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Background: Inflammation is pivotal to the progression of atherosclerosis. Cholesterol crystals (CCs) that grow and enlarge within the plaque core can cause plaque rupture and trigger inflammation as they deposit into the atherosclerotic bed. Thus, agents that affect CC formation, expansion, and morphology may reduce cardiovascular (CV) risk independent of lipid-lowering and anti-inflammatory therapy. Objective: Because colchicine is highly concentrated in leukocytes that can enter the atherosclerotic plaque core, we tested its effect on the formation and growth of CCs in bench experiments to determine whether it may have direct effects on CCs, independent of its known anti-inflammatory actions. Method: Different dosages of colchicine mixed with cholesterol (0.05-5â mg/ml/g of cholesterol) were used to influence the formation CCs and volume expansion in vitro. These were compared to control samples with cholesterol in ddH2O without colchicine. In an ex vivo study, fresh atherosclerotic human plaques were incubated with and without colchicine in a water bath at 37°C for 48â h to assess the impact of colchicine on CC morphology. Scanning electron microscopy (SEM) was utilized to analyze CC morphology in samples from the various treatment groups. Results: The addition of colchicine to cholesterol caused a substantial dose-dependent reduction in volume (p < 0.05). Pairwise comparisons of volume reduction, showed a significant reduction in volume at 5â mg/ml/g when compared to control (p < 0.02) but the calculated Cohen's d effect size was large for five of the six pairwise comparisons. By SEM, CCs from both in vitro and ex vivo samples treated with colchicine had evidence of dissolution and changes in their morphology as evidenced by the loss of their sharp edges. In contrast, CCs in untreated specimens retained their typical geometric structure. Conclusions: Colchicine can reduce CC formation and expansion and alter CC morphology. These previously unappreciated effects of colchicine may contribute to its clinical benefit in patients with CV disease independent of its anti-inflammatory effects.
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PURPOSE: The role of alcohol in young-onset breast cancer (YOBC) is unclear. We examined associations between lifetime alcohol consumption and YOBC in the Young Women's Health History Study, a population-based case-control study of breast cancer among Non-Hispanic Black and White women < 50 years of age. METHODS: Breast cancer cases (n = 1,812) were diagnosed in the Metropolitan Detroit and Los Angeles County SEER registry areas, 2010-2015. Controls (n = 1,381) were identified through area-based sampling and were frequency-matched to cases by age, site, and race. Alcohol consumption and covariates were collected from in-person interviews. Weighted multivariable logistic regression was conducted to calculate adjusted odds ratios (aOR) and 95% confidence intervals (CI) for associations between alcohol consumption and YOBC overall and by subtype (Luminal A, Luminal B, HER2, or triple negative). RESULTS: Lifetime alcohol consumption was not associated with YOBC overall or with subtypes (all ptrend ≥ 0.13). Similarly, alcohol consumption in adolescence, young and middle adulthood was not associated with YOBC (all ptrend ≥ 0.09). An inverse association with triple-negative YOBC, however, was observed for younger age at alcohol use initiation (< 18 years vs. no consumption), aOR (95% CI) = 0.62 (0.42, 0.93). No evidence of statistical interaction by race or household poverty was observed. CONCLUSIONS: Our findings suggest alcohol consumption has a different association with YOBC than postmenopausal breast cancer-lifetime consumption was not linked to increased risk and younger age at alcohol use initiation was associated with a decreased risk of triple-negative YOBC. Future studies on alcohol consumption in YOBC subtypes are warranted.
