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Newschaffer C.J.,Drexel University | Hoffman-Bolton J.,George mstock Center For Public Health Research And Prevention | Rifai N.,Childrens Hospital Boston | Visvanathan K.,Johns Hopkins Sidney Kimmel Comprehensive Cancer Center
Cancer Epidemiology Biomarkers and Prevention | Year: 2013

Obesity is a known risk factor for postmenopausal breast cancer; it has been postulated that adipocytokines may mediate this association. We explored the relationship between three markers altered by obesity: leptin, adiponectin, and soluble tumor necrosis factor receptor 2 (sTNF-R2), an inflammatory marker, with breast cancer risk in postmenopausal women. A nested case-control study of postmenopausal women was conducted within CLUE II, a prospective population-based cohort. Baseline plasma levels of leptin, adiponectin, and sTNF-R2 were assayed in 272 female breast cancer cases and 272 controls matched on age, date, and hour of blood draw. Conditional logistic regression was used to estimate matched odds ratios (OR) and 95% confidence intervals (CI). sTNF-R2 and leptin were independently positively associated with breast cancer risk in adjusted models. The OR for breast cancer comparing the highest to lowest tertile was 2.44 (95% CI: 1.30-4.58) for sTNFR2 and 1.98 (95% CI: 1.20-3.29) for leptin. While higher levels of adiponectin were protective (OR for the lowest tertile = 1.63; 95% CI: 1.02-2.60), there was no dose response. A 20% reduction in the breast cancer risk associated with overweight/obesity was observed when sTNF-R2 alone was included in multivariable models. Including both sTNF-R2 and adiponectin in the models resulted in a 29% reduction in the OR. Adipocytokines and sTNF-R2 are important factors in the etiology of postmenopausal breast cancer due to adiposity. This study informs our understanding of the relationship between obesity, inflammation, and postmenopausal breast cancer and identifies potential biomarkers. ©2013 AACR.

Alberg A.J.,Medical University of South Carolina | Jorgensen T.J.,Georgetown University | Ruczinski I.,Johns Hopkins University | Wheless L.,Medical University of South Carolina | And 12 more authors.
Carcinogenesis | Year: 2013

The hypothesis that germ-line polymorphisms in DNA repair genes influence cancer risk has previously been tested primarily on a cancer site-specific basis. The purpose of this study was to test the hypothesis that DNA repair gene allelic variants contribute to globally elevated cancer risk by measuring associations with risk of all cancers that occurred within a population-based cohort. In the CLUE II cohort study established in 1989 in Washington County, MD, this study was comprised of all 3619 cancer cases ascertained through 2007 compared with a sample of 2296 with no cancer. Associations were measured between 759 DNA repair gene single nucleotide polymorphisms (SNPs) and risk of all cancers. A SNP in O6-methylguanine-DNA methyltransferase, MGMT, (rs2296675) was significantly associated with overall cancer risk [per minor allele odds ratio (OR) 1.30, 95% confidence interval (CI) 1.19-1.43 and P-value: 4.1 ? 10-8]. The association between rs2296675 and cancer risk was stronger among those aged ≤54 years old than those who were ≥55 years at baseline (P-for-interaction = 0.021). OR were in the direction of increased risk for all 15 categories of malignancies studied (P < 0.0001), ranging from 1.22 (P = 0.42) for ovarian cancer to 2.01 (P = 0.008) for urinary tract cancers; the smallest P-value was for breast cancer (OR 1.45, P = 0.0002). The results indicate that the minor allele of MGMT SNP rs2296675, a common genetic marker with 37% carriers, was significantly associated with increased risk of cancer across multiple tissues. Replication is needed to more definitively determine the scientific and public health significance of this observed association. © The Author 2012. Published by Oxford University Press. All rights reserved.

