156 results on '"Lisa B. Signorello"'
Search Results
2. A meta-analysis of genome-wide association studies of multiple myeloma among men and women of African ancestry
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Jeffrey A. Zonder, Edward S. Peters, Xin Sheng, Nalini Janakiraman, Frits van Rhee, John D. Carpten, Jennifer J. Hu, Mark A. Fiala, Sagar Lonial, W. Ryan Diver, Wei Zheng, Christopher A. Haiman, Antoinette M. Stroup, Leon Bernal-Mizrachi, William J. Blot, Barbara Nemesure, Loic Le Marchand, Graham A. Colditz, David Van Den Berg, Robert Z. Orlowski, Lisa B. Signorello, Phyllis J. Goodman, Benjamin A. Rybicki, Laurence N. Kolonel, Elad Ziv, Rick A. Kittles, Victor Hom, Howard R. Terebelo, Ajay K. Nooka, Seema Singhal, Thomas G. Martin, Cathryn H. Bock, Brian C.-H. Chiu, Sue A. Ingles, Sarah J. Nyante, Carol Ann Huff, Ann Mohrbacher, Eric A. Klein, Maurizio Zangari, Kristin A. Rand, Michael F. Press, Zhaohui Du, Karen Pawlish, Niels Weinhold, Michael H. Tomasson, Owen W. Stephens, Janet L. Stanford, Ravi Vij, Daniel Auclair, Jayesh Mehta, Daniel O. Stram, Anselm Hennis, Alexander Stram, Gareth J. Morgan, David V. Conti, Jeffrey L. Wolf, Andrew F. Olshan, Esther M. John, Leslie Bernstein, Sonja I. Berndt, Stephen J. Chanock, Gregory Song, Amie E. Hwang, Wendy Cozen, Sikander Ailawadhi, Kenneth C. Anderson, Victoria L. Stevens, Graham Casey, Regina G. Ziegler, and John S. Witte
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Male ,0301 basic medicine ,Oncology ,medicine.medical_specialty ,Clinical Trials and Observations ,Genetic admixture ,Single-nucleotide polymorphism ,Genome-wide association study ,Biology ,Polymorphism, Single Nucleotide ,03 medical and health sciences ,Rare Diseases ,0302 clinical medicine ,Clinical Research ,Internal medicine ,Genetic variation ,Genetics ,medicine ,Humans ,2.1 Biological and endogenous factors ,Genetic Predisposition to Disease ,Polymorphism ,Aetiology ,Allele ,Cancer ,Genetic association ,Prevention ,Human Genome ,Single Nucleotide ,Hematology ,Confidence interval ,030104 developmental biology ,Genetic Loci ,030220 oncology & carcinogenesis ,Meta-analysis ,Female ,Transcriptional Elongation Factors ,Multiple Myeloma ,Genome-Wide Association Study - Abstract
Persons of African ancestry (AA) have a twofold higher risk for multiple myeloma (MM) compared with persons of European ancestry (EA). Genome-wide association studies (GWASs) support a genetic contribution to MM etiology in individuals of EA. Little is known about genetic risk factors for MM in individuals of AA. We performed a meta-analysis of 2 GWASs of MM in 1813 cases and 8871 controls and conducted an admixture mapping scan to identify risk alleles. We fine-mapped the 23 known susceptibility loci to find markers that could better capture MM risk in individuals of AA and constructed a polygenic risk score (PRS) to assess the aggregated effect of known MM risk alleles. In GWAS meta-analysis, we identified 2 suggestive novel loci located at 9p24.3 and 9p13.1 at P < 1 × 10−6; however, no genome-wide significant association was noted. In admixture mapping, we observed a genome-wide significant inverse association between local AA at 2p24.1-23.1 and MM risk in AA individuals. Of the 23 known EA risk variants, 20 showed directional consistency, and 9 replicated at P < .05 in AA individuals. In 8 regions, we identified markers that better capture MM risk in persons with AA. AA individuals with a PRS in the top 10% had a 1.82-fold (95% confidence interval, 1.56-2.11) increased MM risk compared with those with average risk (25%-75%). The strongest functional association was between the risk allele for variant rs56219066 at 5q15 and lower ELL2 expression (P = 5.1 × 10−12). Our study shows that common genetic variation contributes to MM risk in individuals with AA.
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- 2020
3. Methodological Considerations in Estimation of Phenotype Heritability Using Genome-Wide SNP Data, Illustrated by an Analysis of the Heritability of Height in a Large Sample of African Ancestry Adults.
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Fang Chen, Jing He, Jianqi Zhang, Gary K Chen, Venetta Thomas, Christine B Ambrosone, Elisa V Bandera, Sonja I Berndt, Leslie Bernstein, William J Blot, Qiuyin Cai, John Carpten, Graham Casey, Stephen J Chanock, Iona Cheng, Lisa Chu, Sandra L Deming, W Ryan Driver, Phyllis Goodman, Richard B Hayes, Anselm J M Hennis, Ann W Hsing, Jennifer J Hu, Sue A Ingles, Esther M John, Rick A Kittles, Suzanne Kolb, M Cristina Leske, Robert C Millikan, Kristine R Monroe, Adam Murphy, Barbara Nemesure, Christine Neslund-Dudas, Sarah Nyante, Elaine A Ostrander, Michael F Press, Jorge L Rodriguez-Gil, Ben A Rybicki, Fredrick Schumacher, Janet L Stanford, Lisa B Signorello, Sara S Strom, Victoria Stevens, David Van Den Berg, Zhaoming Wang, John S Witte, Suh-Yuh Wu, Yuko Yamamura, Wei Zheng, Regina G Ziegler, Alexander H Stram, Laurence N Kolonel, Loïc Le Marchand, Brian E Henderson, Christopher A Haiman, and Daniel O Stram
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Medicine ,Science - Abstract
Height has an extremely polygenic pattern of inheritance. Genome-wide association studies (GWAS) have revealed hundreds of common variants that are associated with human height at genome-wide levels of significance. However, only a small fraction of phenotypic variation can be explained by the aggregate of these common variants. In a large study of African-American men and women (n = 14,419), we genotyped and analyzed 966,578 autosomal SNPs across the entire genome using a linear mixed model variance components approach implemented in the program GCTA (Yang et al Nat Genet 2010), and estimated an additive heritability of 44.7% (se: 3.7%) for this phenotype in a sample of evidently unrelated individuals. While this estimated value is similar to that given by Yang et al in their analyses, we remain concerned about two related issues: (1) whether in the complete absence of hidden relatedness, variance components methods have adequate power to estimate heritability when a very large number of SNPs are used in the analysis; and (2) whether estimation of heritability may be biased, in real studies, by low levels of residual hidden relatedness. We addressed the first question in a semi-analytic fashion by directly simulating the distribution of the score statistic for a test of zero heritability with and without low levels of relatedness. The second question was addressed by a very careful comparison of the behavior of estimated heritability for both observed (self-reported) height and simulated phenotypes compared to imputation R2 as a function of the number of SNPs used in the analysis. These simulations help to address the important question about whether today's GWAS SNPs will remain useful for imputing causal variants that are discovered using very large sample sizes in future studies of height, or whether the causal variants themselves will need to be genotyped de novo in order to build a prediction model that ultimately captures a large fraction of the variability of height, and by implication other complex phenotypes. Our overall conclusions are that when study sizes are quite large (5,000 or so) the additive heritability estimate for height is not apparently biased upwards using the linear mixed model; however there is evidence in our simulation that a very large number of causal variants (many thousands) each with very small effect on phenotypic variance will need to be discovered to fill the gap between the heritability explained by known versus unknown causal variants. We conclude that today's GWAS data will remain useful in the future for causal variant prediction, but that finding the causal variants that need to be predicted may be extremely laborious.
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- 2015
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4. Allergies and Asthma in Relation to Cancer Risk
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Meier Hsu, Elizabeth D. Kantor, Mengmeng Du, and Lisa B. Signorello
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Adult ,Male ,0301 basic medicine ,Oncology ,medicine.medical_specialty ,Allergy ,Lung Neoplasms ,Epidemiology ,Article ,03 medical and health sciences ,Prostate cancer ,0302 clinical medicine ,Breast cancer ,Risk Factors ,Internal medicine ,Ethnicity ,Hypersensitivity ,medicine ,Humans ,Prospective Studies ,Lung cancer ,Prospective cohort study ,Aged ,Asthma ,business.industry ,Hazard ratio ,Cancer ,Middle Aged ,Prognosis ,medicine.disease ,Southeastern United States ,030104 developmental biology ,030220 oncology & carcinogenesis ,Female ,business ,Follow-Up Studies - Abstract
Background: Allergies and asthma, conditions commonly characterized by immunoglobulin E–mediated atopic reactions, may decrease cancer risk via increases in immunosurveillance, but may increase risk due to persistent immune stimulation. Associations between allergies and asthma and cancer risk remain unclear, and it is unknown whether associations vary by race/ethnicity. Methods: We evaluated these associations in the Southern Community Cohort Study. At baseline (2002–2009), 64,170 participants were queried on history of allergies and asthma; participants were followed through 2011, during which time 3,628 incident, invasive cancers were identified, including 667 lung cancers, 539 breast cancers, and 529 prostate cancers. Cox proportional hazards regression was used to estimate multivariable-adjusted HRs and 95% confidence intervals (CI). Results: Neither allergies nor asthma was associated with risk of developing invasive cancer overall. Asthma was associated with increased lung cancer risk (HR, 1.25; 95% CI, 1.00–1.57), with no variation by race/ethnicity (Pinteraction = 0.84). Conversely, history of allergies was associated with decreased lung cancer risk (HR, 0.80; 95% CI, 0.65–1.00), with an inverse association observed among non-Hispanic whites (HR, 0.65; 95% CI, 0.45–0.94) but not non-Hispanic blacks (HR, 0.95; 95% CI, 0.73–1.25; Pinteraction = 0.10). No statistically significant associations were observed for risk of breast or prostate cancers, overall or by race/ethnicity. Conclusions: No associations were observed for risk of overall cancer, breast cancer, or prostate cancer. While asthma was associated with increased lung cancer risk, history of allergies was associated with decreased risk, an association driven by an inverse association among non-Hispanic whites. Impact: Associations pertaining to lung cancer merit follow up in a large, diverse study.
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- 2019
5. Baseline Prostate-specific Antigen Level in Midlife and Aggressive Prostate Cancer in Black Men
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Lisa B. Signorello, Quoc-Dien Trinh, Adam S. Kibel, Andrew J. Vickers, Mark A. Preston, Kathryn M. Wilson, Lorelei A. Mucci, Hans Lilja, William Blot, Travis Gerke, Mark Steinwandel, Daniel Sjöberg, Sarah C. Markt, and Sigrid Carlsson
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Adult ,Male ,medicine.medical_specialty ,Percentile ,Time Factors ,Urology ,030232 urology & nephrology ,urologic and male genital diseases ,Risk Assessment ,Article ,03 medical and health sciences ,Prostate cancer ,0302 clinical medicine ,Predictive Value of Tests ,Risk Factors ,Internal medicine ,medicine ,Mass Screening ,Humans ,Prospective Studies ,Stage (cooking) ,Prospective cohort study ,Early Detection of Cancer ,Neoplasm Staging ,business.industry ,Incidence ,Age Factors ,Prostatic Neoplasms ,Odds ratio ,Middle Aged ,Prostate-Specific Antigen ,medicine.disease ,Southeastern United States ,Confidence interval ,Black or African American ,Prostate-specific antigen ,Case-Control Studies ,030220 oncology & carcinogenesis ,Kallikreins ,Neoplasm Grading ,business ,Cohort study - Abstract
Background Prostate-specific antigen (PSA) measurement in midlife predicts long-term prostate cancer (PCa) mortality among white men. Objective To determine whether baseline PSA level during midlife predicts risk of aggressive PCa in black men. Design, setting, and participants Nested case-control study among black men in the Southern Community Cohort Study recruited between 2002 and 2009. A prospective cohort in the southeastern USA with recruitment from community health centers. A total of 197 incident PCa patients aged 40–64 yr at study entry and 569 controls matched on age, date of blood draw, and site of enrollment. Total PSA was measured in blood collected and stored at enrollment. Outcome measurements and statistical analysis Total and aggressive PCa (91 aggressive: Gleason ≥7, American Joint Committee on Cancer stage III/IV, or PCa-specific death). Exact conditional logistic regression estimated odds ratios (ORs) with 95% confidence intervals (CIs) for PCa by category of baseline PSA. Results and limitations Median PSA among controls was 0.72, 0.80, 0.94, and 1.03 ng/ml for age groups 40–49, 50–54, 55–59, and 60–64 yr, respectively; 90th percentile levels were 1.68, 1.85, 2.73, and 3.33 ng/ml. Furthermore, 95% of total and 97% of aggressive cases had baseline PSA above the age-specific median. Median follow-up was 9 yr. The OR for total PCa comparing PSA >90th percentile versus ≤median was 83.6 (95% CI, 21.2–539) for 40–54 yr and 71.7 (95% CI, 23.3–288) for 55–64 yr. For aggressive cancer, ORs were 174 (95% CI, 32.3–infinity) for 40–54 yr and 51.8 (95% CI, 11.0–519) for 55–64 yr. A composite endpoint of aggressive PCa based on stage, grade, and mortality was used and is a limitation. Conclusions PSA levels in midlife strongly predicted total and aggressive PCa among black men. PSA levels among controls were similar to those among white controls in prior studies. Patient summary Prostate-specific antigen (PSA) level during midlife strongly predicted future development of aggressive prostate cancer among black men. Targeted screening based on a midlife PSA might identify men at high risk while minimizing screening in those men at low risk.
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- 2019
6. The oral microbiome in relation to pancreatic cancer risk in African Americans
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Yaohua Yang, Hanna Gerlovin, Dominique S. Michaud, Qiuyin Cai, Edward A. Ruiz-Narváez, Jirong Long, Curtis Huttenhower, Julie R. Palmer, Jeremy E. Wilkinson, Brian M. Wolpin, Lisa B. Signorello, Jessica L. Petrick, Xiao-Ou Shu, and W. Evan Johnson
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Male ,Cancer Research ,medicine.medical_specialty ,Population ,Black People ,Article ,Risk Factors ,Internal medicine ,Pancreatic cancer ,medicine ,Tannerella forsythia ,Humans ,Prospective Studies ,education ,education.field_of_study ,Mouth ,biology ,business.industry ,Incidence (epidemiology) ,Microbiota ,Prevotella intermedia ,Odds ratio ,Middle Aged ,biology.organism_classification ,medicine.disease ,Confidence interval ,United States ,Pancreatic Neoplasms ,stomatognathic diseases ,Oncology ,Case-Control Studies ,Female ,Oral Microbiome ,business - Abstract
Background African Americans have the highest pancreatic cancer incidence of any racial/ethnic group in the United States. The oral microbiome was associated with pancreatic cancer risk in a recent study, but no such studies have been conducted in African Americans. Poor oral health, which can be a cause or effect of microbial populations, was associated with an increased risk of pancreatic cancer in a single study of African Americans. Methods We prospectively investigated the oral microbiome in relation to pancreatic cancer risk among 122 African-American pancreatic cancer cases and 354 controls. DNA was extracted from oral wash samples for metagenomic shotgun sequencing. Alpha and beta diversity of the microbial profiles were calculated. Multivariable conditional logistic regression was used to estimate odds ratios (ORs) and 95% confidence intervals (CIs) for associations between microbes and pancreatic cancer risk. Results No associations were observed with alpha or beta diversity, and no individual microbial taxa were differentially abundant between cases and control, after accounting for multiple comparisons. Among never smokers, there were elevated ORs for known oral pathogens: Porphyromonas gingivalis (OR = 1.69, 95% CI: 0.80-3.56), Prevotella intermedia (OR = 1.40, 95% CI: 0.69-2.85), and Tannerella forsythia (OR = 1.36, 95% CI: 0.66-2.77). Conclusions Previously reported associations between oral taxa and pancreatic cancer were not present in this African-American population overall.