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Consumo de Bebidas Alcohólicas , Neoplasias de la Mama , Neoplasias de la Mama Triple Negativas , Femenino , Humanos , Consumo de Bebidas Alcohólicas/epidemiología , Consumo de Bebidas Alcohólicas/efectos adversos , Neoplasias de la Mama/epidemiología , Neoplasias de la Mama/etiología , Estudios de Casos y Controles , Receptor ErbB-2 , Receptores de Progesterona , Factores de Riesgo , Neoplasias de la Mama Triple Negativas/epidemiología , Neoplasias de la Mama Triple Negativas/etiología , Negro o Afroamericano , Blanco , Edad de InicioRESUMEN
Background and aims: Cancer and atherosclerosis share common risk factors and inflammatory pathways that promote their proliferation via vascular endothelial growth factor (VEGF). Because CCs cause mechanical injury and inflammation in atherosclerosis, we investigated their presence in solid cancers and their activation of IL-1ß, VEGF, CD44, and Ubiquityl-Histone H2B (Ub-H2B), that promote cancer growth. Methods: Tumor specimens from eleven different types of human cancers and atherosclerotic plaques were assessed for CCs, free cholesterol content and IL1-ß by microscopy, immunohistochemistry, and biochemical analysis. Breast and colon cancer cell lines were cultured with and without CCs to select for expression of VEGF, CD44, and Ub-H2B. Western blot and immunofluorescence were performed on cells to assess the effect of CCs on signaling pathways. Results: Cancers displayed higher CC content (+2.29 ± 0.74 vs +1.46 ± 0.84, p < 0.0001), distribution (5.06 ± 3.13 vs 2.86 ± 2.18, p < 0.001) and free cholesterol (3.63 ± 4.02 vs 1.52 ± 0.56 µg/mg, p < 0.01) than cancer free marginal tissues and similarly for atherosclerotic plaques and margins (+2.31 ± 0.51 vs +1.44 ± 0.79, p < 0.02; 14.0 ± 5.74 vs 8.14 ± 5.52, p < 0.03; 0.19 ± 0.14 vs 0.09 ± 0.04 µg/mg, p < 0.02) respectively. Cancers displayed significantly increased expression of IL1-ß compared to marginal tissues. CCs treated cancer cells had increased expression of VEGF, CD44, and Ub-H2B compared to control. By microscopy, CCs were found perforating cancer tumors similar to plaque rupture. Conclusions: These findings suggest that CCs can induce trauma and activate cytokines that enhance cancer growth as in atherosclerosis.
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PURPOSE: To evaluate the association between lifetime personal cigarette smoking and young-onset breast cancer (YOBC; diagnosed <50 years of age) risk overall and by breast cancer (BC) subtype, and whether risk varies by race or socioeconomic position (SEP). METHODS: Data are from the Young Women's Health History Study (YWHHS), a population-based case-control study of non-Hispanic Black (NHB) and White (NHW) women, ages 20-49 years (n = 1812 cases, n = 1381 controls) in the Los Angeles County and Metropolitan Detroit Surveillance, Epidemiology, and End Results (SEER) registry areas, 2010-2015. Lifetime personal cigarette smoking characteristics and YOBC risk by subtype were examined using sample-weighted, multivariable-adjusted polytomous logistic regression. RESULTS: YOBC risk associated with ever versus never smoking differed by subtype (Pheterogeneity = 0.01) with risk significantly increased for Luminal A (adjusted odds ratio [aOR] 1.34; 95% confidence interval [CI] 1.06-1.68) and HER2-type (aOR 1.97; 95% CI 1.23-3.16), and no association with Luminal B or Triple Negative subtypes. Additionally, ≥30 years since smoking initiation (versus never) was statistically significantly associated with an increased risk of Luminal A (aOR 1.55; 95% CI 1.07-2.26) and HER2-type YOBC (aOR 2.77; 95% CI 1.32-5.79), but not other subtypes. In addition, among parous women, smoking initiated before first full-term pregnancy (versus never) was significantly associated with an increased risk of Luminal A YOBC (aOR 1.45; 95% CI 1.11-1.89). We observed little evidence for interactions by race and SEP. CONCLUSION: Findings confirm prior reports of a positive association between cigarette smoking and Luminal A YOBC and identify a novel association between smoking and HER2-type YOBC.