Clipp S.L.,George mstock Center For Public Health Research And Prevention | Helzlsouer K.J.,George mstock Center For Public Health Research And Prevention | Helzlsouer K.J.,Prevention and Research Center | Helzlsouer K.J.,Johns Hopkins Medical Institutions | And 2 more authors.
Cancer Causes and Control | Year: 2010

Statin drugs appear to protect against advanced and possibly high-grade prostate cancer, perhaps through cholesterol-lowering. Thus, we evaluated the association between plasma cholesterol and prostate cancer. We conducted a prospective study in the CLUE II cohort of Washington County, MD. Included were 6,816 male county residents aged 35+ years old who did not have a cancer diagnosis at baseline in 1989. Plasma cholesterol, measured enzymatically at baseline, was categorized by clinical cutpoints. Cox proportional hazards regression was used to estimate multivariable-adjusted hazard ratios (HR) and 95% confidence intervals (CI) for total (n = 438) and high-grade (Gleason sum ≥7, n = 137) prostate cancer. Compared to men with high cholesterol (≥240 mg/dl), men with desirable (<200 mg/dl) or borderline (200 to <240 mg/dl) levels were less likely to develop high-grade prostate cancer, particularly when restricting to organ-confined cases (HR: 0.68, 95% CI 0.40-1.18; P trend = 0.12) and among men with higher BMI (HR: 0.36, 95% CI 0.16-0.79; P trend = 0.02). Results were unchanged after excluding cholesterol-lowering drug users. Cholesterol was not associated with total prostate cancer. Our study supports two prior ones suggesting that cholesterol influences risk of high-grade prostate cancer, and indirectly supports the hypothesis that cholesterol-lowering is a mechanism by which statins are protective. © 2009 Springer Science+Business Media B.V.

Brancati F.L.,Johns Hopkins University | Pollak M.N.,McGill University | Rifai N.,Harvard University | Clipp S.L.,George mstock Center For Public Health Research And Prevention | And 5 more authors.
Cancer Causes and Control | Year: 2010

Background: Metabolic syndrome components have been associated with colorectal cancer in several studies; however, evidence for colorectal adenomas is limited. Thus, we evaluated the association between markers of the metabolic syndrome with colorectal adenoma development in a nested case-control study. Methods: Colorectal adenoma cases (n = 132) and matched controls, who had a negative sigmoidoscopy or a colonoscopy (n = 260), were identified between baseline in 1989 and 2000 among participants in the CLUE II cohort of Washington County, Maryland. Concentrations of C-peptide, insulin-like growth factor binding protein-1, glycosylated hemoglobin, total cholesterol, high-density lipoprotein cholesterol, and triglycerides were measured in baseline blood specimens. Body mass index was calculated using baseline height and weight. Use of medications to treat diabetes mellitus was self-reported at baseline. Blood pressure was measured at baseline. Distributional cutpoints of the latter markers were used to define the metabolic syndrome components (hyperinsulinemia, hyperglycemia, obesity, dyslipidemia, and hypertension) present at baseline. Results: No statistically significant associations with adenomas were observed for the markers of the metabolic syndrome, with the exception of a strong positive association for use of diabetes medications (OR, 8.00; 95% CI, 1.70-37.67), albeit based on small numbers. Conclusion: Our findings do not support that components of the metabolic syndrome influence risk of colorectal adenomas, except possibly for severe diabetes mellitus warranting medical treatment. © 2009 Springer Science+Business Media B.V.

PubMed | Danish Cancer Society, George mstock Center for Public Health Research and Prevention, German Institute of Human Nutrition, U.S. National Cancer Institute and 26 more.
Type: Journal Article | Journal: The American journal of clinical nutrition | Year: 2015