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- 2020
7. Novel colon cancer susceptibility variants identified from a genome‐wide association study in African Americans
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Lynne R. Wilkens, Jane C. Figueiredo, Fredrick R. Schumacher, Mala Pande, Christopher A. Haiman, Krista A. Zanetti, Robert W. Haile, Ikuko Kato, Lisa B. Signorello, Sonja I. Berndt, David V. Conti, Temitope O. Keku, Terrilea Burnett, Polly A. Newcomb, Hansong Wang, Daniel O. Stram, Stephanie L. Schmit, Dee W. West, Loic Le Marchand, Curtis C. Harris, Julie R. Palmer, William J. Blot, and David Van Den Berg
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Adult ,Male ,0301 basic medicine ,Cancer Research ,Genotype ,Colorectal cancer ,Genome-wide association study ,Biology ,Polymorphism, Single Nucleotide ,Article ,03 medical and health sciences ,Asian People ,Gene Frequency ,Risk Factors ,medicine ,Humans ,Genetic Predisposition to Disease ,1000 Genomes Project ,Allele ,Alleles ,Aged ,Genetic association ,Genetics ,Genetic diversity ,Nuclear Proteins ,Hispanic or Latino ,Odds ratio ,Middle Aged ,medicine.disease ,Confidence interval ,Black or African American ,030104 developmental biology ,Oncology ,Colonic Neoplasms ,Female ,Chromosomes, Human, Pair 19 ,Genome-Wide Association Study - Abstract
Genome-wide association studies (GWAS) in ethnic/racial minority populations can help to fine-map previously identified risk regions or discover new risk loci because of the genetic diversity in these populations. We conducted a GWAS of colorectal cancer (CRC) in 6,597 African Americans (1,894 cases and 4,703 controls) (Stage 1) and followed up the most promising markers in a replication set of 2,041 participants of African descent (891 cases and 1,150 controls) (Stage 2). We identified a novel variant, rs56848936 in the gene SYMPK at 19q13.3, associated with colon cancer risk (odds ratio 0.61 for the risk allele G, p = 2.4 × 10-8 ). The frequency of the G allele was 0.06 in African Americans, compared to
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- 2017
8. Built Environment and Depression in Low-Income African Americans and Whites
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Jaime E. Hart, Peter James, Francine Laden, Rachel F. Banay, and Lisa B. Signorello
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Adult ,Male ,Gerontology ,Urban Population ,Epidemiology ,Walking ,Article ,White People ,Odds ,Cohort Studies ,03 medical and health sciences ,0302 clinical medicine ,Residence Characteristics ,Humans ,Medicine ,030212 general & internal medicine ,Cities ,Depression (differential diagnoses) ,Built environment ,Social stress ,030505 public health ,Depression ,business.industry ,Public Health, Environmental and Occupational Health ,Middle Aged ,Center for Epidemiologic Studies Depression Scale ,Mental health ,Southeastern United States ,Black or African American ,Walkability ,Female ,0305 other medical science ,business ,Demography ,Cohort study - Abstract
Introduction Urban environments are associated with a higher risk of adverse mental health outcomes; however, it is unclear which specific components of the urban environment drive these associations. Methods Using data collected in 2002–2009 from 73,225 low-income, racially diverse individuals across the Southeastern U.S., analyses evaluated the cross-sectional relationship between a walkability index and depression. Walkability was calculated from population density, street connectivity, and destination count in the 1,200-meter area around participants' homes, and depression was measured using the Center for Epidemiologic Studies Depression Scale for depression symptomatology and questionnaire responses regarding doctor-diagnosed depression and antidepressant use. Data were analyzed in 2015. Results Participants living in neighborhoods with the highest walkability index had 6% higher odds of moderate or greater depression symptoms (score ≥15, 95% CI=0.99, 1.14), 28% higher odds of doctor-diagnosed depression (95% CI=1.20, 1.36), and 16% higher odds of current antidepressant use (95% CI=1.08, 1.25), compared with those in the lowest walkability index. Higher walkability was associated with higher odds of depression symptoms in the most deprived neighborhoods only, whereas walkability was associated with lower odds of depression symptoms in the least deprived neighborhoods. Conclusions Living in a more walkable neighborhood was associated with modestly higher levels of doctor-diagnosed depression and antidepressant use, and walkability was associated with greater depression symptoms in neighborhoods with higher deprivation. Although dense urban environments may provide opportunities for physical activity, they may also increase exposure to noise, air pollution, and social stressors that could increase levels of depression.
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- 2017
9. Association of Blood Marker of Inflammation in Late Adolescence With Premature Mortality
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Edward Giovannucci, Elizabeth D. Kantor, Unnur Valdimarsdóttir, Scott Montgomery, Lisa B. Signorello, Katja Fall, and Ruzan Udumyan
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medicine.medical_specialty ,medicine.diagnostic_test ,business.industry ,Blood marker ,Inflammation ,Late adolescence ,Premature death ,Erythrocyte sedimentation rate ,Internal medicine ,Pediatrics, Perinatology and Child Health ,medicine ,Research Letter ,medicine.symptom ,business - Abstract
This study evaluates the association of inflammation in late adolescence as measured by erythrocyte sedimentation rate with cause-specific mortality among healthy Swedish men assessed for conscription in the military.
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- 2019
10. Use of glucosamine and chondroitin supplements in relation to risk of colorectal cancer: Results from the Nurses' Health Study and Health Professionals follow-up study
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Andrew T. Chan, Edward Giovannucci, Charles S. Fuchs, Kana Wu, Lisa B. Signorello, Elizabeth D. Kantor, and Xuehong Zhang
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0301 basic medicine ,Cancer Research ,medicine.medical_specialty ,Proportional hazards model ,business.industry ,03 medical and health sciences ,chemistry.chemical_compound ,030104 developmental biology ,0302 clinical medicine ,Oncology ,chemistry ,Glucosamine ,030220 oncology & carcinogenesis ,Relative risk ,Internal medicine ,Cohort ,medicine ,Chondroitin ,Nurses' Health Study ,Prospective cohort study ,business ,Body mass index - Abstract
Recent epidemiologic evidence has emerged to suggest that use of glucosamine and chondroitin supplements may be associated with reduced risk of colorectal cancer (CRC). We therefore evaluated the association between use of these non-vitamin, non-mineral supplements and risk of CRC in two prospective cohorts, the Nurses' Health Study and Health Professionals Follow-up Study. Regular use of glucosamine and chondroitin was first assessed in 2002 and participants were followed until 2010, over which time 672 CRC cases occurred. Cox proportional hazards regression was used to estimate relative risks (RRs) within each cohort, and results were pooled using a random effects meta-analysis. Associations were comparable across cohorts, with a RR of 0.79 (95% CI: 0.63-1.00) observed for any use of glucosamine and a RR of 0.77 (95% CI: 0.59-1.01) observed for any use of chondroitin. Use of glucosamine in the absence of chondroitin was not associated with risk of CRC, whereas use of glucosamine + chondroitin was significantly associated with risk (RR: 0.77; 95% CI: 0.58-0.999). The association between use of glucosamine + chondroitin and risk of CRC did not change markedly when accounting for change in exposure status over follow-up (RR: 0.75; 95% CI: 0.58-0.96), nor did the association significantly vary by sex, aspirin use, body mass index, or physical activity. The association was comparable for cancers of the colon and rectum. Results support a protective association between use of glucosamine and chondroitin and risk of CRC. Further study is needed to better understand the chemopreventive potential of these supplements.
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- 2016
11. Genome-wide association studies in women of African ancestry identified 3q26.21 as a novel susceptibility locus for oestrogen receptor negative breast cancer
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Sue A. Ingles, Esther M. John, Regina G. Ziegler, Stephen A. Haddad, Yonglan Zheng, Oladosu Ojengbede, Lara E. Sucheston-Campbell, Ye Feng, Laurence N. Kolonel, William J. Blot, Christine B. Ambrosone, Lin Chen, Wei Zheng, Stephen J. Chanock, Jorge L. Rodriguez-Gil, Sandra L. Deming, Qiuyin Cai, Andrew F. Olshan, Anselm Hennis, Nancy J. Cox, Song Yao, Edward A. Ruiz-Narváez, Sarah J. Nyante, Timothy R. Rebbeck, Susan M. Domchek, Michael F. Press, Eric R. Gamazon, Katherine L. Nathanson, Kathryn L. Lunetta, Temidayo O. Ogundiran, Frank Qian, Jennifer J. Hu, Leslie Bernstein, Christopher A. Haiman, Lisa B. Signorello, Barbara Nemesure, Olufunmilayo I. Olopade, Clement Adebamowo, M. Cristina Leske, Elisa V. Bandera, Stefan Ambs, Jeannette T. Bensen, Yoo Jeong Han, Michael S. Simon, Adeyinka G. Falusi, Dezheng Huo, Julie R. Palmer, and Graduate School
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0301 basic medicine ,Oncology ,medicine.medical_specialty ,Estrogen receptor ,Black People ,Genome-wide association study ,Single-nucleotide polymorphism ,Breast Neoplasms ,Biology ,Polymorphism, Single Nucleotide ,TNF-Related Apoptosis-Inducing Ligand ,03 medical and health sciences ,0302 clinical medicine ,Breast cancer ,Gene Frequency ,Risk Factors ,Internal medicine ,Genetics ,medicine ,SNP ,Humans ,Genetic Predisposition to Disease ,Molecular Biology ,Genetics (clinical) ,Alleles ,Genetic association ,Association Studies Articles ,Case-control study ,General Medicine ,Odds ratio ,medicine.disease ,Black or African American ,030104 developmental biology ,Receptors, Estrogen ,Genetic Loci ,030220 oncology & carcinogenesis ,Case-Control Studies ,Female ,Chromosomes, Human, Pair 3 ,Genome-Wide Association Study - Abstract
Multiple breast cancer loci have been identified in previous genome-wide association studies, but they were mainly conducted in populations of European ancestry. Women of African ancestry are more likely to have young-onset and oestrogen receptor (ER) negative breast cancer for reasons that are unknown and understudied. To identify genetic risk factors for breast cancer in women of African descent, we conducted a meta-analysis of two genome-wide association studies of breast cancer; one study consists of 1,657 cases and 2,029 controls genotyped with Illumina's HumanOmni2.5 BeadChip and the other study included 3,016 cases and 2,745 controls genotyped using Illumina Human1M-Duo BeadChip. The top 18,376 single nucleotide polymorphisms (SNP) from the meta-analysis were replicated in the third study that consists of 1,984 African Americans cases and 2,939 controls. We found that SNP rs13074711, 26.5 Kb upstream of TNFSF10 at 3q26.21, was significantly associated with risk of oestrogen receptor (ER)-negative breast cancer (odds ratio [OR]=1.29, 95% CI: 1.18-1.40; P = 1.8 × 10 (-) (8)). Functional annotations suggest that the TNFSF10 gene may be involved in breast cancer aetiology, but further functional experiments are needed. In addition, we confirmed SNP rs10069690 was the best indicator for ER-negative breast cancer at 5p15.33 (OR = 1.30; P = 2.4 × 10 (-) (10)) and identified rs12998806 as the best indicator for ER-positive breast cancer at 2q35 (OR = 1.34; P = 2.2 × 10 (-) (8)) for women of African ancestry. These findings demonstrated additional susceptibility alleles for breast cancer can be revealed in diverse populations and have important public health implications in building race/ethnicity-specific risk prediction model for breast cancer.
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- 2016
12. Socioenvironmental adversity and risk of prostate cancer in non-Hispanic black and white men
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Sebastien Haneuse, Lisa B. Signorello, Unnur Valdimarsdóttir, Elizabeth D. Kantor, Jennifer R. Rider, and David R. Williams
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Adult ,Male ,Cancer Research ,medicine.medical_specialty ,Ethnic group ,Perceived Stress Scale ,Social Environment ,White People ,Article ,Cohort Studies ,03 medical and health sciences ,Prostate cancer ,Social support ,0302 clinical medicine ,Risk Factors ,Epidemiology ,medicine ,Humans ,030212 general & internal medicine ,Socioeconomic status ,Aged ,business.industry ,Public health ,Prostatic Neoplasms ,Middle Aged ,medicine.disease ,Black or African American ,Oncology ,Social Class ,030220 oncology & carcinogenesis ,business ,Demography ,Cohort study - Abstract
Non-Hispanic black (NHB) men experience higher risk of prostate cancer than other racial/ethnic groups, and it is possible that socioenvironmental (SE) adversity and resulting stress may contribute to this disparity. Data from the Southern Community Cohort Study were used to evaluate associations between SE adversity and perceived stress in relation to prostate cancer risk, overall and by race/ethnicity and grade. Between 2002 and 2009, 26,741 men completed a questionnaire, from which an 8-item SE adversity composite was created (covering socioeconomic status, residential environment, and social support/buffers). Two items from the Perceived Stress Scale were assessed. With follow-up through 2011, 527 prostate cancer cases were diagnosed. In multivariable models, each one-unit increase in the SE adversity composite was associated with increased prostate cancer risk among non-Hispanic white (NHW) men (HR 1.23; 95% CI 1.02-1.48) and reduced risk among NHB men (HR 0.89; 95% CI 0.82-0.95) (p interaction: 0.001). This pattern held for low grade, but not high grade, cancers although power was limited for the latter. Perceived stress variables were associated with increased risk of prostate cancer among NHW men, but not among NHB men. Results do not support the hypothesis that SE adversity my underlay the racial disparity in prostate cancer, over and above that of covariates, including healthcare utilization.
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- 2018
13. Persistence of Trichomonas vaginalis serostatus in men over time
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Charlotte A. Gaydos, Lisa B. Signorello, Siobhan Sutcliffe, John F. Alderete, Lorelei A. Mucci, Patrick A. Joyce, James I. A. Huth, and Calvin J. Neace
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Adult ,Male ,Cancer Research ,medicine.medical_specialty ,Time Factors ,Antibodies, Protozoan ,Trichomonas Infections ,Enzyme-Linked Immunosorbent Assay ,medicine.disease_cause ,Article ,Persistence (computer science) ,Cohort Studies ,Prostate cancer ,Sex Factors ,Risk Factors ,Epidemiology ,Trichomonas vaginalis ,medicine ,Humans ,Aged ,biology ,business.industry ,Public health ,Prostatic Neoplasms ,Middle Aged ,medicine.disease ,Oncology ,Immunology ,biology.protein ,Antibody ,Serostatus ,business ,Demography ,Cohort study - Abstract
Previous epidemiologic studies have observed positive associations between Trichomonas vaginalis (Tv) serostatus and both prostate cancer (PCa) risk and mortality. However, only a few small older studies have examined Tv antibody persistence over time, all of which were composed mainly of female patients. Therefore, we examined Tv antibody persistence over time, as well as intra-individual variability, among middle- to older-aged men in the Southern Community Cohort Study (SCCS).We tested baseline and repeat plasma specimens (collected 1-3 years later) from 248 male participants for Tv antibodies. We used the same enzyme-linked immunosorbent assay as in previous studies of Tv serostatus and PCa.At baseline, 46 (18.5 %) participants were seropositive for Tv infection. Seventy-six percent of these men were still seropositive 1-3 years later. A similar proportion of men "seroconverted" (4.0 %) as "seroreverted" (4.4 %), all of whom had absorbance values near the cutoff point for seropositivity. Overall, substantial agreement was observed between baseline and repeat serostatus (κ = 0.72, 95 % confidence interval 0.60-0.83).Tv seropositivity was largely persistent between plasma specimens collected 1-3 years apart from middle- to older-aged men. These high levels of persistence are similar to those observed for other sexually transmitted infections frequently investigated in relation to PCa.
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- 2015
14. Statin use and risk of prostate cancer: Results from the Southern Community Cohort Study
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Edward Giovannucci, Lisa B. Signorello, Lorelei A. Mucci, Loren Lipworth, Jay H. Fowke, and Elizabeth D. Kantor
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Gynecology ,Oncology ,medicine.medical_specialty ,business.industry ,Proportional hazards model ,Urology ,Hazard ratio ,Cancer ,medicine.disease ,Lower risk ,Confidence interval ,Prostate cancer ,medicine.anatomical_structure ,Prostate ,Internal medicine ,Medicine ,business ,Cohort study - 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 4 + 3). Analyses of overall prostate cancer were conducted using Cox regression and analyses of grade-specific cancer were conducted using competing risks models. RESULTS Ten 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 75:1384–1393, 2015. © 2015 Wiley Periodicals, Inc.
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- 2015
15. Adolescent body mass index and erythrocyte sedimentation rate in relation to colorectal cancer risk
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Ruzan Udumyan, Lisa B. Signorello, Elizabeth D. Kantor, Edward Giovannucci, Katja Fall, and Scott Montgomery
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Adult ,Male ,medicine.medical_specialty ,Adolescent ,Colorectal cancer ,Blood Sedimentation ,Overweight ,Article ,Body Mass Index ,Cohort Studies ,03 medical and health sciences ,0302 clinical medicine ,Risk Factors ,Internal medicine ,Outcome Assessment, Health Care ,medicine ,Humans ,Obesity ,030212 general & internal medicine ,Proportional Hazards Models ,Inflammation ,Sweden ,medicine.diagnostic_test ,Proportional hazards model ,business.industry ,Gastroenterology ,medicine.disease ,Cancer registry ,Surgery ,030220 oncology & carcinogenesis ,Erythrocyte sedimentation rate ,Cohort ,medicine.symptom ,Colorectal Neoplasms ,business ,Body mass index - Abstract
Adult obesity and inflammation have been associated with risk of colorectal cancer (CRC); however, less is known about how adolescent body mass index (BMI) and inflammation, as measured by erythrocyte sedimentation rate (ESR), relate to CRC risk. We sought to evaluate these associations in a cohort of 239 658 Swedish men who underwent compulsory military enlistment examinations in late adolescence (ages 16-20 years).At the time of the conscription assessment (1969-1976), height and weight were measured and ESR was assayed. By linkage to the national cancer registry, these conscripts were followed for CRC through 1 January 2010. Over an average of 35 years of follow-up, 885 cases of CRC occurred, including 501 colon cancers and 384 rectal cancers. Cox regression was used to estimate adjusted HRs and corresponding 95% CIs.Compared with normal weight (BMI 18.5 to25 kg/m(2)) in late adolescence, upper overweight (BMI 27.5 to30 kg/m(2)) was associated with a 2.08-fold higher risk of CRC (95% CI 1.40 to 3.07) and obesity (BMI 30+ kg/m(2)) was associated with a 2.38-fold higher risk of CRC (95% CI 1.51 to 3.76) (p-trend:0.001). Male adolescents with ESR (15+ mm/h) had a 63% higher risk of CRC (HR 1.63; 95% CI 1.08 to 2.45) than those with low ESR (10 mm/h) (p-trend: 0.006). Associations did not significantly differ by anatomic site.Late-adolescent BMI and inflammation, as measured by ESR, may be independently associated with future CRC risk. Further research is needed to better understand how early-life exposures relate to CRC.
