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

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. Source

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

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. Source

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.

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. Source

Wheless L.,Medical University of South Carolina | Kistner-Griffin E.,Medical University of South Carolina | Jorgensen T.J.,Georgetown University | Ruczinski I.,Johns Hopkins University | And 12 more authors.
Journal of Investigative Dermatology

Nucleotide excision repair (NER) is responsible for protecting DNA in skin cells against UVR-induced damage. Using a candidate pathway approach, a matched case-control study nested within a prospective, community-based cohort was carried out to test the hypothesis that single-nucleotide polymorphisms (SNPs) in NER genes are associated with susceptibility to non-melanoma skin cancer (NMSC). Histologically confirmed cases of NMSC (n=900) were matched to controls (n=900) on the basis of age, gender, and skin type. Associations were measured between NMSC and 221 SNPs in 26 NER genes. Using the additive model, two tightly linked functional SNPs in ERCC6 were significantly associated with increased risk of NMSC: rs2228527 (odds ratio (OR) 1.57, 95% confidence interval (CI) 1.20-2.05) and rs2228529 (OR 1.57, 95% CI 1.20-2.05). These associations were confined to basal cell carcinoma (BCC) of the skin (rs2228529, OR 1.78, 95% CI 1.30-2.44; rs2228527, OR 1.78, 95% CI 1.31-2.43). These hypothesis-generating findings suggest that functional variants in ERCC6 may be associated with an increased risk of NMSC that may be specific to BCC. © 2012 The Society for Investigative Dermatology. Source

Irani L.,Johns Hopkins University | Lin S.Y.,Johns Hopkins Medical Institutions | Clipp S.L.,Johns Hopkins University | Clipp S.L.,George mstock Center For Public Health Research And Prevention | And 5 more authors.
American Journal of Rhinology and Allergy

Background: Epidemiological evidence evaluating the association between secondhand smoke exposure and diseases of the upper airway in adults is limited by a small number of studies and a lack of established protocols. This study was designed to optimize a research protocol on secondhand tobacco smoke exposure and chronic rhinosinusitis for a future population-based case-control study in Washington County, Maryland, using a participatory research model. Methods: We conducted three focus groups with health professionals, community members, and research practitioners for protocol development; 10 one-on-one cognitive testings with community members for protocol refinement; and a pilot testing of the full study protocol (10 cases and 10 controls) for full evaluation of the study protocol. Results: Health professionals recommended, among other themes, enrolling patients with confirmed chronic rhinosinusitis (minimum 12-week symptom duration and objective inflammation). Community members and research practitioners discussed optimal strategies for participant recruitment and interviewing. The protocol, revised with the focus group's feedback, was further evaluated in one-on-one sessions with 10 Washington County residents (3 with chronic rhinosinusitis). In the pilot study, 10 nonsmoking chronic rhinosinusitis cases (5 clinic based and 5 community based) and their community-based age, sex, and former/never smoking-matched controls were recruited. Sinonasal symptoms scores were higher in cases than controls but similar for clinic versus community-based cases. Conclusion: This protocol development framework involving stakeholders resulted in a comprehensive questionnaire that was successfully evaluated during a pilot study and is now ready to be used in population-based and clinical epidemiological studies of chronic rhinosinusitis in adults. Copyright © 2010, OceanSide Publications, Inc. Source

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