1016/j.eururo.2014.01.037 · 13.94 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.
    Journal of the National Cancer Institute 03/2014; 106(4). DOI:10.1093/jnci/dju061 · 12.58 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. DOI:10.1186/1479-5868-11-12 · 4.11 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. DOI:10.1016/j.ajhg.2013.08.012 · 10.93 Impact Factor
  • T. Edwards · A. Giri · S. Motley · W. Duong · J. H. Fowke
    Cancer Epidemiology Biomarkers & Prevention 08/2013; 21(11_Supplement):45-45. DOI:10.1158/1055-9965.GWAS-45 · 4.13 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. DOI:10.1249/MSS.0b013e3182897690 · 3.98 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; 24(10). DOI:10.1007/s10552-013-0257-2 · 2.74 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 & Prevention 06/2013; 22(9). DOI:10.1158/1055-9965.EPI-13-0123 · 4.13 Impact Factor

Publication Stats

1k Citations
375.32 Total Impact Points


  • 2003–2015
    • Vanderbilt University
      • • Vanderbilt Epidemiology Center
      • • Division of Epidemiology
      • • Department of Medicine
      • • Vanderbilt-Ingram Cancer Center (VICC)
      Нашвилл, Michigan, United States
  • 2013
    • University of Massachusetts Amherst
      • Department of Kinesiology
      Amherst Center, Massachusetts, United States
  • 2011
    • Nashville Online
      Nashville, Michigan, United States