Individual studies have suggested that circulating carotenoids, retinol, or tocopherols may be associated with prostate cancer risk, but the studies have not been large enough to provide precise estimates of associations, particularly by stage and grade of disease.The objective of this study was to conduct a pooled analysis of the associations of the concentrations of 7 carotenoids, retinol, -tocopherol, and -tocopherol with risk of prostate cancer and to describe whether any associations differ by stage or grade of the disease or other factors.Principal investigators of prospective studies provided individual participant data for prostate cancer cases and controls. Risk by study-specific fifths of each biomarker was estimated by using multivariable-adjusted conditional logistic regression in matched case-control sets.Data were available for up to 11,239 cases (including 1654 advanced stage and 1741 aggressive) and 18,541 controls from 15 studies. Lycopene was not associated with overall risk of prostate cancer, but there was statistically significant heterogeneity by stage of disease, and the OR for aggressive disease for the highest compared with the lowest fifth of lycopene was 0.65 (95% CI: 0.46, 0.91; P-trend = 0.032). No other carotenoid was significantly associated with overall risk of prostate cancer or with risk of advanced-stage or aggressive disease. For retinol, the OR for the highest compared with the lowest fifth was 1.13 (95% CI: 1.04, 1.22; P-trend = 0.015). For -tocopherol, the OR for the highest compared with the lowest fifth was 0.86 (95% CI: 0.78, 0.94; P-trend < 0.001), with significant heterogeneity by stage of disease; the OR for aggressive prostate cancer was 0.74 (95% CI: 0.59, 0.92; P-trend = 0.001). -Tocopherol was not associated with risk.Overall prostate cancer risk was positively associated with retinol and inversely associated with -tocopherol, and risk of aggressive prostate cancer was inversely associated with lycopene and -tocopherol. Whether these associations reflect causal relations is unclear.

PubMed | University of Ioannina, University of Houston, Harvard University and George mstock Center For Public Health Research And Prevention
Type: Journal Article | Journal: Cancer causes & control : CCC | Year: 2015

The association between prediagnostic interleukin-6 (IL-6) concentrations and risk of colorectal cancer was evaluated in a nested case-control study and a meta-analysis of prospective studies.Colorectal cancer cases (n = 173) and matched controls (n = 345) were identified between 1989 and 2000 among participants in the CLUE II cohort of Washington Country, Maryland. Matched odds ratios and the corresponding 95 % confidence intervals (CIs) were estimated using conditional logistic regression models.Participants in the highest third of plasma IL-6 concentration had a 2.48 times higher risk of colon cancer compared to participants in the bottom third (95 % CI 1.26-4.87; p-trend 0.02) after multivariate adjustment. This association did not differ according to the stage of disease, age, sex, or other potential modifying variables and remained statistically significant after adjustment for C-reactive protein concentrations. No statistically significant association was observed for rectal cancer risk. The meta-analysis of six prospective studies yielded an increased but borderline statistically significant risk of colon cancer per 1 U increase in naturally logarithm-transformed IL-6 (summary RR 1.22; 95 % CI 1.00-1.49; I (2) 46 %). An inverse association was noted for rectal cancer (RR 0.69; 95 % CI 0.54-0.88; I (2) 0 %), but there was evidence for small-study effects (p 0.02).Our findings provide support for a modest positive association between IL-6 concentrations and colon cancer risk. More work is needed to determine whether IL-6 is a valid marker of colorectal inflammation and whether such inflammation contributes to colon and rectal cancer risk.

PubMed | University of Maryland Baltimore County, China Medical University at Taichung, Medical University of Graz, George mstock Center For Public Health Research And Prevention and 35 more.
Type: | Journal: American journal of human genetics | Year: 2016

Genome-wide association studies (GWASs) have identified loci for erythrocyte traits in primarily European ancestry populations. We conducted GWAS meta-analyses of six erythrocyte traits in 71,638 individuals from European, East Asian, and African ancestries using a Bayesian approach to account for heterogeneity in allelic effects and variation in the structure of linkage disequilibrium between ethnicities. We identified seven loci for erythrocyte traits including a locus (RBPMS/GTF2E2) associated with mean corpuscular hemoglobin and mean corpuscular volume. Statistical fine-mapping at this locus pointed to RBPMS at this locus and excluded nearby GTF2E2. Using zebrafish morpholino to evaluate loss of function, we observed a strong invivo erythropoietic effect for RBPMS but not for GTF2E2, supporting the statistical fine-mapping at this locus and demonstrating that RBPMS is a regulator of erythropoiesis. Our findings show the utility of trans-ethnic GWASs for discovery and characterization of genetic loci influencing hematologic traits.