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Neoplasias de la Mama , Fumar Cigarrillos , Adulto , Neoplasias de la Mama/epidemiología , Neoplasias de la Mama/etiología , Estudios de Casos y Controles , Fumar Cigarrillos/efectos adversos , Fumar Cigarrillos/epidemiología , Femenino , Humanos , Persona de Mediana Edad , Embarazo , Receptor ErbB-2 , Receptores de Estrógenos , Receptores de Progesterona , Factores de Riesgo , Adulto JovenRESUMEN
Lack of consistency in the relationship between dairy products consumption and breast cancer (BC) risk motivated us to evaluate this association in a case-control study of BC among Polish women. The study includes 1699 women 26-79 years of age, 823 BC cases identified in Cancer Registries and 876 randomly selected controls from the national population registry. Using a validated, semiquantitative food frequency questionnaire (FFQ), the consumption of dairy products was collected for a time period of 10-15 years prior to BC diagnosis. We used logistic regression, adjusting for potential confounders, to assess the relationship between total dairy consumption as well as individual dairy groups of milk, cottage cheese and hard cheese and BC risk for premenopausal and postmenopausal women. For total consumption, a significant decrease in BC risk was observed with increased consumption of one serving/week, OR trend = 0.98, 2% decrease in risk, for premenopausal women only. For milk, a significant decrease in BC risk was observed for an increase in consumption of one glass/week, OR trend = 0.95, 5% decrease, in both strata of menopause. In contrast, for hard cheese, a significant increase in the risk of 10% was observed only in premenopausal women, OR trend = 1.10. Cottage cheese consumption significantly reduced BC risk by 20%, OR trend = 0.80, for an increase in one serving/week for postmenopausal women only. Our results show that individual dairy products have a statistically significant but bi-directional relationship with BC risk, which differs for premenopausal and postmenopausal women.
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Neoplasias de la Mama/epidemiología , Neoplasias de la Mama/etiología , Productos Lácteos/estadística & datos numéricos , Dieta/estadística & datos numéricos , Adulto , Anciano , Animales , Estudios de Casos y Controles , Queso/estadística & datos numéricos , Encuestas sobre Dietas , Femenino , Humanos , Incidencia , Modelos Logísticos , Persona de Mediana Edad , Leche/estadística & datos numéricos , Polonia/epidemiología , Sistema de Registros , Factores de RiesgoRESUMEN
PURPOSE: The etiology of young-onset breast cancer (BC) is poorly understood, despite its greater likelihood of being hormone receptor-negative with a worse prognosis and persistent racial and socioeconomic inequities. We conducted a population-based case-control study of BC among young Black and White women and here discuss the theory that informed our study, exposures collected, study methods, and operational results. METHODS: Cases were non-Hispanic Black (NHB) and White (NHW) women age 20-49 years with invasive BC in metropolitan Detroit and Los Angeles County SEER registries 2010-2015. Controls were identified through area-based sampling from the U.S. census and frequency matched to cases on study site, race, and age. An eco-social theory of health informed life-course exposures collected from in-person interviews, including socioeconomic, reproductive, and energy balance factors. Measured anthropometry, blood (or saliva), and among cases SEER tumor characteristics and tumor tissue (from a subset of cases) were also collected. RESULTS: Of 5,309 identified potentially eligible cases, 2,720 sampled participants were screened and 1,812 completed interviews (682 NHB, 1140 NHW; response rate (RR): 60%). Of 24,612 sampled control households 18,612 were rostered, 2,716 participants were sampled and screened, and 1,381 completed interviews (665 NHB, 716 NHW; RR: 53%). Ninety-nine% of participants completed the main interview, 82% provided blood or saliva (75% blood only), and SEER tumor characteristics (including ER, PR and HER2 status) were obtained from 96% of cases. CONCLUSIONS: Results from the successfully established YWHHS should expand our understanding of young-onset BC etiology overall and by tumor type and identify sources of racial and socioeconomic inequities in BC.
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Neoplasias de la Mama , Adulto , Negro o Afroamericano , Neoplasias de la Mama/epidemiología , Estudios de Casos y Controles , Femenino , Humanos , Incidencia , Persona de Mediana Edad , Población Blanca , Adulto JovenRESUMEN
Breast cancer is the leading cause of cancer-related disease in women. Cumulative evidence supports a causal role of alcohol intake and breast cancer incidence. In this study, we explore the change on expression of genes involved in the biological pathways through which alcohol has been hypothesized to impact breast cancer risk, to shed new insights on possible mechanisms affecting the survival of breast cancer patients. Here, we performed differential expression analysis at individual genes and gene set levels, respectively, across survival and breast cancer subtype data. Information about postdiagnosis breast cancer survival was obtained from 1977 Caucasian female participants in the Molecular Taxonomy of Breast Cancer International Consortium. Expression of 16 genes that have been linked in the literature to the hypothesized alcohol-breast cancer pathways, were examined. We found that the expression of 9 out of 16 genes under study were associated with cancer survival within the first 4 years of diagnosis. Results from gene set analysis confirmed a significant differential expression of these genes as a whole too. Although alcohol consumption is not analyzed, nor available for this dataset, we believe that further study on these genes could provide important information for clinical recommendations about potential impact of alcohol drinking on breast cancer survival.