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- 2015
16. Body Mass Index in Young Adulthood, Obesity Trajectory, and Premature Mortality
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William J. Blot, Meir J. Stampfer, Elizabeth D. Kantor, Sarah S. Cohen, Kelly A. Hirko, and Lisa B. Signorello
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Adult ,Male ,Gerontology ,Alcohol Drinking ,Epidemiology ,Original Contributions ,Overweight ,Body Mass Index ,Cohort Studies ,Risk Factors ,Neoplasms ,Humans ,Medicine ,Obesity ,Young adult ,Aged ,Proportional Hazards Models ,Mortality, Premature ,Proportional hazards model ,business.industry ,Incidence ,Mortality rate ,Smoking ,Hazard ratio ,Middle Aged ,United States ,Confidence interval ,Socioeconomic Factors ,Cardiovascular Diseases ,Female ,medicine.symptom ,business ,Body mass index ,Demography ,Cohort study - Abstract
Although much research has been conducted on the role adult body mass index (BMI) plays in mortality, there have been fewer studies that evaluated the associations of BMI in young adulthood and adult weight trajectory with mortality, and it remains uncertain whether associations differ by race or sex. We prospectively examined the relationships of BMI in young adulthood (21 years of age) and adult obesity trajectory with later-life mortality rates among 75,881 men and women in the Southern Community Cohort Study. Study participants were enrolled between 2002 and 2009 at ages 40–79 years and were followed through December, 2011. Multivariable Cox proportional hazards models were used to estimate hazard ratios and 95% confidence intervals. There were 7,301 deaths in the 474,970 person-years of follow-up. Participants who reported being overweight or obese as young adults had mortality rates that were 19% (95% confidence interval: 12, 27) and 64% (95% confidence interval: 52, 78) higher, respectively, than those of their normal weight counterparts. The results did not significantly differ by race or sex. Participants who reported being obese in young adulthood only or in both young and middle adulthood experienced mortality rates that were 40%–90% higher than those of participants who were nonobese at either time. These results suggest that obesity in young adulthood is associated with higher mortality risk regardless of race, sex, and obesity status in later life.
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- 2015
17. Genome-wide association analysis of more than 120,000 individuals identifies 15 new susceptibility loci for breast cancer
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Vesa Kataja, Aida Karina Dieffenbach, Chia-Ni Hsiung, Catherine S. Healey, Gie Hooi Tan, Soo Hwang Teo, Domenico Palli, Frederik Marme, Katri Pylkäs, Roger L. Milne, Jaana M. Hartikainen, Gord Glendon, Susan L. Slager, Chen-Yang Shen, Fredrick R. Schumacher, Daniel F. Schmidt, Suleeporn Sangrajrang, Kee Seng Chia, Lorna Gibson, Pascal Guénel, Alice S. Whittemore, Jenny Chang-Claude, Yu Tang Gao, Hidemi Ito, Simon S. Cross, Sofia Khan, Marie Sanchez, Daniel Vincent, Daniel Herrero, Nicola Miller, Antoinette Hollestelle, Caroline M. Seynaeve, Christopher A. Haiman, Hermann Brenner, Kay-Tee Khaw, Loris Bernard, Habibul Ahsan, Melissa C. Southey, David Van Den Berg, Martha J. Shrubsole, Daniel O. Stram, William Blot, Mel Maranian, Robert Winqvist, Keitaro Matsuo, John W. M. Martens, Heli Nevanlinna, Mia M. Gaudet, Anna Jakubowska, Christine D. Berg, Paul D.P. Pharoah, Jacques Simard, Manjeet K. Bolla, Dieter Flesch-Janys, Mark S. Goldberg, Paul Brennan, Ching Wan Chan, Sune F. Nielsen, Sara Lindström, Mitul Shah, Matthias W. Beckmann, Craig Luccarini, Jonathan Beesley, Kyriaki Michailidou, Paolo Peterlongo, Marc J. Gunter, Anna González-Neira, Ji Yeob Choi, Per Hall, Sarah Stewart-Brown, Keith Humphreys, Hui Cai, Kathleen E. Malone, Elinor J. Sawyer, Louise A. Brinton, Marjanka K. Schmidt, Xiao-Ou Shu, Barbara Perkins, Lotte Maxild Mortensen, Chiu-Chen Tseng, Hanne Meijers-Heijboer, Minouk J. Schoemaker, Keun-Young Yoo, Julia A. Knight, Alan Ashworth, Stig E. Bojesen, Kamila Czene, Artitaya Lophatananon, Graham G. Giles, S. Ahmed, Kazuo Tajima, Douglas F. Easton, Maria Kabisch, Arja Jukkola-Vuorinen, Wei Lu, Peter A. Fasching, Irene L. Andrulis, Clare Turnbull, Caroline Baynes, Christine B. Ambrosone, Jan Lubinski, Muriel A. Adank, A. Meindl, Taru A. Muranen, Siranoush Manoukian, Susan M. Gapstur, Natalia Bogdanova, Alexander Hein, Annika Lindblom, Nazneen Rahman, Annegien Broeks, Lothar Haeberle, Federico Canzian, G Pita, Ming-Feng Hou, Hiroji Iwata, Drakoulis Yannoukakos, Diana Torres, Vessela N. Kristensen, Peter Devilee, Qiuyin Cai, Christi J Asperen, John L. Hopper, Diether Lambrechts, Michael Lush, Hans Wildiers, Joe Dennis, Sandra L. Halverson, Carl Blomqvist, Erik Van Limbergen, Malin Sund, Daehee Kang, Grethe I. Grenaker Alnæs, Marilie D. Gammon, Ursula Eilber, Ian Tomlinson, Thérèse Truong, Amanda E. Toland, Anna Marie Mulligan, Kirsimari Aaltonen, Olivia Fletcher, Jonine D. Figueroa, Angela Cox, Pei Ei Wu, Maartje J. Hooning, Catriona McLean, Georgia Chenevix-Trench, Pornthep Siriwanarangsan, Malcolm W.R. Reed, Emily Hallberg, Sara Margolin, Volker Arndt, Montserrat Garcia-Closas, Francois Bacot, Rita K. Schmutzler, Julian Peto, David J. Hunter, Thomas Brüning, Katarzyna Jaworska, Christof Sohn, Børge G. Nordestgaard, Enes Makalic, Hatef Darabi, Barbara Burwinkel, Petra P.H. Peeters, J. Margriet Collée, Rongxi Yang, Robert N. Hoover, Eiliv Lund, Fergus J. Couch, Ute Hamann, Jirong Long, Wei Zheng, Sabine Behrens, Giske Ursin, Muhammad G. Kibriya, Claire Mulot, Laure Dossus, Helen Tsimiklis, Tomasz Huzarski, Peter Kraft, Anja Rudolph, Arto Mannermaa, Alison M. Dunning, Lisa B. Signorello, Valerie Gaborieau, Kenneth Muir, Anthony J. Swerdlow, Javier Benitez, Judith S. Brand, Sander Canisius, Hoda Anton-Culver, Veli-Matti Kosma, Thilo Dörk, Sten Cornelissen, Christa Stegmaier, Cheng Har Yip, Brian E. Henderson, Harald Surowy, Jingmei Li, Nur Aishah Taib, W. Ryan Diver, Carmel Apicella, Janet E. Olson, Kristiina Aittomäki, Celine M. Vachon, Regina M. Santella, Dimitrios Trichopoulos, Jianjun Liu, Nick Orr, Martine Dumont, Christian Sutter, Sue K. Park, Mikael Hartman, Susan L. Neuhausen, Hui Miao, M. Pilar Zamora, Anna H. Wu, Rob B. van der Luijt, Isabel dos-Santos-Silva, Graham Casey, Henrik Flyger, M. Rosario Alonso, Nuria Álvarez, Michael J. Kerin, Loic Le Marchand, Jose Ignacio Arias Perez, Mikael Eriksson, Esther M. John, Quinten Waisfisz, Qin Wang, Daniel C. Tessier, Paolo Radice, Robert A.E.M. Tollenaar, James McKay, Silje Nord, Hiltrud Brauch, José María Huerta, Stephen J. Chanock, Mervi Grip, Patrick Neven, Senno Verhoef, Clinical Genetics, Obstetrics & Gynecology, Medical Oncology, Cardiothoracic Surgery, Dennis, Joe [0000-0003-4591-1214], Wang, Jean [0000-0002-9139-0627], Khaw, Kay-Tee [0000-0002-8802-2903], Pharoah, Paul [0000-0001-8494-732X], Dunning, Alison [0000-0001-6651-7166], Easton, Douglas [0000-0003-2444-3247], Apollo - University of Cambridge Repository, Human genetics, and CCA - Oncogenesis
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Breast Neoplasms ,Single-nucleotide polymorphism ,Genome-wide association study ,Biology ,Research Support ,Polymorphism, Single Nucleotide ,N.I.H ,Cohort Studies ,brca1 ,Breast cancer ,Research Support, N.I.H., Extramural ,Meta-Analysis as Topic ,SDG 3 - Good Health and Well-being ,common variants ,Journal Article ,estrogen ,chek2-asterisk-1100delc ,Genetics ,medicine ,Humans ,Genetic Predisposition to Disease ,1000 Genomes Project ,Non-U.S. Gov't ,genotype imputation ,risk ,Genetic association ,Research Support, Non-U.S. Gov't ,Chromatin binding ,Extramural ,Cancer ,Microarray Analysis ,confer susceptibility ,medicine.disease ,3. Good health ,ovarian-cancer ,Genetic Loci ,Case-Control Studies ,alleles ,Female ,Imputation (genetics) ,Genome-Wide Association Study ,metaanalysis - Abstract
Genome-wide association studies (GWAS) and large-scale replication studies have identified common variants in 79 loci associated with breast cancer, explaining ∼14% of the familial risk of the disease. To identify new susceptibility loci, we performed a meta-analysis of 11 GWAS, comprising 15,748 breast cancer cases and 18,084 controls together with 46,785 cases and 42,892 controls from 41 studies genotyped on a 211,155-marker custom array (iCOGS). Analyses were restricted to women of European ancestry. We generated genotypes for more than 11 million SNPs by imputation using the 1000 Genomes Project reference panel, and we identified 15 new loci associated with breast cancer at P < 5 × 10(-8). Combining association analysis with ChIP-seq chromatin binding data in mammary cell lines and ChIA-PET chromatin interaction data from ENCODE, we identified likely target genes in two regions: SETBP1 at 18q12.3 and RNF115 and PDZK1 at 1q21.1. One association appears to be driven by an amino acid substitution encoded in EXO1. ispartof: Nature Genetics vol:47 issue:4 pages:373-80 ispartof: location:United States status: published
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- 2015
18. Socioeconomic Status, Race, and Mortality: A Prospective Cohort Study
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William J. Blot, Margaret K. Hargreaves, Lisa B. Signorello, Sarah S. Cohen, Heather M. Munro, and David R. Williams
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Adult ,Male ,Social class ,White People ,Online Research and Practice ,Risk Factors ,Humans ,Medicine ,Prospective Studies ,Mortality ,Prospective cohort study ,Socioeconomic status ,Aged ,Demography ,Proportional hazards model ,business.industry ,Hazard ratio ,Public Health, Environmental and Occupational Health ,social sciences ,Middle Aged ,United States ,Confidence interval ,Black or African American ,Social Class ,Cohort ,population characteristics ,Female ,business ,Cohort study - Abstract
Objectives. We evaluated the independent and joint effects of race, individual socioeconomic status (SES), and neighborhood SES on mortality risk. Methods. We conducted a prospective analysis involving 52 965 non-Hispanic Black and 23 592 non-Hispanic White adults taking part in the Southern Community Cohort Study. Cox proportional hazards modeling was used to determine associations of race and SES with all-cause and cause-specific mortality. Results. In our cohort, wherein Blacks and Whites had similar individual SES, Blacks were less likely than Whites to die during the follow-up period (hazard ratio [HR] = 0.78; 95% confidence interval [CI] = 0.73, 0.84). Low household income was a strong predictor of all-cause mortality among both Blacks and Whites (HR = 1.76; 95% CI = 1.45, 2.12). Being in the lowest (vs highest) category with respect to both individual and neighborhood SES was associated with a nearly 3-fold increase in all-cause mortality risk (HR = 2.76; 95% CI = 1.99, 3.84). There was no significant mortality-related interaction between individual SES and neighborhood SES among either Blacks or Whites. Conclusions. SES is a strong predictor of premature mortality, and the independent associations of individual SES and neighborhood SES with mortality risk are similar for Blacks and Whites.
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- 2014
19. Generalizability of established prostate cancer risk variants in men of African ancestry
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Rosalind A. Eeles, Benjamin A. Rybicki, John S. Witte, W. Ryan Diver, Esther M. John, Lisa Chu, Sue A. Ingles, Eric A. Klein, Timothy R. Rebbeck, William J. Blot, John D. Carpten, Jong Y. Park, William B. Isaacs, Ying Han, Phyllis J. Goodman, Suh Yuh Wu, Janet L. Stanford, Brian E. Henderson, Sonja I. Berndt, S. Lilly Zheng, Christopher A. Haiman, Kristin A. Rand, Barbara Nemesure, Loic Le Marchand, Curtis A. Pettaway, Stephen J. Chanock, Ann W. Hsing, Graham Casey, Lisa B. Signorello, Susan M. Gapstur, Christine Neslund-Dudas, Suzanne Kolb, Adam B. Murphy, Rick A. Kittles, Douglas F. Easton, Jianfeng Xu, Sara S. Strom, M. Cristina Leske, Fredrick R. Schumacher, David V. Conti, Adam S. Kibel, Daniel O. Stram, and Anselm Hennis
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Genetics ,Oncology ,Cancer Research ,medicine.medical_specialty ,Case-control study ,Genome-wide association study ,Odds ratio ,Biology ,medicine.disease ,Logistic regression ,Prostate cancer ,Internal medicine ,medicine ,Allele ,Genetic association ,Cohort study - Abstract
Genome-wide association studies have identified more than 80 risk variants for prostate cancer, mainly in European or Asian populations. The generalizability of these variants in other racial/ethnic populations needs to be understood before the loci can be used widely in risk modeling. In our study, we examined 82 previously reported risk variants in 4,853 prostate cancer cases and 4,678 controls of African ancestry. We performed association testing for each variant using logistic regression adjusted for age, study and global ancestry. Of the 82 known risk variants, 68 (83%) had effects that were directionally consistent in their association with prostate cancer risk and 30 (37%) were significantly associated with risk at p < 0.05, with the most statistically significant variants being rs116041037 (p = 3.7 × 10(-26) ) and rs6983561 (p = 1.1 × 10(-16) ) at 8q24, as well as rs7210100 (p = 5.4 × 10(-8) ) at 17q21. By exploring each locus in search of better markers, the number of variants that captured risk in men of African ancestry (p < 0.05) increased from 30 (37%) to 44 (54%). An aggregate score comprised of these 44 markers was strongly associated with prostate cancer risk [per-allele odds ratio (OR) = 1.12, p = 7.3 × 10(-98) ]. In summary, the consistent directions of effects for the vast majority of variants in men of African ancestry indicate common functional alleles that are shared across populations. Further exploration of these susceptibility loci is needed to identify the underlying biologically relevant variants to improve prostate cancer risk modeling in populations of African ancestry.