Lam T.K.,Johns Hopkins University | Lam T.K.,U.S. National Cancer Institute | Ruczinski I.,Johns Hopkins University | Helzlsouer K.J.,Johns Hopkins University | And 6 more authors.
Cancer Epidemiology Biomarkers and Prevention | Year: 2010

Background: Due predominantly to cigarette smoking, lung cancer is the leading cancer-related cause of death worldwide. Cruciferous vegetables may reduce lung cancer risk. The association between intake of cruciferous vegetables and lung cancer risk was investigated in the CLUE II study, a community-based cohort established in 1989. Methods: We matched 274 incident cases of lung cancer diagnosed from 1990 to 2005 to 1,089 cancer-free controls on age, sex, and cigarette smoking. Dietary information was collected at baseline. Multivariable odds ratios (OR) and 95% confidence intervals (95% CI) were calculated using conditional logistic regression. Results: Intake of cruciferous vegetables was inversely associated with lung cancer risk (highest-versuslowest fourth: ORQ4vsQ1, 0.57; 95% CI, 0.38-0.85; P-trend = 0.01). The inverse associations held true for former smokers (OR Q4vsQ1, 0.49; 95% CI, 0.27-0.92; P-trend = 0.05) and current smokers (ORQ4vsQ1, 0.52; 95% CI, 0.29-0.95; P-trend = 0.02). Conclusions: After carefully controlling for cigarette smoking, higher intake of cruciferous vegetable was associated with lower risk of lung cancer. Impact: The observed inverse association coupled with accumulating evidence suggests that intake of cruciferous vegetables is inversely associated with lung cancer risk, and this association seems to hold true beyond the confounding effects of cigarette smoking. ©2010 AACR.

Kessides M.C.,Johns Hopkins University | Wheless L.,Medical University of South Carolina | Hoffman-Bolton J.,Johns Hopkins University | Hoffman-Bolton J.,George mstock Center For Public Health Research And Prevention | And 5 more authors.
Journal of the American Academy of Dermatology | Year: 2011

Background: Several previous studies have reported inverse associations between cigarette smoking and melanoma. Often these studies have not adjusted for ultraviolet (UV) exposure history, skin type, or number of blistering sunburns, which could confound the observed associations between cigarette smoking and melanoma. Objective: We sought to assess whether this reported inverse association persists after adjusting for UV exposure, skin type, and number of blistering sunburns. Methods: We conducted a population-based case-control study (82 patients with melanoma, 164 control subjects). Two control subjects were matched to each patient by age, sex, race, and skin type. Conditional logistic regression models were fit to assess the association between cigarette smoking history and melanoma, with additional adjustments for UV exposure and sunburns. Results: Compared with never smoking, both former (odds ratio 0.43, 95% confidence interval 0.18-1.04) and current (odds ratio 0.65, 95% confidence interval 0.19-2.24) smoking were inversely associated with melanoma, but the associations were not statistically significant. Limitations: The number of cutaneous nevi was not assessed in this study. In addition, the relatively small number of patients limits the statistical precision of the observed associations. Conclusions: After matching for age, sex, race, and skin type, and further adjusting for UV exposure and number of sunburns, cigarette smoking was not statistically significantly associated with melanoma risk, but the results were consistent with previous observations of an inverse association. © 2009 by the American Academy of Dermatology, Inc.

Coresh J.,Johns Hopkins University | Coresh J.,George mstock Center For Public Health Research And Prevention | Platz E.A.,Johns Hopkins University | Platz E.A.,George mstock Center For Public Health Research And Prevention
American Journal of Epidemiology | Year: 2016

The Johns Hopkins Bloomberg School of Public Health has been engaged in public health research and practice in Washington County, Maryland, nearly since its inception a century ago. In 2005, the center housing this work was renamed the George W. Comstock Center for Public Health Research and Prevention to honor its pioneering leader. Principles that guided innovation and translation well in the past included: research synergies and opportunities for translation realized through longstanding connection with the community; integration of training with public health research; lifelong learning, mentorship, and teamwork; and efficiency through economies of scale. These principles are useful to consider as we face the challenges of improving the health of the population over the next 100 years. © The Author 2016. Published by Oxford University Press on behalf of the Johns Hopkins Bloomberg School of Public Health.

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