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- 2014
20. A meta-analysis of 87,040 individuals identifies 23 new susceptibility loci for prostate cancer
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Laurie Burdette, Rick A. Kittles, Hidewaki Nakagawa, Janet L. Stanford, Wojciech Kluźniak, Karen Park, Sofia Maia, Lisa A. Cannon-Albright, Douglas F. Easton, Dennis J. Hazelett, Hermann Brenner, Paula Paulo, Peter Klarskov, Zhaoming Wang, Koveela Govindasami, Loic Le Marchand, David V. Conti, Phyllis J. Goodman, Chavdar Slavov, Manuel R. Teixeira, Sara Lindström, Maren Weischer, Suzanne Kolb, Lisa B. Signorello, Jianfeng Xu, W. Ryan Diver, Barbara Nemesure, Fredrick R. Schumacher, Michael B. Cook, Qiyuan Li, William J. Blot, Jyotsna Batra, Malgorzata Tymrakiewicz, Anand P. Chokkalingam, Esther M. John, Christopher A. Haiman, Merideth Yeager, David E. Neal, John D. Carpten, Daniel Leongamornlert, Cezary Cybulski, Kathryn L. Penney, Sara Benlloch, Peter Iversen, Judith A. Clements, Shannon K. McDonnell, Matthew L. Freedman, Adam B. Murphy, Mahbubl Ahmed, Kenneth Muir, Sonja I. Berndt, Aida Karina Dieffenbach, Cristina Leske, William B. Isaacs, Chee Goh, Edward D. Yeboah, Jong Y. Park, Ruth C. Travis, Atsushi Takahashi, Nora Pashayan, Timothy J. Key, Evelyn Tay, Lorelei A. Mucci, Edward Giovannucci, Stephen N. Thibodeau, Fredrik Wiklund, Amanda B. Spurdle, Teuvo L.J. Tammela, Peter Kraft, Johanna Schleutker, Melissa C. Southey, Elio Riboli, Afshan Siddiq, Sara S. Strom, Hardev Pandha, Curtis A. Pettaway, Sue A. Ingles, Demetrius Albanes, Brian E. Henderson, Rosalind A. Eeles, Meir J. Stampfer, Markus Aly, Suh-Yuh Wu, Constance Chen, Sune F. Nielsen, Federico Canzian, Christa Stegmaier, Hui-Yi Lin, Amy K. Hutchinson, John S. Witte, Andrzej M. Kierzek, Elizabeth M. Gillanders, Vanio Mitev, Dominika Wokołorczyk, Ali Amin Al Olama, Richard B. Biritwum, Andrew A. Adjei, Ann Truelove, Daniel J. Schaid, Mitchell J. Machiela, Graham Casey, Børge G. Nordestgaard, Wei Zheng, Tokhir Dadaev, Thomas A. Sellers, Lucy Xia, Antonio Hurtado Coll, Tiina Wahlfors, Paul D.P. Pharoah, Jenny L Donovan, Victoria L. Stevens, Kristin A. Rand, Kai Yu, Alex Stram, Anssi Auvinen, Lisa Chu, Adam S. Kibel, Yao Tettey, Gerhard A. Coetzee, Martin Andreas Røder, Gianluca Severi, Daniel O. Stram, Anselm Hennis, Charles C. Chung, Jing Ma, Stephen J. Chanock, Katri A. Leinonen, Stephanie J. Weinstein, Jonathan Tyrer, Freddie C. Hamdy, Shelley Niwa, Kathleen Herkommer, Beatrice S. Knudsen, Laurence N. Kolonel, David J. Hunter, Christine Neslund-Dudas, Loreall Pooler, Robert N. Hoover, Antje E. Rinckleb, Jarmo Virtamo, Henrik Grönberg, Peggy Wan, Eric A. Klein, Michelle Guy, Manuel Luedeke, Radka Kaneva, Xin Sheng, Zsofia Kote-Jarai, Daniella Seminara, Tapio Visakorpi, Christiane Maier, Ann W. Hsing, Susan M. Gapstur, Sara Jugurnauth-Little, Ying Han, Ed Saunders, Agnieszka Michael, Alan W. Partin, Graham G. Giles, S. Lilly Zheng, Michiaki Kubo, Benjamin A. Rybicki, Kay-Tee Khaw, and Sarah K. Holt
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Male ,Genotype ,Single-nucleotide polymorphism ,Genome-wide association study ,Disease ,Biology ,ta3111 ,Polymorphism, Single Nucleotide ,Risk Assessment ,Article ,Prostate cancer ,Risk Factors ,Genetics ,medicine ,Humans ,Genetic Predisposition to Disease ,Genetic association ,ta113 ,ta112 ,ta1184 ,ta1182 ,Cancer ,Prostatic Neoplasms ,medicine.disease ,ta3122 ,Genetic Loci ,Meta-analysis ,Genome-Wide Association Study - Abstract
Genome-wide association studies (GWAS) have identified 76 variants associated with prostate cancer risk predominantly in populations of European ancestry. To identify additional susceptibility loci for this common cancer, we conducted a meta-analysis of > 10 million SNPs in 43,303 prostate cancer cases and 43,737 controls from studies in populations of European, African, Japanese and Latino ancestry. Twenty-three new susceptibility loci were identified at association P < 5 × 10(-8); 15 variants were identified among men of European ancestry, 7 were identified in multi-ancestry analyses and 1 was associated with early-onset prostate cancer. These 23 variants, in combination with known prostate cancer risk variants, explain 33% of the familial risk for this disease in European-ancestry populations. These findings provide new regions for investigation into the pathogenesis of prostate cancer and demonstrate the usefulness of combining ancestrally diverse populations to discover risk loci for disease.
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- 2014
21. A Prospective Study of Serum 25-Hydroxyvitamin D Levels and Mortality Among African Americans and Non-African Americans
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William J. Blot, Wei Zheng, Qiuyin Cai, Lisa B. Signorello, Sarah S. Cohen, Xijing Han, and Elizabeth L. Cope
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Adult ,Male ,Gerontology ,Epidemiology ,Original Contributions ,vitamin D deficiency ,Cohort Studies ,Cause of Death ,Odds Ratio ,Vitamin D and neurology ,Humans ,Medicine ,Prospective Studies ,Vitamin D ,Prospective cohort study ,Aged ,Cause of death ,business.industry ,Case-control study ,Odds ratio ,Middle Aged ,Vitamin D Deficiency ,medicine.disease ,Southeastern United States ,Black or African American ,Logistic Models ,Quartile ,Case-Control Studies ,Female ,Seasons ,business ,Biomarkers ,Demography ,Cohort study - Abstract
The beneficial biologic effects attributed to vitamin D suggest a potential to influence overall mortality. Evidence addressing this hypothesis is limited, especially for African Americans who have a high prevalence of vitamin D insufficiency. The authors conducted a nested case-control study within the prospective Southern Community Cohort Study to relate baseline serum levels of 25-hydroxyvitamin D (25(OH)D) with subsequent mortality. Cases were 1,852 participants who enrolled from 2002 to 2009 and died >12 months postenrollment. Controls (n = 1,852) were matched on race, sex, age, enrollment site, and blood collection date. The odds ratios for quartile 1 (21.64 ng/mL) levels of 25(OH)D were 1.60 (95% confidence interval (CI): 1.20, 2.14) for African Americans and 2.11 (95% CI: 1.39, 3.21) for non-African Americans. The effects were strongest for circulatory disease death, where quartile 1 versus quartile 4 odds ratios were 2.53 (95% CI: 1.44, 4.46) and 3.25 (95% CI: 1.33, 7.93) for African Americans and non-African Americans, respectively. The estimated odds of total mortality were minimized in the 25(OH)D range of 35–40 ng/mL. These findings provide support for the hypothesis that vitamin D status may have an important influence on mortality for both African Americans and non-African Americans.
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- 2012
22. Identification of 23 new prostate cancer susceptibility loci using the iCOGS custom genotyping array
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Artitaya Lophatananon, W. Ryan Diver, Stig E. Bojesen, Roman Corral, Fredrick R. Schumacher, Stephen J. Chanock, Shannon K. McDonnell, Graham G. Giles, Craig C. Teerlink, Douglas F. Easton, Cezary Cybulski, Brian E. Henderson, Judith A. Clements, Ali Amin Al Olama, Francois Bacot, David P. Dearnaley, Elio Riboli, Peter Klarskov, Daniel Vincent, Rosemary A. Wilkinson, Danielle M. Karyadi, Michelle Guy, Vincent Khoo, Christopher A. Haiman, Afshan Siddiq, M. Andreas Røder, Amit Joshi, Jong Y. Park, Walther Vogel, Henrik Grönberg, Angela Cox, Rudolf Kaaks, Nora Pashayan, Timothy J. Key, C. R. J. Woodhouse, Jarmo Virtamo, Meredith Yeager, Malgorzata Tymrakiewicz, Sune F. Nielsen, Richard B. Hayes, Johanna Schleutker, Gianluca Severi, Robert Huddart, Wei Zheng, Thomas A. Sellers, Melanie Maranian, Shahana Ahmed, David E. Neal, Daniel Leongamornlert, Zsofia Kote-Jarai, Tiina Wahlfors, Loic Le Marchand, Kay-Tee Khaw, Tokhir Dadaev, Lisa A. Cannon-Albright, Janet L. Stanford, William J. Blot, Andy C. H. Lee, Freddie C. Hamdy, Siqun L. Zheng, Rosalind A. Eeles, Alison M. Dunning, Mariana C. Stern, Melissa C. Southey, Don M. Conroy, Kenneth Muir, Ahva Shahabi, Alan Horwich, Gerald L. Andriole, Antje E. Rinckleb, Srilakshmi Srinivasan, Tim Dudderidge, Joe Dennis, Radka Kaneva, Vanio Mitev, Angela Morgan, Sue A. Ingles, Adam S. Kibel, Markus Aly, Koveela Govindasami, Maya Ghoussaini, Jenny L Donovan, Manuel R. Teixeira, Emma J. Sawyer, Sara Lindström, Jiangfeng Xu, Maren Weischer, Ed Dicks, Jyotsna Batra, S Jugurnauth-Little, Hui-Yi Lin, Suzanne Kolb, Lisa B. Signorello, Dallas R. English, Antonis C. Antoniou, Federico Canzian, Anssi Auvinen, Mia M. Gaudet, Paula Paulo, Paul D.P. Pharoah, Heiko Müller, Qiuyin Cai, Børge G. Nordestgaard, Esther M. John, Sonja I. Berndt, D J Schaid, Daniele Campa, Chris Ogden, Colin Cooper, Craig Luccarini, Jan Lubinski, Elaine A. Ostrander, Ruth C. Travis, Dominika Wokołorczyk, John L. Hopper, Sofia Maia, Sara Benlloch, Chris Parker, Erika M. Kwon, Nicholas van As, Caroline Baynes, C. Slavov, Teuvo L.J. Tammela, Ethan M. Lange, Daniel C. Tessier, David J. Hunter, Dietrich Rothenbacher, Robert A. Stephenson, Liesel M. FitzGerald, Christiane Maier, Hermann Brenner, Kathleen A. Cooney, Graham A. Colditz, Felicity Lose, Edward J. Saunders, Demetrius Albanes, Stephen N. Thibodeau, Fredrik Wiklund, Amanda B. Spurdle, Jan Adolfsson, Susan M. Gapstur, Peter Kraft, Bettina F. Drake, and Alan Thompson
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Male ,genetic association ,genotype ,Genome-wide association study ,Bioinformatics ,genetic risk ,developed country ,Prostate cancer ,0302 clinical medicine ,Risk Factors ,Genotype ,Cooperative Behavior ,breast cancer ,cancer prognosis ,cancer susceptibility ,cell adhesion ,cell cycle arrest ,chromosome 14 ,chromosome 2 ,double stranded DNA break ,embryo development ,extracellular matrix ,gene frequency ,gene linkage disequilibrium ,genetic predisposition ,Gleason score ,heterozygote ,human ,intron ,priority journal ,promoter region ,prostate cancer ,quality control ,regulator gene ,Oligonucleotide Array Sequence Analysis ,0303 health sciences ,education.field_of_study ,3. Good health ,030220 oncology & carcinogenesis ,Population ,Single-nucleotide polymorphism ,Biology ,ta3111 ,Polymorphism, Single Nucleotide ,03 medical and health sciences ,Meta-Analysis as Topic ,Genetics ,medicine ,Humans ,Genetic Predisposition to Disease ,education ,Genotyping ,030304 developmental biology ,Case-control study ,Cancer ,Prostatic Neoplasms ,medicine.disease ,ta3122 ,Genetic Loci ,Case-Control Studies ,Genome-Wide Association Study - Abstract
Prostate cancer is the most frequently diagnosed cancer in males in developed countries. To identify common prostate cancer susceptibility alleles, we genotyped 211,155 SNPs on a custom Illumina array (iCOGS) in blood DNA from 25,074 prostate cancer cases and 24,272 controls from the international PRACTICAL Consortium. Twenty-three new prostate cancer susceptibility loci were identified at genome-wide significance (P < 5 × 10(-8)). More than 70 prostate cancer susceptibility loci, explaining ∼30% of the familial risk for this disease, have now been identified. On the basis of combined risks conferred by the new and previously known risk loci, the top 1% of the risk distribution has a 4.7-fold higher risk than the average of the population being profiled. These results will facilitate population risk stratification for clinical studies.
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- 2016
23. A common variant at the TERT-CLPTM1L locus is associated with estrogen receptor-negative breast cancer
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Michael F. Press, Asta Försti, Elisa V. Bandera, Hans-Peter Sinn, David Van Den Berg, Foluso O. Ademuyiwa, Veli-Matti Kosma, Loic Le Marchand, Nicholas G. Martin, Douglas F. Easton, Susan E. Hankinson, Timothy R. Rebbeck, Leslie Bernstein, Florentia Fostira, Jenny Chang-Claude, Andrea Holbrook, Christine B. Ambrosone, Arif B. Ekici, Shahana Ahmed, Laura Baglietto, Stephen J. Chanock, Astrid Irwanto, Regina G. Ziegler, Andrew K. Godwin, Julie R. Palmer, Lucy Xia, Diether Lambrechts, Xin Sheng, Heli Nevanlinna, William J. Tapper, Christopher K. Edlund, Sue A. Ingles, Hans Wildiers, Diana Eccles, Julian Peto, Rudolf Kaaks, Federico Canzian, Els Wauters, Penelope Miron, Daniel O. Stram, Sara Margolin, Afshan Siddiq, Sara Lindström, Thomas Dünnebier, Ian Tomlinson, Gary K. Chen, Matthias W. Beckmann, Wei Zheng, Lisa B. Signorello, Adam M. Lee, Frans B. L. Hogervorst, Grant W. Montgomery, Rebecca Hein, Alison M. Dunning, Rosemary L. Balleine, Athanasios M. Dimopoulos, Loreall Pooler, Eric A. Ross, Arja Jukkola-Vuorinen, Peter A. Fasching, Laurence N. Kolonel, Irene Konstantopoulou, Jianjun Liu, Carl Blomqvist, Timothy G. Lesnick, Graham G. Giles, Lynn Rosenberg, Christine L. Clarke, Arndt Hartmann, Gianluca Severi, Charles M. Perou, Thomas Rüdiger, Sarah J. Nyante, Paul J. Goodfellow, Angela Cox, Esther M. John, Heather Spencer Feigelson, Robert N. Hoover, Fergus J. Couch, Ute Hamann, Daniel I. Chasman, Brian E. Henderson, Celine M. Vachon, Stephan Nickels, Lorraine Durcan, Jane Carpenter, Swati Kulkarni, Xianshu Wang, Susan L. Slager, Jorge L. Rodriguez-Gil, William J. Blot, Elinor J. Sawyer, Isabel dos Santos Silva, JoEllen Weaver, Christopher A. Haiman, S Gerty, Christine D. Berg, Julie E. Buring, Katri Pylkäs, Peggy Wan, Robert B. Diasio, Marjanka K. Schmidt, Nikki Graham, Rüdiger Schulz-Wendtland, Drakoulis Yannoukakos, Jennifer Ivanovich, Nicola F. Johnson, Lisa A. Carey, Hiltrud Brauch, David J. Hunter, Curtis Olswold, Sandra L. Deming, Harsh B. Pathak, Fredrick R. Schumacher, W. Ryan Driver, Robert C. Millikan, Dimitrios Pectasides, George Fountzilas, Simon S. Cross, Dieter Flesch-Janys, Melissa C. Southey, Robert Winqvist, Paul D.P. Pharoah, Dario Greco, Judith Heinz, Jennifer J. Hu, Peter Kraft, Arto Mannermaa, Kristen N. Stevens, and Yon Ko
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Oncology ,medicine.medical_specialty ,Genotype ,medicine.drug_class ,European Continental Ancestry Group ,Estrogen receptor ,Locus (genetics) ,Genome-wide association study ,Breast Neoplasms ,Biology ,Polymorphism, Single Nucleotide ,White People ,Article ,03 medical and health sciences ,Prostate cancer ,0302 clinical medicine ,Breast cancer ,Internal medicine ,Receptors ,medicine ,Genetics ,Humans ,Genetic Predisposition to Disease ,Allele ,Polymorphism ,Telomerase ,030304 developmental biology ,Aged ,African Americans ,0303 health sciences ,Case-Control Studies ,Female ,Genome-Wide Association Study ,Membrane Proteins ,Middle Aged ,Neoplasm Proteins ,Receptors, Estrogen ,Genetic Loci ,Single Nucleotide ,medicine.disease ,Estrogen ,3. Good health ,Black or African American ,030220 oncology & carcinogenesis ,Immunology - Abstract
Estrogen receptor (ER)-negative breast cancer shows a higher incidence in women of African ancestry compared to women of European ancestry. In search of common risk alleles for ER-negative breast cancer, we combined genome-wide association study (GWAS) data from women of African ancestry (1,004 ER-negative cases and 2,745 controls) and European ancestry (1,718 ER-negative cases and 3,670 controls), with replication testing conducted in an additional 2,292 ER-negative cases and 16,901 controls of European ancestry. We identified a common risk variant for ER-negative breast cancer at the TERT-CLPTM1L locus on chromosome 5p15 (rs10069690: per-allele odds ratio (OR) = 1.18 per allele, P = 1.0 × 10(-10)). The variant was also significantly associated with triple-negative (ER-negative, progesterone receptor (PR)-negative and human epidermal growth factor-2 (HER2)-negative) breast cancer (OR = 1.25, P = 1.1 × 10(-9)), particularly in younger women (
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- 2016
24. Characterizing Genetic Susceptibility to Breast Cancer in Women of African Ancestry
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Ye Feng, Esther M. John, Christine B. Ambrosone, Sarah J. Nyante, Yonglan Zheng, Jeannette T. Bensen, Stephen J. Chanock, William J. Blot, Sue A. Ingles, Adeyinka G. Falusi, Sandra L. Deming, Dezheng Huo, Julie R. Palmer, Leslie Bernstein, Edward A. Ruiz-Narváez, Clement Adebamowo, Gerhard A. Coetzee, Laurence N. Kolonel, Timothy R. Rebbeck, Andrew F. Olshan, Lara E. Sucheston-Campbell, Michael F. Press, Lisa B. Signorello, Stephen A. Haddad, Kathryn L. Lunetta, Olufunmilayo I. Olopade, Song Yao, Temidayo O. Ogundiran, Oladosu Ojengbede, Jennifer J. Hu, David V. Conti, Daniel O. Stram, Anselm Hennis, Wei Zheng, Qiuyin Cai, Katherine L. Nathanson, Suhn K. Rhie, Elisa V. Bandera, Stefan Ambs, Yoo Jeong Han, Christopher A. Haiman, Barbara Nemesure, Loic Le Marchand, Jorge L. Rodriguez-Gil, and Regina G. Ziegler
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0301 basic medicine ,Linkage disequilibrium ,Epidemiology ,Breast Neoplasms ,Biology ,Polymorphism, Single Nucleotide ,Article ,03 medical and health sciences ,Breast cancer ,Risk Factors ,medicine ,Genetic predisposition ,Biomarkers, Tumor ,Humans ,Genetic Predisposition to Disease ,Allele ,Alleles ,Genetic association ,Genetics ,Cancer ,Chromosome Mapping ,medicine.disease ,Black or African American ,030104 developmental biology ,Oncology ,TOX3 ,Receptors, Estrogen ,Genetic marker ,Genetic Loci ,Case-Control Studies ,Female - Abstract
Background: Genome-wide association studies have identified approximately 100 common genetic variants associated with breast cancer risk, the majority of which were discovered in women of European ancestry. Because of different patterns of linkage disequilibrium, many of these genetic markers may not represent signals in populations of African ancestry. Methods: We tested 74 breast cancer risk variants and conducted fine-mapping of these susceptibility regions in 6,522 breast cancer cases and 7,643 controls of African ancestry from three genetic consortia (AABC, AMBER, and ROOT). Results: Fifty-four of the 74 variants (73%) were found to have ORs that were directionally consistent with those previously reported, of which 12 were nominally statistically significant (P < 0.05). Through fine-mapping, in six regions (3p24, 12p11, 14q13, 16q12/FTO, 16q23, 19p13), we observed seven markers that better represent the underlying risk variant for overall breast cancer or breast cancer subtypes, whereas in another two regions (11q13, 16q12/TOX3), we identified suggestive evidence of signals that are independent of the reported index variant. Overlapping chromatin features and regulatory elements suggest that many of the risk alleles lie in regions with biological functionality. Conclusions: Through fine-mapping of known susceptibility regions, we have revealed alleles that better characterize breast cancer risk in women of African ancestry. Impact: The risk alleles identified represent genetic markers for modeling and stratifying breast cancer risk in women of African ancestry. Cancer Epidemiol Biomarkers Prev; 26(7); 1016–26. ©2017 AACR.
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- 2016
25. Prostate Cancer Susceptibility in Men of African Ancestry at 8q24
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Fredrick R. Schumacher, Dennis J. Hazelett, Anslem J.M. Hennis, Suh Yuh Wu, Xin Sheng, David V. Conti, Dominique Quinque, Brian E. Henderson, Sara S. Strom, Sue A. Ingles, Yao Tettey, Richard B. Biritwum, Bogdan Pasaniuc, Graham Casey, Lisa B. Signorello, Edward D. Yeboah, Shelley Niwa, Anand P. Chokkalingam, Sonja I. Berndt, John D. Carpten, Michael G. Rosenfeld, Stephen J. Chanock, Phyllis J. Goodman, Ying Han, Wei Zheng, Alex Lubwama, M. Cristina Leske, Dimple Notani, Ann W. Hsing, Andrew A. Adjei, Susan M. Gapstur, William J. Blot, Janet L. Stanford, Stephen Watya, Evelyn Tay, Michael B. Cook, Loreall Pooler, Christopher A. Haiman, Victoria L. Stevens, Benjamin A. Rybicki, Lisa Chu, Barbara Nemesure, Ann Truelove, Nadin Rohland, Christine Neslund-Dudas, William B. Isaacs, John S. Witte, Alex Allen, Adam B. Murphy, Suzanne Kolb, Swapan Mallick, David Reich, Rick A. Kittles, Esther M. John, Jianfeng Xu, S. Lilly Zheng, Ranveer Singh Jayani, Gerhard A. Coetzee, Zhaoming Wang, Arti Tandon, Eric A. Klein, Kristin A. Rand, Daniel O. Stram, and Curtis A. Pettaway
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0301 basic medicine ,Oncology ,Male ,Cancer Research ,Aging ,Prostate cancer ,Prostate ,80 and over ,2.1 Biological and endogenous factors ,Aetiology ,Cancer ,Aged, 80 and over ,Prostate Cancer ,PROSTATE CANCER SUSCEPTIBILITY ,Single Nucleotide ,Middle Aged ,Control subjects ,medicine.anatomical_structure ,Pair 8 ,RNA, Long Noncoding ,Long Noncoding ,Chromosomes, Human, Pair 8 ,Human ,Urologic Diseases ,medicine.medical_specialty ,Oncology and Carcinogenesis ,Brief Communication ,Polymorphism, Single Nucleotide ,Chromosomes ,03 medical and health sciences ,Clinical Research ,Internal medicine ,medicine ,Genetics ,Humans ,Genetic Predisposition to Disease ,Oncology & Carcinogenesis ,Polymorphism ,Aged ,business.industry ,Prevention ,Human Genome ,Case-control study ,Prostatic Neoplasms ,Odds ratio ,medicine.disease ,Confidence interval ,United States ,Black or African American ,030104 developmental biology ,Case-Control Studies ,Risk allele ,RNA ,business - Abstract
The 8q24 region harbors multiple risk variants for distinct cancers, including >8 for prostate cancer. In this study, we conducted fine mapping of the 8q24 risk region (127.8-128.8Mb) in search of novel associations with common and rare variation in 4853 prostate cancer case patients and 4678 control subjects of African ancestry. All statistical tests were two-sided. We identified three independent associations at P values of less than 5.00×10(-8), all of which were replicated in studies from Ghana and Uganda (combined sample = 5869 case patients, 5615 control subjects; rs114798100: risk allele frequency [RAF] = 0.04, per-allele odds ratio [OR] = 2.31, 95% confidence interval [CI] = 2.04 to 2.61, P = 2.38×10(-40); rs72725879: RAF = 0.33, OR = 1.37, 95% CI = 1.30 to 1.45, P = 3.04×10(-27); and rs111906932: RAF = 0.03, OR = 1.79, 95% CI = 1.53 to 2.08, P = 1.39×10(-13)). Risk variants rs114798100 and rs111906923 are only found in men of African ancestry, with rs111906923 representing a novel association signal. The three variants are located within or near a number of prostate cancer-associated long noncoding RNAs (lncRNAs), including PRNCR1, PCAT1, and PCAT2. These findings highlight ancestry-specific risk variation and implicate prostate-specific lncRNAs at the 8q24 prostate cancer susceptibility region.
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- 2016
26. A prospective study of Trichomonas vaginalis and prostate cancer risk among African American men
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John F. Alderete, Lisa B. Signorello, William J. Blot, Xijing Han, Jay H. Fowke, and Kelvin A. Moses
- Subjects
Adult ,Male ,medicine.medical_specialty ,Race ,Short Report ,Antibodies, Protozoan ,Trichomonas Infections ,Trichomonas Infection ,Comorbidity ,medicine.disease_cause ,Risk Assessment ,General Biochemistry, Genetics and Molecular Biology ,Host-Parasite Interactions ,03 medical and health sciences ,0302 clinical medicine ,Risk Factors ,Internal medicine ,Trichomonas vaginalis ,medicine ,Humans ,Prospective Studies ,030212 general & internal medicine ,Prospective cohort study ,Aged ,Medicine(all) ,Gynecology ,Prostate cancer ,Biochemistry, Genetics and Molecular Biology(all) ,business.industry ,Incidence ,Incidence (epidemiology) ,Case-control study ,Prostatic Neoplasms ,General Medicine ,Middle Aged ,medicine.disease ,United States ,3. Good health ,Black or African American ,Case-Control Studies ,030220 oncology & carcinogenesis ,Risk assessment ,business ,Cohort study - Abstract
Background African Americans (AA) have a higher prevalence of Trichomonas vaginalis (Tv) infection and a higher prostate (PC) risk. Past studies suggest an association between Tv seropositivity and PC, and therefore we prospectively investigated this association among AA men. Results Incident PC cases were individually matched to controls in a nested case–control study within the Southern Community Cohort Study (SCCS). Primary analysis included 296 PC cases and 497 race-matched controls. Levels of Tv antibody response were measured by ELISA in serum collected at baseline. Tv antibody response did not significantly differ between cases and controls overall or within AA participants (253 AA cases). There were no significant associations or trends between levels of Tv response and PC risk or the diagnosis of aggressive PC. Conclusion We found no evidence of a prospective association between baseline Tv infection and PC risk in AA men. Tv infection in men may have substantial health implications in HIV transmission and reproductive outcomes, but may not impact future PC risk in AA men at high-risk for PC. Further efforts need to define past vs. present Tv infection and to separate pathophysiology from PC detection.
- Published
- 2016
27. MP39-13 BASELINE PROSTATE-SPECIFIC ANTIGEN (PSA) LEVELS IN MIDLIFE PREDICT TOTAL AND AGGRESSIVE PROSTATE CANCER IN AFRICAN-AMERICAN MEN
- Author
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Quoc-Dien Trinh, Sigrid Carlsson, Andrew J. Vickers, Daniel Sjöberg, Adam S. Kibel, Mark A. Preston, Travis Gerke, Mark Steinwandel, Kathryn M. Wilson, Lorelei A. Mucci, Hans Lilja, and Lisa B. Signorello
- Subjects
Oncology ,Prostate-specific antigen ,medicine.medical_specialty ,Prostate cancer ,business.industry ,Urology ,Internal medicine ,Medicine ,African american men ,business ,medicine.disease ,Baseline (configuration management) - Published
- 2016
28. An intergenic risk locus containing an enhancer deletion in 2q35 modulates breast cancer risk by deregulating IGFBP5 expression
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Melissa C. Southey, Daniel Klevebring, Robert Winqvist, Irene L. Andrulis, Keitaro Matsuo, Anna Jakubowska, Susan L. Neuhausen, Paul D.P. Pharoah, Natalia Bogdanova, Lisa B. Signorello, Annika Lindblom, Kamila Czene, Drakoulis Yannoukakos, Caroline Seynaeve, Asaf Wyszynski, Michael D. Cole, John L. Hopper, kConFab Investigators, Elinor J. Sawyer, Qin Wang, Vessela N. Kristensen, Hidemi Ito, Paolo Radice, Daehee Kang, Sara Margolin, Hermann Brenner, Annegien Broeks, William J. Blot, Yu-Tang Gao, Mitul Shah, Matthias W. Beckmann, Wei Zheng, Brian E. Henderson, Peter Devilee, Javier Benitez, David Van Den Berg, Christopher A. Haiman, Thilo Dörk, Hatef Darabi, Ans M.W. van den Ouweland, Alfons Meindl, Frederik Marmé, Jacques Simard, Isabel dos-Santos-Silva, Jan Lubinski, Pei-Ei Wu, Veli-Matti Kosma, Katri Pylkäs, Mikael Hartman, Soo-Hwang Teo, Tien Yin Wong, Suleeporn Sangrajrang, Paolo Peterlongo, Douglas F. Easton, James McKay, Fergus J. Couch, Angela Cox, Maartje J. Hooning, Ji Yeob Choi, Anja Rudolph, Arto Mannermaa, Anna H. Wu, Ute Hamann, Montserrat Garcia-Closas, Christine B. Ambrosone, Janet E. Olson, Hiltrud Brauch, Rita K. Schmutzler, Julian Peto, Manjeet K. Bolla, Alison M. Dunning, Heli Nevanlinna, Børge G. Nordestgaard, Hui Miao, Yali Zhang, Kenneth Muir, Barbara Burwinkel, Nick Orr, Aida Karina Dieffenbach, Marjanka K. Schmidt, Jirong Long, Martine Dumont, Jenny Chang-Claude, Kristin Lam, Chen-Yang Shen, Anthony J. Swerdlow, Chi-Chen Hong, Peter A. Fasching, Stig E. Bojesen, Diether Lambrechts, Xiao-Ou Shu, Graham G. Giles, Christopher I. Amos, Joe Dennis, Hans Wildiers, Christian Lytle, Sofia Khan, Pascal Guénel, Elisa V. Bandera, Artitaya Lophatananon, Georgia Chenevix-Trench, Kyriaki Michailidou, Song Yao, Roger L. Milne, Anna González-Neira, Ian Tomlinson, Thérèse Truong, Amanda E. Toland, Per Hall, Jonine D. Figueroa, Julia A. Knight, Clinical Genetics, Obstetrics & Gynecology, Medical Oncology, Wang, Jean [0000-0002-9139-0627], Dennis, Joe [0000-0003-4591-1214], Pharoah, Paul [0000-0001-8494-732X], Dunning, Alison [0000-0001-6651-7166], Easton, Douglas [0000-0003-2444-3247], and Apollo - University of Cambridge Repository
- Subjects
0301 basic medicine ,Adult ,Locus (genetics) ,Genome-wide association study ,Breast Neoplasms ,Biology ,Polymorphism, Single Nucleotide ,03 medical and health sciences ,Young Adult ,Breast cancer ,SDG 3 - Good Health and Well-being ,Genotype ,Genetics ,medicine ,Medicine and Health Sciences ,Humans ,Genetic Predisposition to Disease ,Copy-number variation ,Enhancer ,Promoter Regions, Genetic ,Molecular Biology ,Genetics (clinical) ,Genetic association ,Aged ,Sequence Deletion ,Association Studies Articles ,Case-control study ,General Medicine ,Middle Aged ,medicine.disease ,3. Good health ,Gene Expression Regulation, Neoplastic ,030104 developmental biology ,Enhancer Elements, Genetic ,Case-Control Studies ,Chromosomes, Human, Pair 2 ,MCF-7 Cells ,Female ,Carrier Proteins ,Insulin-Like Growth Factor Binding Protein 5 - Abstract
Breast cancer is the most diagnosed malignancy and the second leading cause of cancer mortality in females. Previous association studies have identified variants on 2q35 associated with the risk of breast cancer. To identify functional susceptibility loci for breast cancer, we interrogated the 2q35 gene desert for chromatin architecture and functional variation correlated with gene expression. We report a novel intergenic breast cancer risk locus containing an enhancer copy number variation (enCNV; deletion) located approximately 400Kb upstream to IGFBP5, which overlaps an intergenic ERα-bound enhancer that loops to the IGFBP5 promoter. The enCNV is correlated with modified ERα binding and monoallelic-repression of IGFBP5 following oestrogen treatment. We investigated the association of enCNV genotype with breast cancer in 1,182 cases and 1,362 controls, and replicate our findings in an independent set of 62,533 cases and 60,966 controls from 41 case control studies and 11 GWAS. We report a dose-dependent inverse association of 2q35 enCNV genotype (percopy OR = 0.68 95%CI 0.55-0.83, P = 0.0002; replication OR = 0.77 95% CI 0.73-0.82, P = 2.1 × 10-19) and identify 13 additional linked variants (r2 > 0.8) in the 20Kb linkage block containing the enCNV (P = 3.2 × 10-15 - 5.6 × 10-17). These associations were independent of previously reported 2q35 variants, rs13387042/rs4442975 and rs16857609, and were stronger for ER-positive than ER-negative disease. Together, these results suggest that 2q35 breast cancer risk loci may be mediating their effect through IGFBP5.
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- 2016
29. Prevalence and Correlates of Complementary and Alternative Medicine Services Use in Low-Income African Americans and Whites: A Report from the Southern Community Cohort Study
- Author
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Yong Cui, William J. Blot, Margaret K. Hargreaves, Donna Kenerson, Jianguo Liu, Xiao-Ou Shu, and Lisa B. Signorello
- Subjects
Adult ,Complementary Therapies ,Male ,Gerontology ,Alcohol Drinking ,Health Status ,Population ,MEDLINE ,Logistic regression ,White People ,Humans ,Medicine ,education ,Poverty ,Aged ,Family Characteristics ,education.field_of_study ,business.industry ,Smoking ,Original Articles ,Odds ratio ,Middle Aged ,Patient Acceptance of Health Care ,United States ,Confidence interval ,Educational attainment ,Black or African American ,Logistic Models ,Socioeconomic Factors ,Complementary and alternative medicine ,Chronic Disease ,Income ,Educational Status ,Female ,business ,Demography ,Cohort study - Abstract
This study aimed to examine the prevalence, trends, and correlates of practitioner-based complementary and alternative medicine (CAM) services use according to race in a socioeconomically disadvantaged population.Included in this cross-sectional analysis were 50,176 African Americans (AAs) and 19,038 whites enrolled into the Southern Community Cohort Study from March 2002 through September 2009. Logistic regression models were used to calculate odds ratios (ORs) and 95% confidence intervals (CIs) of CAM services use associated with participant characteristics.Outcomes include the prevalence of and trends in use of CAM services during 2002-2009 and correlates of use by race.CAM services use during 2002-2009 was greater among whites (11.7%) than among AAs (8.5%), but no significant temporal trends within the 8-year period were observed. The significant associations were observed for CAM services use with higher educational attainment (OR 1.78, 95% CI: 1.61-1.96 for college versus less than high school), household income (OR 1.61, 95% CI: 1.44-1.81 for ≥$50,000 versus$15,000), and having a history of a chronic disease (OR 1.34, 95% CI: 1.21-1.47) among both AAs and whites. Significant differences in findings between AAs and whites were seen for age (with a sharp decline in use with older age among AAs but not whites), sex (with the excess of female users more striking among whites), employment (with the unemployed among AAs but not whites more likely to be users), alcohol consumption (with white but not AA drinkers more likely to report CAM services use), and cigarette smoking status (with negative association of use with current smokers more striking among whites).CAM services use is associated with sociodemographic and health-related factors, and racial differences in such use exist. The descriptive findings of this study help supplement the limited information on CAM use among low-income and minority populations in the United States.
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- 2012
30. A genome-wide association study of breast cancer in women of African ancestry
- Author
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Carolyn M. Hutter, Olufunmilayo I. Olopade, Clement Adebamowo, Jirong Long, Michael S. Simon, Christine B. Ambrosone, Xin Sheng, Sandra L. Deming, Esther M. John, Elisa V. Bandera, Stephen J. Chanock, Laurence N. Kolonel, Gary K. Chen, Brian E. Henderson, Edward A. Ruiz-Narváez, Suhn K. Rhie, William J. Blot, Stefan Ambs, Robert C. Millikan, David Van Den Berg, Loreall Pooler, Wei Zheng, Lisa B. Signorello, Timothy R. Rebbeck, Angela DeMichele, Regina G. Ziegler, Yonglan Zheng, Sue A. Ingles, Leslie Bernstein, Sarah J. Nyante, Alicia Young, Qiuyin Cai, Daniel O. Stram, Jorge L. Rodriguez-Gil, Anselm Hennis, Nancy J. Cox, Suh Yuh Wu, Katherine L. Nathanson, Michael F. Press, Fang Chen, M. Cristina Leske, Susan M. Domchek, Guoliang Li, Ulrike Peters, Christopher A. Haiman, Barbara Nemesure, Loic Le Marchand, Peggy Wan, Temidayo O. Ogundiran, Jennifer J. Hu, Dezheng Huo, Julie R. Palmer, and Charles Kooperberg
- Subjects
Adult ,Black People ,Breast Neoplasms ,Genome-wide association study ,Single-nucleotide polymorphism ,Biology ,Polymorphism, Single Nucleotide ,Article ,Cohort Studies ,Young Adult ,Breast cancer ,Risk Factors ,Polymorphism (computer science) ,Genetics ,medicine ,Humans ,Genetic Predisposition to Disease ,Young adult ,Genotyping ,Genetics (clinical) ,Aged ,Genetic association ,Aged, 80 and over ,Case-control study ,Middle Aged ,medicine.disease ,Black or African American ,Case-Control Studies ,Female ,Genome-Wide Association Study - Abstract
Genome-wide association studies (GWAS) in diverse populations are needed to reveal variants that are more common and/or limited to defined populations. We conducted a GWAS of breast cancer in women of African ancestry, with genotyping of1,000,000 SNPs in 3,153 African American cases and 2,831 controls, and replication testing of the top 66 associations in an additional 3,607 breast cancer cases and 11,330 controls of African ancestry. Two of the 66 SNPs replicated (p0.05) in stage 2, which reached statistical significance levels of 10(-6) and 10(-5) in the stage 1 and 2 combined analysis (rs4322600 at chromosome 14q31: OR = 1.18, p = 4.3 × 10(-6); rs10510333 at chromosome 3p26: OR = 1.15, p = 1.5 × 10(-5)). These suggestive risk loci have not been identified in previous GWAS in other populations and will need to be examined in additional samples. Identification of novel risk variants for breast cancer in women of African ancestry will demand testing of a substantially larger set of markers from stage 1 in a larger replication sample.
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- 2012
31. Evaluation of a Questionnaire to Assess Sedentary and Active Behaviors in the Southern Community Cohort Study
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Sarah S. Cohen, Charles E. Matthews, Jay H. Fowke, David G. Schlundt, Lisa B. Signorello, Maciej S. Buchowski, William J. Blot, and Margaret K. Hargreaves
- Subjects
Adult ,Male ,Gerontology ,Low income ,Time Factors ,Wilcoxon signed-rank test ,Health Behavior ,Physical activity ,Article ,White People ,Surveys and Questionnaires ,Criterion validity ,Humans ,Medicine ,Orthopedics and Sports Medicine ,Prospective Studies ,Prospective cohort study ,Exercise ,Life Style ,Aged ,Life style ,business.industry ,Reproducibility of Results ,Health Status Disparities ,Middle Aged ,Southeastern United States ,Black or African American ,Cohort ,Female ,business ,Cohort study - Abstract
Background: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.Methods: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.Results: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.Conclusions: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.
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- 2012
32. Obesity and All-Cause Mortality Among Black Adults and White Adults
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William J. Blot, Wei Zheng, Sarah S. Cohen, Lisa B. Signorello, Elizabeth L. Cope, Margaret K. Hargreaves, and Joseph K. McLaughlin
- Subjects
Adult ,Male ,Gerontology ,Epidemiology ,Original Contributions ,White People ,Body Mass Index ,Cause of Death ,medicine ,Humans ,Obesity ,Prospective Studies ,Prospective cohort study ,Aged ,Proportional Hazards Models ,business.industry ,Proportional hazards model ,Hazard ratio ,Middle Aged ,medicine.disease ,Southeastern United States ,Confidence interval ,Black or African American ,Cohort ,Female ,Self Report ,business ,Body mass index ,Follow-Up Studies ,Demography ,Cohort study - Abstract
In recent pooled analyses among whites and Asians, mortality was shown to rise markedly with increasing body mass index (BMI; weight (kg)/height (m)(2)), but much less is known about this association among blacks. This study prospectively examined all-cause mortality in relation to BMI among 22,014 black males, 9,343 white males, 30,810 black females, and 14,447 white females, aged 40-79 years, from the Southern Community Cohort Study, an epidemiologic cohort of largely low-income participants in 12 southeastern US states. Participants enrolled in the cohort from 2002 to 2009 and were followed up to 8.9 years. Hazard ratios and 95% confidence intervals for mortality were obtained from sex- and race-stratified Cox proportional hazards models in association with BMI at cohort entry, adjusting for age, education, income, cigarette smoking, and alcohol consumption. Elevated BMI was associated with increased mortality among whites (hazard ratios for BMI >40 vs. 20-24.9 = 1.37 (95% confidence interval (CI): 1.02, 1.84) and 1.47 (95% CI: 1.15, 1.89) for white males and white females, respectively) but not significantly among blacks (hazard ratios = 1.13 (95% CI: 0.89, 1.43) and 0.87 (95% CI: 0.72, 1.04) for black males and black females, respectively). In this large cohort, obesity in mid-to-late adulthood among blacks was not associated with the same excess mortality risk seen among whites.
- Published
- 2012
33. Detectable clonal mosaicism from birth to old age and its relationship to cancer
- Author
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William J. Blot, Christopher I. Amos, Cynthia Regnier, Sara S. Strom, David R. Crosslin, Nadia N. Hansel, Janey L. Wiggs, Cathy C. Laurie, Andrew McDavid, Cecelia A. Laurie, Karl C. Desch, Eleanor Feingold, Kimberly F. Doheny, Lynn R. Goldin, Laura J. Bierut, Jun-Jun Li, Xiuwen Zheng, Hua Ling, Bruce S. Weir, Sarah M. Hartz, Lisa B. Signorello, Jeffrey C. Murray, Jeffrey E. Lee, Rasika A. Mathias, Louis R. Pasquale, Jenna Udren, Kristine R. Monroe, Ingo Ruczinski, Andrew Crenshaw, Bjarke Feenstra, Leila R. Zelnick, Maria Teresa Landi, Neil E. Caporaso, Teri A. Manolio, Kurt N. Hetrick, Terri H. Beaty, Kenneth Rice, Elizabeth W. Pugh, M. Geoffrey Hayes, Robert B. Scharpf, Sarah C. Nelson, Jae H. Kang, Sue A. Ingles, Venkatraman E. Seshan, Sonja I. Berndt, Matthew P. Conomos, Christopher A. Haiman, Li-E Wang, Gail P. Jarvik, Alan F. Scott, David Ginsburg, Loic Le Marchand, Stephen J. Chanock, Mads Melbye, Jess Shen, Brian E. Henderson, John A. Heit, Daniel B. Mirel, David M. Levine, Kathleen C. Barnes, Siiri N. Bennett, William L. Lowe, Qingyi Wei, Sebastian M. Armasu, Patrick J. Heagerty, Denise Daley, Nataliya Sharopova, Neal D. Freedman, Mariza de Andrade, Anastasia L. Wise, Mary L. Marazita, Stephanie M. Gogarten, and Caitlin P. McHugh
- Subjects
Adult ,Male ,Aging ,Adolescent ,DNA Copy Number Variations ,Physiology ,Genome-wide association study ,Biology ,Article ,03 medical and health sciences ,0302 clinical medicine ,Neoplasms ,Genetics ,medicine ,Humans ,Child ,Gene ,Aged ,030304 developmental biology ,Genetic association ,Aged, 80 and over ,Chromosome Aberrations ,0303 health sciences ,Mosaicism ,Infant, Newborn ,Chromosome Mapping ,Infant ,Cancer ,Karyotype ,Middle Aged ,medicine.disease ,Confidence interval ,Uniparental disomy ,3. Good health ,Child, Preschool ,030220 oncology & carcinogenesis ,Female ,Genome-Wide Association Study ,SNP array - Abstract
Clonal mosaicism for large chromosomal anomalies (duplications, deletions and uniparental disomy) was detected using SNP microarray data from over 50,000 subjects recruited for genome-wide association studies. This detection method requires a relatively high frequency of cells (>5–10%) with the same abnormal karyotype (presumably of clonal origin) in the presence of normal cells. The frequency of detectable clonal mosaicism in peripheral blood is low (
- Published
- 2012
34. Obesity and colorectal cancer screening among black and white adults
- Author
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William J. Blot, Sarah S. Cohen, Harvey J. Murff, and Lisa B. Signorello
- Subjects
Male ,Oncology ,Gerontology ,Cancer Research ,medicine.medical_specialty ,Colorectal cancer ,Large population ,Black People ,Article ,White People ,Body Mass Index ,Cohort Studies ,Internal medicine ,medicine ,Humans ,Obesity ,Sigmoidoscopy ,Early Detection of Cancer ,Aged ,White (horse) ,business.industry ,Colonoscopy ,Middle Aged ,medicine.disease ,Cross-Sectional Studies ,Colorectal cancer screening ,Female ,Colorectal Neoplasms ,business ,Body mass index - Abstract
To examine whether body mass index is associated with reduced colorectal cancer (CRC) screening in a large population of black and white adults.Cross-sectional data collected at baseline for 9,547 black men, 14,515 black women, 3,519 white men, and 7,245 white women aged 50-79 enrolled in the Southern Community Cohort Study from 2002 to 2009 were used to examine odds ratios (OR) with 95 % confidence intervals (CI) for the use of colonoscopy or sigmoidoscopy in relation to body mass index (BMI) categories (18.5, 18.5-24.9 (referent), 25-29.9, 30-34.9, 35-39.9, and 40+ (extreme obesity), kg/m(2)) using logistic regression controlling for age, education, income, health insurance status, last physician visit, cigarette smoking, and alcohol consumption.Increased BMI was not associated with reduced CRC screening among whites (OR (95 % CI) for BMI ≥ 40 = 1.02 (0.71-1.46) for white men and 0.99 (0.83-1.19) for white women), and odds of CRC screening were increased with high BMI among blacks (OR (95 % CI) for BMI ≥ 40 = 1.34 (1.03-1.74) for black men and 1.13 (0.98-1.29) for black women). Extreme obesity was associated with reduced odds of CRC screening only among white women in subgroup analyses limited to those with health insurance or income ≥$25,000/year.Elevated BMI was not a deterrent to CRC screening overall in this population. In light of low overall screening rates for colorectal cancer nationally, efforts to increase screening in all individuals should remain the focus of public health initiatives.
- Published
- 2012
35. Mortality Experience of a Low-Income Population With Young-Onset Diabetes
- Author
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Michael E. May, Baqiyyah Conway, Lisa B. Signorello, and William J. Blot
- Subjects
Adult ,Male ,medicine.medical_specialty ,Endocrinology, Diabetes and Metabolism ,medicine.medical_treatment ,Population ,030209 endocrinology & metabolism ,Coronary Artery Disease ,Disease ,Coronary artery disease ,03 medical and health sciences ,0302 clinical medicine ,Diabetes mellitus ,Internal medicine ,Internal Medicine ,medicine ,Humans ,030212 general & internal medicine ,Epidemiology/Health Services Research ,Age of Onset ,education ,Poverty ,Original Research ,Aged ,Cause of death ,Advanced and Specialized Nursing ,education.field_of_study ,business.industry ,Proportional hazards model ,Insulin ,Hazard ratio ,Middle Aged ,medicine.disease ,3. Good health ,Surgery ,Diabetes Mellitus, Type 1 ,Kidney Failure, Chronic ,Female ,business - Abstract
OBJECTIVE In young-onset diabetes, insulin therapy status is a rough marker of diabetes type. We describe the mortality experience of a low-income, predominantly minority population with diabetes diagnosed before age 30 years, stratified by insulin therapy. RESEARCH DESIGN AND METHODS A total of 1,098 adults aged 40–79 years (median 49) diagnosed with diabetes before age 30 years and 49,914 without diabetes were recruited from community health centers. Individuals with diabetes were categorized by insulin therapy at baseline: group A, insulin therapy only; group B, insulin therapy and an oral hypoglycemic agent; and group C, no insulin therapy. Cox models were used to compute hazard ratios (HRs) and 95% CI for cause-specific mortality based on both underlying and contributing causes of death from death certificates. RESULTS During follow-up (mean 3.9 years), 15.0, 12.5, and 7.3% of groups A, B, and C, respectively, and 4.6% without diabetes died. Compared with individuals without diabetes, HRs (CI) for all-cause mortality were 4.3 (3.4–5.6), 4.2 (2.8–6.3), and 2.0 (1.4–2.8) in groups A, B, and C, respectively. The leading cause of death was renal failure (end-stage renal disease [ESRD]) in group A, ESRD and coronary artery disease (CAD) in group B, and CAD in group C and individuals without diabetes. HRs for these conditions were at least twice as high as the HRs for all-cause mortality, reaching 17.3 (10.2–29.3), 17.9 (8.3–38.7), and 5.1 (2.3–11.7) in groups A, B, and C, respectively, for ESRD. CONCLUSIONS Excess mortality persists among people with young-onset diabetes of long duration, with ESRD and CAD as the leading contributors to mortality.
- Published
- 2012
36. Congenital Anomalies in the Children of Cancer Survivors: A Report From the Childhood Cancer Survivor Study
- Author
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John J. Mulvihill, John Whitton, Rita E. Weathers, Lisa B. Signorello, Marilyn Stovall, John D. Boice, Daniel M. Green, Ann C. Mertens, Leslie L. Robison, and Heather M. Munro
- Subjects
Adult ,Male ,Cancer Research ,Pediatrics ,medicine.medical_specialty ,Adolescent ,Offspring ,medicine.medical_treatment ,Childhood Cancer Survivor Study ,Congenital Abnormalities ,Cohort Studies ,Young Adult ,Risk Factors ,Neoplasms ,medicine ,Humans ,Survivors ,Young adult ,Child ,Retrospective Studies ,business.industry ,Infant ,Cancer ,Retrospective cohort study ,ORIGINAL REPORTS ,Odds ratio ,medicine.disease ,Radiation therapy ,Oncology ,Child, Preschool ,Female ,business ,Cohort study - Abstract
Purpose Children with cancer receive mutagenic treatments, which raises concern about the potential transmissibility of germline damage to their offspring. This question has been inadequately studied to date because of a lack of detailed individual treatment exposure assessment such as gonadal radiation doses. Methods Within the Childhood Cancer Survivor Study, we performed a retrospective cohort analysis of validated cases of congenital anomalies among 4,699 children of 1,128 male and 1,627 female childhood cancer survivors. We quantified chemotherapy with alkylating agents and radiotherapy doses to the testes and ovaries and related these exposures to risk of congenital anomalies using logistic regression. Results One hundred twenty-nine children had at least one anomaly (prevalence = 2.7%). For children whose mothers were exposed to radiation or alkylating agents versus neither, the prevalence of anomalies was 3.0% versus 3.5% (P = .51); corresponding figures were 1.9% versus 1.7% (P = .79) for the children of male survivors. Neither ovarian radiation dose (mean, 1.19 Gy; odds ratio [OR] = 0.59; 95% CI, 0.20 to 1.75 for 2.50+ Gy) nor testicular radiation dose (mean, 0.48 Gy; OR = 1.01; 95% CI, 0.36 to 2.83 for 0.50+ Gy) was related to risk of congenital anomalies. Treatment with alkylating agents also was not significantly associated with anomalies in the children of male or female survivors. Conclusion Our findings offer strong evidence that the children of cancer survivors are not at significantly increased risk for congenital anomalies stemming from their parent's exposure to mutagenic cancer treatments. This information is important for counseling cancer survivors planning to have children.
- Published
- 2012
37. Scientific Aspects of Weight Management
- Author
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Claudia Arriaga, Rashmi Ranjan Das, Susan L. Prescott, Günter Weiss, Satz Mengensatzproduktion, Sarah S. Cohen, Ahmad Reza Dorosty, Yongsoon Park, Dong Won Byun, Hyoun-Jung Moon, Alireza Ostadrahimi, Ibrahim Elmadfa, Yi-Chia Huang, Noel W. Solomons, Abdolrasoul Safaeiyan, Jay H. Fowke, Maciej S. Buchowski, Niki A. Georgiou, Druck Reinhardt Druck Basel, Tae-Hee Kim, Tirang R. Neyestani, James Cheng-Chung Wei, Mohammad Alizadeh, Jo J.M. Marx, Sylvia Kroll, John Sinn, Stewart Forsyth, Anna Nowak-Wegrzyn, Monica N Orozco, Wei Zheng, Der Jinn Wu, Rassul Estakhri, Margaret K. Hargreaves, William J. Blot, Aida Ghaffari, Bahram Pourghassem Gargari, Sevana Daneghian, Mitra Abtahi, Klaus Schümann, Ping-Ting Lin, Charles E. Matthews, Lisa B. Signorello, Qiuyin Cai, Saeid Sadeghian, Maria-Eugenia Romero-Abal, Shih-Chien Huang, and Hamed Pouraram
- Subjects
Gerontology ,Nutrition and Dietetics ,business.industry ,Weight management ,Medicine (miscellaneous) ,Medicine ,business - Published
- 2012
38. Sleep duration and breast cancer risk among black and white women
- Author
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William J. Blot, Qian Xiao, Sarah S. Cohen, Louise A. Brinton, Charles E. Matthews, and Lisa B. Signorello
- Subjects
medicine.medical_specialty ,Population ,Breast Neoplasms ,Article ,White People ,03 medical and health sciences ,0302 clinical medicine ,Breast cancer ,Risk Factors ,Medicine ,Humans ,Prospective Studies ,Risk factor ,education ,Prospective cohort study ,Gynecology ,education.field_of_study ,business.industry ,Obstetrics ,Age Factors ,Cancer ,General Medicine ,Odds ratio ,Middle Aged ,medicine.disease ,Black or African American ,030220 oncology & carcinogenesis ,Female ,business ,Sleep ,Body mass index ,030217 neurology & neurosurgery ,Cohort study - Abstract
Sleep has been suggested to influence breast cancer risk; however, the evidence is mixed. Black women have a higher prevalence of both short (6 h) and long (≥9 h) sleep duration and are more likely to develop more aggressive, hormone receptor-negative breast cancer. No study has examined the relationship between sleep and breast cancer in blacks. We focused on race-specific associations among the blacks.In the Southern Community Cohort Study (SCCS), a prospective study of which two-thirds of the population were black, we prospectively investigated self-reported sleep duration in relation to overall breast cancer risk by estrogen (ER) and progesterone receptor (PR) status in all women and in black women alone.Sleep duration was not associated with risk of total or hormone receptor-positive breast cancer. However, we found an inverse relationship between sleep duration and risk of ER- and PR- breast cancer among all women and in black women alone. Compared to the reference group (8 h), black women who reported shorter sleep duration had an increased risk of ER- PR- breast cancer (odds ratios; ORs (95% confidence intervals; CIs): 2.13 (1.15, 3.93), 1.66 (0.92, 3.02), and 2.22 (1.19, 4.12) for6, 6, and 7 h, respectively, (p for trend, 0.04).Short sleep duration may be a risk factor for hormone receptor-negative breast cancer among black women.
- Published
- 2015
39. Obesity, Physical Activity and Lower Urinary Tract Symptoms: Results From the Southern Community Cohort Study
- Author
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William J. Blot, David F. Penson, Jay H. Fowke, Lisa B. Signorello, and Heather M. Munro
- Subjects
Adult ,Male ,medicine.medical_specialty ,Urology ,Motor Activity ,Severity of Illness Index ,White People ,Article ,Metabolic equivalent ,Cohort Studies ,Prostate cancer ,Lower Urinary Tract Symptoms ,Lower urinary tract symptoms ,Internal medicine ,Severity of illness ,medicine ,Humans ,Obesity ,Prospective Studies ,Prospective cohort study ,Aged ,business.industry ,Middle Aged ,medicine.disease ,Black or African American ,Physical therapy ,International Prostate Symptom Score ,business ,Body mass index ,Follow-Up Studies ,Cohort study - Abstract
Obesity and physical activity have been posited as modifiable risk factors to delay lower urinary tract symptom progression. In this study we determined the independent associations of physical activity and obesity with lower urinary tract symptoms at followup among white and African-American men.Male participants 40 to 79 years old were identified from the Southern Community Cohort Study, a prospective cohort based in the southeastern United States. Baseline data collection included a validated physical activity questionnaire, height and weight, health history and other information. We excluded participants with a history of or medication use for benign prostatic hyperplasia or prostate cancer. Participants (7,318, 60% African-American) completed the International Prostate Symptom Score approximately 5 years after baseline. Patients with an International Prostate Symptom Score greater than 8 or 20 were classified as having moderate or severe lower urinary tract symptoms, respectively, at followup. Multivariable logistic regression was used to assess the relationships among obesity, physical activity and lower urinary tract symptoms.Moderate to severe lower urinary tract symptom severity at followup was significantly associated with a body mass index of 35 kg/m(2) or more (OR 1.38, 95% CI 1.17-1.63). Similarly the lowest categories of physical activity were associated with the onset of severe lower urinary tract symptoms in men with a normal body mass index (OR 1.38, 95% CI 1.05-1.82). These associations were independent of race.Severe obesity is associated with an increased risk of lower urinary tract symptoms at followup, while physical inactivity may permit progression of lower urinary tract symptoms in normal weight men regardless of race. These variables should be considered in future research into modifiable risk factors for lower urinary tract symptoms.
- Published
- 2011
40. HTR1B, ADIPOR1, PPARGC1A, and CYP19A1 and Obesity in a Cohort of Caucasians and African Americans: An Evaluation of Gene-Environment Interactions and Candidate Genes
- Author
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Jirong Long, William J. Blot, Sarah S. Cohen, Charles E. Matthews, Todd L. Edwards, Scott M. Williams, Digna R. Velez Edwards, David G. Schlundt, Lisa B. Signorello, Margaret K. Hargreaves, Xiao-Ou Shu, Qiuyin Cai, Wei Zheng, Jay H. Fowke, Raquel Villegas, Maciej S. Buchowski, and Smith Jeffrey
- Subjects
Male ,Candidate gene ,Alcohol Drinking ,Epidemiology ,Original Contributions ,Single-nucleotide polymorphism ,Motor Activity ,Overweight ,Polymorphism, Single Nucleotide ,White People ,Body Mass Index ,Aromatase ,Risk Factors ,Humans ,Medicine ,SNP ,Obesity ,Prospective Studies ,Genetic Association Studies ,Heat-Shock Proteins ,business.industry ,Smoking ,Middle Aged ,medicine.disease ,Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha ,Black or African American ,Cohort ,Linear Models ,Receptor, Serotonin, 5-HT1B ,Female ,Gene-Environment Interaction ,Receptors, Adiponectin ,medicine.symptom ,Energy Intake ,business ,Body mass index ,Transcription Factors ,Cohort study ,Demography - Abstract
The World Health Organization estimates that the number of obese and overweight adults has increased to 1.6 billion, with concomitant increases in comorbidity. While genetic factors for obesity have been extensively studied in Caucasians, fewer studies have investigated genetic determinants of body mass index (BMI; weight (kg)/height (m)(2)) in African Americans. A total of 38 genes and 1,086 single nucleotide polymorphisms (SNPs) in African Americans (n = 1,173) and 897 SNPs in Caucasians (n = 1,165) were examined in the Southern Community Cohort Study (2002-2009) for associations with BMI and gene × environment interactions. A statistically significant association with BMI survived correction for multiple testing at rs4140535 (β = -0.04, 95% confidence interval: -0.06, -0.02; P = 5.76 × 10(-5)) in African Americans but not in Caucasians. Gene-environment interactions were observed with cigarette smoking and a SNP in ADIPOR1 in African Americans, as well as between a different SNP in ADIPOR1 and physical activity in Caucasians. A SNP in PPARGC1A interacted with alcohol consumption in African Americans, and a different SNP in PPARGC1A was nominally associated in Caucasians. A SNP in CYP19A1 interacted with dietary energy intake in African Americans, and another SNP in CYP191A had an independent association with BMI in Caucasians.
- Published
- 2011
41. Long-term non-cancer mortality in pediatric and young adult cancer survivors in Finland
- Author
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Debra L. Friedman, John D. Boice, Pinki K. Prasad, Lisa B. Signorello, and Eero Pukkala
- Subjects
Adult ,Male ,Pediatrics ,medicine.medical_specialty ,Adolescent ,Respiratory Tract Diseases ,Article ,Young Adult ,Cause of Death ,Neoplasms ,medicine ,Humans ,Survivors ,Mortality ,Respiratory system ,Young adult ,Child ,Finland ,business.industry ,Respiratory disease ,Infant, Newborn ,Infant ,Cancer ,Hematology ,medicine.disease ,Pediatric cancer ,Confidence interval ,Lymphoma ,Oncology ,Cardiovascular Diseases ,Child, Preschool ,Pediatrics, Perinatology and Child Health ,Cohort ,Female ,business - Abstract
Background Excess late mortality has been reported among pediatric cancer survivors, but there is a need to further establish risk profiles for non-cancer death and to examine cause-specific mortality among survivors of young adult cancers. Procedures In a nationwide record linkage study in Finland, we identified 9,245 5-year cancer survivors diagnosed before age 35 and treated between 1966 and 1999, and followed them for mortality endpoints from 1971 to 2008. Standardized mortality ratios (SMRs) and 95% confidence intervals (95% CIs) were calculated to compare the observed number of deaths with those expected in the general Finnish population. Primary endpoints included death from cardiovascular and respiratory diseases; death from malignant diseases was excluded. Results Non-malignant disease mortality in the cohort was 90% higher (SMR = 1.9, 95% CI: 1.7–2.2) than expected, with SMRs for circulatory and respiratory disease similarly elevated (SMR = 1.9, 95% CI: 1.5–2.3 and SMR = 2.3, 95% CI: 1.3–3.8, respectively). Important differences were noted amongst patient subgroups, with risk greatest for survivors of central nervous system (CNS) cancer, Hodgkin lymphoma (HL), and non-Hodgkin lymphoma (NHL). The SMR's for circulatory disease were 6.6 (95% CI: 4.8–8.9) for HL and 4.8 (95% CI: 2.6–8.1) for NHL for the entire population; but these risks remained elevated for survivors diagnosed between 15 and 34 years of age. Conclusions Previous studies have shown that there is an elevated risk of non-cancer mortality in childhood cancer survivors; this is one of the first studies that show an increase in cardiovascular and respiratory mortality in long-term survivors of adolescent and young adult cancers. Pediatr Blood Cancer 2012; 58: 421–427. © 2011 Wiley Periodicals, Inc.
- Published
- 2011
42. Helicobacter pylori Prevalence and Circulating Micronutrient Levels in a Low-Income United States Population
- Author
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Pelayo Correa, Margaret K. Hargreaves, Jay H. Fowke, William J. Blot, Lisa B. Signorello, Meira Epplein, Angelika Michel, Qiuyin Cai, Michael Pawlita, and Wei Zheng
- Subjects
Adult ,Male ,Cancer Research ,Population ,Physiology ,Biology ,Article ,Helicobacter Infections ,Serology ,chemistry.chemical_compound ,Risk Factors ,Stomach Neoplasms ,Prevalence ,medicine ,Humans ,CagA ,Micronutrients ,education ,Poverty ,Aged ,education.field_of_study ,Helicobacter pylori ,Retinol ,Cancer ,Middle Aged ,Prognosis ,Micronutrient ,biology.organism_classification ,medicine.disease ,United States ,Oncology ,chemistry ,Immunology ,Female ,Cohort study - Abstract
High prevalence of Helicobacter pylori (H. pylori), the leading cause of gastric cancer, and low levels of micronutrients have been observed in many developing countries, and the question remains as to the whether an association between the 2 exists. The present study seeks to further our understanding of this potential connection in the Southern Community Cohort Study, representing a low-income population in the United States. Blood levels of antibodies to H. pylori proteins were assessed by multiplex serology for a sample of 310 African American and white participants, ages 40 to 79 years. Blood collected at baseline was also assayed for levels of carotenoids, tocopherols, retinol, and folate. Multivariate linear regression was used to calculate least-squares mean micronutrient levels within groups defined by H. pylori status. The mean serum levels of all micronutrients assayed were lower among H. pylori + individuals than H. pylori − individuals, significantly for β-carotene, folate, and retinol (decreases of 27.6%, 18.6%, and 9.7%, respectively). Individuals who were seropositive to the virulent CagA+ H. pylori strains had even lower mean levels of micronutrients, particularly β-carotene, folate, total carotenoids, and retinol (decreases of 38.9%, 19.1%, 17.0%, and 11.7%, respectively, compared with H. pylori − individuals). However, dietary micronutrient levels as derived from a food frequency questionnaire did not vary between groups defined by H. pylori status. These results provide support for the hypothesis that H. pylori infection impairs nutrient absorption and suggest a need for future studies to explore the role of H. pylori infection on nutrition and gastric cancer risk in this high-risk population. Cancer Prev Res; 4(6); 871–8. ©2011 AACR.
- Published
- 2011
43. Genome-wide association study of prostate cancer in men of African ancestry identifies a susceptibility locus at 17q21
- Author
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Iona Cheng, Stephen Watya, Anna M. Ray, Timothy R. Rebbeck, Kristine R. Monroe, John S. Witte, Sara S. Strom, Yuko Yamamura, John D. Carpten, Brian E. Henderson, Ann W. Hsing, Janet L. Stanford, Peggy Wan, M. Cristina Leske, Edder R. Duarte, Sonja I. Berndt, Loreall Pooler, William J. Blot, Charnita Zeigler-Johnson, Zhaoming Wang, Venetta Thomas, Stephen J. Chanock, David Van Den Berg, W. Ryan Diver, Richard B. Hayes, Michael J. Thun, Graham Casey, Benjamin A. Rybicki, Christopher A. Haiman, Sue A. Ingles, Bao Li Chang, Jennifer J. Hu, Kathleen A. Cooney, Qiuyin Cai, Barbara Nemesure, Loic Le Marchand, William B. Isaacs, Gary K. Chen, Jennifer Haslag-Minoff, Esther M. John, S. Lilly Zheng, Glenn O. Allen, Xin Sheng, Suh Yuh Wu, Laurence N. Kolonel, Erin N. Carter, Elaine A. Ostrander, Christine Neslund-Dudas, Suzanne Kolb, Lisa B. Signorello, Yao Tettey, Adam B. Murphy, Rick A. Kittles, Jianfeng Xu, Fredrick R. Schumacher, William Wu, Lucy Xia, Adam S. Kibel, Daniel O. Stram, Anselm Hennis, Edward D. Yeboah, and Serigne Magueye Gueye
- Subjects
Male ,Genome-wide association study ,Disease ,Biology ,Polymorphism, Single Nucleotide ,Article ,03 medical and health sciences ,Prostate cancer ,0302 clinical medicine ,Genetics ,medicine ,Humans ,Genetic Predisposition to Disease ,Allele ,030304 developmental biology ,Genetic association ,0303 health sciences ,Prostatic Neoplasms ,Chromosome ,Cancer ,Odds ratio ,medicine.disease ,3. Good health ,Black or African American ,030220 oncology & carcinogenesis ,Chromosomes, Human, Pair 17 ,Genome-Wide Association Study - Abstract
In search of common risk alleles for prostate cancer that could contribute to high rates of the disease in men of African ancestry, we conducted a genome-wide association study, with 1,047,986 SNP markers examined in 3,425 African-Americans with prostate cancer (cases) and 3,290 African-American male controls. We followed up the most significant 17 new associations from stage 1 in 1,844 cases and 3,269 controls of African ancestry. We identified a new risk variant on chromosome 17q21 (rs7210100, odds ratio per allele = 1.51, P = 3.4 × 10(-13)). The frequency of the risk allele is ∼5% in men of African descent, whereas it is rare in other populations (
- Published
- 2011
44. Cancer Mortality Among US Workers Employed in Semiconductor Wafer Fabrication
- Author
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Donald E. Marano, William J. Blot, Robert E. Tarone, Heather M. Munro, John D. Boice, Bandana Chadda, Lisa B. Signorello, and Joseph K. McLaughlin
- Subjects
Male ,medicine.medical_specialty ,Air Pollutants, Occupational ,Occupational safety and health ,Cohort Studies ,Occupational medicine ,Cause of Death ,Neoplasms ,Occupational Exposure ,Environmental health ,Epidemiology ,Humans ,Industry ,Medicine ,Registries ,Aged ,business.industry ,technology, industry, and agriculture ,Public Health, Environmental and Occupational Health ,Cancer ,Middle Aged ,medicine.disease ,United States ,Occupational Diseases ,Vital Statistics ,Semiconductors ,Relative risk ,Epidemiological Monitoring ,Cohort ,Female ,Semiconductor wafer fabrication ,business ,Environmental Monitoring ,Cohort study - Abstract
Objective: To evaluate potential cancer risks in the US semiconductor wafer fabrication industry. Methods: A cohort of 100,081 semiconductor workers employed between 1968 and 2002 was studied. Standardized mortality ratios and relative risks (RRs) were estimated. Results: Standardized mortality ratios were similar and significantly low among fabrication and nonfabrication workers for all causes (0.54 and 0.54) and all cancers (0.74 and 0.72). Internal comparisons also showed similar overall cancer risks among fabrication workers (RR = 0.98), including process equipment operators and process equipment service technicians (OP/EST) employed in cleanrooms (RR = 0.97), compared with nonfabrication workers. Nonsignificantly elevated RRs were observed for a few cancer sites among OP/EST workers, but the numbers of deaths were small and there were no trends of increasing risk with duration of employment. Conclusions: Work in the US semiconductor industry, including semiconductor wafer fabrication in cleanrooms, was not associated with increased cancer mortality overall or mortality from any specific form of cancer. However, due to the young average age of this cohort and its associated relatively low numbers of deaths, regular mortality updates of this semiconductor worker cohort are warranted.
- Published
- 2010
45. Blood Vitamin D Levels in Relation to Genetic Estimation of African Ancestry
- Author
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Jirong Long, Jeffrey R. Smith, William J. Blot, Margaret K. Hargreaves, Wei Zheng, Bruce W. Hollis, Lisa B. Signorello, Qiuyin Cai, and Scott M. Williams
- Subjects
Male ,Epidemiology ,Physiology ,Biology ,Article ,vitamin D deficiency ,Cohort Studies ,chemistry.chemical_compound ,Risk Factors ,Vitamin D and neurology ,medicine ,Humans ,Prospective Studies ,Vitamin D ,Prospective cohort study ,Genetics ,Vitamina d ,Middle Aged ,Vitamin D Deficiency ,medicine.disease ,Black or African American ,Oncology ,chemistry ,Genetic marker ,Female ,Cholecalciferol ,Cohort study - Abstract
Background: African-Americans generally have lower circulating levels of 25 hydroxyvitamin D [25(OH)D] than Whites, attributed to skin pigmentation and dietary habits. Little is known about the genetic determinants of 25(OH)D levels nor whether the degree of African ancestry associates with circulating 25(OH)D. Methods: With the use of a panel of 276 ancestry informative genetic markers, we estimated African and European admixture for a sample of 758 African-American and non-Hispanic White Southern Community Cohort Study participants. For African-Americans, cut points of Results: The mean serum 25(OH)D levels among Whites and among African-Americans of low, medium, and high African ancestry were 27.2, 19.5, 18.3, and 16.5 ng/mL, respectively. Serum 25(OH)D was estimated to decrease by 1.0 to 1.1 ng/mL per 10% increase in African ancestry. The effect of high vitamin D exposure from sunlight and diet was 46% lower among African-Americans with high African ancestry than among those with low/medium ancestry. Conclusions: We found novel evidence that the level of African ancestry may play a role in clinical vitamin D status. Impact: This is the first study to describe how 25(OH)D levels vary in relation to genetic estimation of African ancestry. Further study is warranted to replicate these findings and uncover the potential pathways involved. Cancer Epidemiol Biomarkers Prev; 19(9); 2325–31. ©2010 AACR.
- Published
- 2010
46. Obesity is associated with an increased risk of monoclonal gammopathy of undetermined significance among black and white women
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William J. Blot, Ola Landgren, Qiuyin Cai, Ruth M. Pfeiffer, Jerry A. Katzmann, Lisa B. Signorello, S. Vincent Rajkumar, Angela Dispenzieri, Joseph F. Fraumeni, Lynn R. Goldin, Neil E. Caporaso, and Robert A. Kyle
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Adult ,Oncology ,medicine.medical_specialty ,Immunology ,Black People ,Monoclonal Gammopathy of Undetermined Significance ,Biochemistry ,White People ,Risk Factors ,immune system diseases ,hemic and lymphatic diseases ,Internal medicine ,medicine ,Genetic predisposition ,Humans ,Obesity ,cardiovascular diseases ,Risk factor ,Multiple myeloma ,Aged ,Retrospective Studies ,business.industry ,Age Factors ,Absolute risk reduction ,Cell Biology ,Hematology ,Odds ratio ,Middle Aged ,medicine.disease ,Survival Rate ,Treatment Outcome ,Female ,Multiple Myeloma ,business ,Monoclonal gammopathy of undetermined significance ,Negroid - Abstract
Obesity and black race have been associated with excess risk of multiple myeloma. The association of obesity with monoclonal gammopathy of undetermined significance (MGUS) is unknown. Further, it is not known whether the increased risk of multiple myeloma and MGUS in blacks is related to socioeconomic status, genetic susceptibility, or both. We screened 1000 black and 996 white women (range, 40-79 years) of similar socioeconomic status for MGUS; the aim of the study was to assess MGUS risk in relation to obesity and race. A total of 39 (3.9%) blacks and 21 (2.1%) whites had MGUS. On multivariate analysis, obesity (odds ratio [OR] = 1.8; P = .04), black race (OR = 1.8; P = .04), and increasing age (> 55 vs < 43 years; OR = 2.5; P = .03) were independently associated with an excess risk of MGUS. Our findings support the hypothesis that obesity is etiologically linked to myelomagenesis. The 2-fold excess of MGUS among blacks compared with whites of similar socioeconomic status supports a role for susceptibility genes in MGUS.
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- 2010
47. Stillbirth and neonatal death in relation to radiation exposure before conception: a retrospective cohort study
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Ann C. Mertens, Heather M. Munro, Daniel M. Green, Leslie L. Robison, Lisa B. Signorello, John J. Mulvihill, John Whitton, Rita E. Weathers, Marilyn Stovall, and John D. Boice
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Male ,medicine.medical_specialty ,Offspring ,Pregnancy ,Uterine cancer ,Neoplasms ,Infant Mortality ,Testis ,medicine ,Humans ,Survivors ,Testicular cancer ,Gynecology ,business.industry ,Ovary ,Uterus ,Infant, Newborn ,Cancer ,Radiotherapy Dosage ,Retrospective cohort study ,General Medicine ,Stillbirth ,medicine.disease ,Maternal Exposure ,Fertilization ,Relative risk ,Female ,business ,Cohort study - Abstract
Summary Background The reproductive implications of mutagenic treatments given to children with cancer are not clear. By studying the risk of untoward pregnancy outcomes, we indirectly assessed the risk of transmission of germline damage to the offspring of survivors of childhood cancer who were given radiotherapy and chemotherapy. Methods We did a retrospective cohort analysis, within the Childhood Cancer Survivor Study (CCSS), of the risk of stillbirth and neonatal death among the offspring of men and women who had survived childhood cancer. Patients in CCSS were younger than 21 years at initial diagnosis of an eligible cancer, were treated at 25 US institutions and one Canadian institution, and had survived for at least 5 years after diagnosis. We quantified the chemotherapy given to patients, and the preconception radiation doses to the testes, ovaries, uterus, and pituitary gland, and related these to the risk of stillbirth or neonatal death using Poisson regression analysis. Findings Among 1148 men and 1657 women who had survived childhood cancer, there were 4946 pregnancies. Irradiation of the testes (16 [1%] of 1270; adjusted relative risk 0·8 [95% CI 0·4–1·6]; mean dose 0·53 Gy [SD 1·40]) and pituitary gland (17 [3%] of 510, 1·1 [0·5–2·4] for more than 20·00 Gy; mean dose 10·20 Gy [13·0] for women), and chemotherapy with alkylating drugs (26 [2%] of 1195 women, 0·9 [0·5–1·5]; ten [1%] of 732 men, 1·2 [0·5–2·5]) were not associated with an increased risk of stillbirth or neonatal death. Uterine and ovarian irradiation significantly increased risk of stillbirth and neonatal death at doses greater than 10·00 Gy (five [18%] of 28, 9·1 [3·4–24·6]). For girls treated before menarche, irradiation of the uterus and ovaries at doses as low as 1·00–2·49 Gy significantly increased the risk of stillbirth or neonatal death (three [4%] of 69, 4·7 [1·2–19·0]). Interpretation Our findings do not support concern about heritable genetic changes affecting the risk of stillbirth and neonatal death in the offspring of men exposed to gonadal irradiation. However, uterine and ovarian irradiation had serious adverse effects on the offspring that were probably related to uterine damage. Careful management is warranted of pregnancies in women given high doses of pelvic irradiation before puberty. Funding Westlakes Research Institute, National Cancer Institute, and Children's Cancer Research Fund.
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- 2010
48. Abstract B28: Baseline prostate-specific antigen (PSA) levels in midlife predict aggressive prostate cancer in African-American men
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Sarah C. Markt, Travis Gerke, Kathryn M. Wilson, Sigrid Carlsson, Mark Steinwandel, Lorelei A. Mucci, Adam S. Kibel, William J. Blot, Andrew J. Vickers, Daniel Sjöberg, Quoc-Dien Trinh, Lisa B. Signorello, Hans Lilja, and Mark A. Preston
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Oncology ,Cancer Research ,medicine.medical_specialty ,business.industry ,Incidence (epidemiology) ,Cancer ,Odds ratio ,medicine.disease ,Confidence interval ,Prostate cancer ,Prostate-specific antigen ,Internal medicine ,Relative risk ,medicine ,business ,Cohort study - Abstract
Background: Baseline prostate specific antigen (PSA) levels measured in midlife predict future prostate cancer mortality among white men. There are minimal data on whether a baseline PSA in African-American men, who experience the highest incidence and mortality of this disease, predicts future aggressive prostate cancer. Methods: We undertook a nested case-control study among African-American men age 40 to 64 years who gave prediagnostic blood at enrollment in the Southern Community Cohort Study between 2002-2009 and were followed a median of 9 years for cancer incidence and mortality through 2015. Baseline total and free PSA levels were available for 197 prostate cancer cases (55 aggressive cases, Gleason ≥4+3=7, AJCC Stage III or IV, or cancer-specific death) and 569 age-matched controls. Conditional logistic regression was used to estimate odds ratios (ORs) with 95% confidence intervals (CIs) for the association between baseline PSA levels and risk of total and aggressive prostate cancer. Results: Median PSA among controls was 0.72, 0.80, 0.94, and 1.03 ng/mL for men aged 40 to 49, 50 to 54, 55 to 59, and 60 to 64 years, respectively. Relative risk of total prostate cancer was strongly associated with baseline PSA levels in midlife: ORs (95% CIs) comparing PSA levels in the >90th percentile vs. ≤median were 93.7 (22.5-390) at 40 to 54 years and 77.0 (24.9-238) at 55 to 64 years. Risk of aggressive prostate cancer was also strongly associated with baseline PSA levels in midlife: ORs (95% CIs) comparing PSA levels in the >90th percentile vs. ≤median were 80.8 (14.7 to infinity) at 40-54 years Citation Format: Mark Preston, Travis Gerke, Sigrid V. Carlsson, Lisa Signorello, Daniel D. Sjoberg, Sarah C. Markt, Adam S. Kibel, Quoc-Dien Trinh, Mark Steinwandel, William Blot, Andrew J. Vickers, Hans Lilja, Lorelei A. Mucci, Kathryn M. Wilson. Baseline prostate-specific antigen (PSA) levels in midlife predict aggressive prostate cancer in African-American men [abstract]. In: Proceedings of the AACR International Conference: New Frontiers in Cancer Research; 2017 Jan 18-22; Cape Town, South Africa. Philadelphia (PA): AACR; Cancer Res 2017;77(22 Suppl):Abstract nr B28.
- Published
- 2017
49. Race and Socioeconomic Status are Independently Associated With Benign Prostatic Hyperplasia
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Jay H. Fowke, Harvey J. Murff, William J. Blot, Lars Lund, and Lisa B. Signorello
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Adult ,Male ,medicine.medical_specialty ,National Health and Nutrition Examination Survey ,Cross-sectional study ,Urology ,Population ,Prostatic Hyperplasia ,Severity of Illness Index ,Article ,White People ,Age Distribution ,Risk Factors ,Lower urinary tract symptoms ,Surveys and Questionnaires ,Internal medicine ,Confidence Intervals ,Odds Ratio ,Prevalence ,medicine ,Humans ,education ,Socioeconomic status ,Aged ,Aged, 80 and over ,Gynecology ,education.field_of_study ,business.industry ,Transurethral Resection of Prostate ,Middle Aged ,Hyperplasia ,medicine.disease ,United States ,Black or African American ,Prostate-specific antigen ,Cross-Sectional Studies ,Logistic Models ,Socioeconomic Factors ,Multivariate Analysis ,Marital status ,business ,Attitude to Health - Abstract
Prostate enlargement is common as men age. However, differences in the diagnosis or treatment of clinical benign prostatic hyperplasia between black and white men remain poorly understood. We investigated racial differences in and surgical intervention for benign prostatic hyperplasia in a large and predominantly low income population.Participants included 21,949 men, of whom 79.8% were black and 20.2% were white, recruited from 60 community health centers in the southeastern United States between 2002 and 2007. Benign prostatic hyperplasia, surgical intervention for benign prostatic hyperplasia, and economic and demographic indexes, eg education, household income, health insurance and marital status, were determined by an interview in person. Logistic regression was used to summarize the association between race and benign prostatic hyperplasia while controlling for health care access and socioeconomic status.Black men were approximately half as likely to report a benign prostatic hyperplasia diagnosis compared to white men (4.1% vs 9.9%, age adjusted OR 0.45, 95% CI 0.40, 0.51), a difference that persisted with only small abatement after controlling for age, income, insurance coverage, comorbidity, education and other factors (adjusted OR 0.49, 95% CI 0.43, 0.56)). Of men with benign prostatic hyperplasia surgical intervention for that condition (133 patients) was more prevalent in black vs white men (12.9% vs 9.1%, adjusted OR 1.65, 95% CI 1.10, 2.48).After controlling for economic factors associated with benign prostatic hyperplasia black men were significantly less likely to report a prior benign prostatic hyperplasia diagnosis. In contrast, surgical intervention typically reserved for severe benign prostatic hyperplasia was more common in black men. Our results suggest that race and socioeconomic status are independently associated with benign prostatic hyperplasia.
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- 2008
50. Comparing Diabetes Prevalence Between African Americans and Whites of Similar Socioeconomic Status
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Sarah S. Cohen, Lisa B. Signorello, William J. Blot, Maciej S. Buchowski, Margaret K. Hargreaves, Joseph K. McLaughlin, David G. Schlundt, and Mark Steinwandel
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Adult ,Male ,Diabetes risk ,Research and Practice ,Ethnic origin ,Type 2 diabetes ,White People ,Body Mass Index ,Risk Factors ,Prevalence ,medicine ,Humans ,Sex Distribution ,Risk factor ,Socioeconomic status ,Aged ,business.industry ,Public Health, Environmental and Occupational Health ,Health Status Disparities ,Odds ratio ,Middle Aged ,medicine.disease ,Southeastern United States ,Black or African American ,Logistic Models ,Diabetes Mellitus, Type 2 ,Social Class ,Multivariate Analysis ,Female ,business ,Body mass index ,Cohort study ,Demography - Abstract
Objectives. We investigated whether racial disparities in the prevalence of type 2 diabetes exist beyond what may be attributable to differences in socioeconomic status (SES) and other modifiable risk factors. Methods. We analyzed data from 34331 African American and 9491 White adults aged 40 to 79 years recruited into the ongoing Southern Community Cohort Study. Participants were enrolled at community health centers and had similar socioeconomic circumstances and risk factor profiles. We used logistic regression to estimate the association between race and prevalence of self-reported diabetes after taking into account age, SES, health insurance coverage, body mass index, physical activity, and hypertension. Results. Multivariate analyses accounting for several diabetes risk factors did not provide strong support for higher diabetes prevalence rates among African Americans than among Whites (men: odds ratio [OR]=1.07; 95% confidence interval [CI]=0.95, 1.20); women: OR=1.13, 95% CI=1.04, 1.22). Conclusions. Our findings suggest that major differences in diabetes prevalence between African Americans and Whites may simply reflect differences in established risk factors for the disease, such as SES, that typically vary according to race.
- Published
- 2007
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