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Consumo de Bebidas Alcohólicas/genética , Neoplasias de la Mama/genética , Regulación Neoplásica de la Expresión Génica/genética , Adulto , Anciano , Consumo de Bebidas Alcohólicas/epidemiología , Consumo de Bebidas Alcohólicas/mortalidad , Mama/patología , Neoplasias de la Mama/diagnóstico , Neoplasias de la Mama/mortalidad , Etanol , Femenino , Humanos , Incidencia , Persona de Mediana Edad , Medición de Riesgo/métodos , Factores de RiesgoRESUMEN
OBJECTIVE: To evaluate interaction of HLA-DPß1 and DRß1 polymorphisms with metrics of beryllium exposure, in the development of beryllium sensitization (BeS) and chronic beryllium disease (CBD). METHODS: A matched case-control study of 61 CBD, 41 BeS, and 259 controls from two beryllium-processing facilities. RESULTS: BES and CBD were significantly associated with presence of DPßE69. Dose response of exposure was not observed for the development of BES and CBD with/without adjustment for DPßE69 (Pâ>â0.05). The DRßE71 polymorphism was more common in BeS than CBD after adjusting for exposure and maybe a protective factor (aOR 0.4, 95% CI 0.2 to 0.9) against the progression of BeS to CBD. CONCLUSION: No exposure-response association was found, which may reflect that the workers in this high exposure cohort were above a threshold level where an exposure-response could be observed.
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Beriliosis/genética , Berilio/toxicidad , Exposición Profesional/estadística & datos numéricos , Estudios de Casos y Controles , Estudios de Cohortes , Cadenas beta de HLA-DP/genética , Humanos , Proteínas del Tejido Nervioso/genética , Polimorfismo Genético , Proteínas de Unión al ARN/genéticaRESUMEN
Cholesterol crystals (CCs) have been associated with plaque rupture through mechanical injury and inflammation. This study evaluated the presence of CCs during acute myocardial infarction (AMI) and associated myocardial injury, inflammation, and arterial blood flow before and after percutaneous coronary intervention. Patients presenting with AMI (n = 286) had aspiration of culprit coronary artery obstruction. Aspirates were evaluated for crystal content, size, composition, and morphology by scanning electron microscopy, crystallography, and infrared spectroscopy. These were correlated with inflammatory biomarkers, cardiac enzymes, % coronary stenosis, and Thrombolysis in Myocardial Infarction (TIMI) blush and flow grades. Crystals were detected in 254 patients (89%) and confirmed to be cholesterol by spectroscopy. Of 286 patients 240 (84%) had CCs compacted into clusters that were large enough to be measured and analyzed. Moderate to extensive CC content was present in 172 cases (60%). Totally occluded arteries had significantly larger CC clusters than partially occluded arteries (p <0.05). Patients with CC cluster area >12,000 µm2 had significantly elevated interleukin-1 beta (IL-1ß) levels (p <0.01), were less likely to have TIMI blush grade of 3 (p <0.01), and more likely to have TIMI flow grade of 1 (p <0.01). Patients with recurrent AMI had smaller CC cluster area (p <0.04), lower troponin (p <0.02), and IL-1ß levels (p <0.04). Women had smaller CC clusters (p <0.04). Macrophages in the aspirates were found to be attached to CCs. Coronary artery aspirates had extensive deposits of CCs during AMI. In conclusion, presence of large CC clusters was associated with increased inflammation (IL-1ß), increased arterial narrowing, and diminished reflow following percutaneous coronary intervention.
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Colesterol/metabolismo , Oclusión Coronaria/complicaciones , Vasos Coronarios/metabolismo , Inflamación/metabolismo , Infarto del Miocardio/complicaciones , Intervención Coronaria Percutánea , Placa Aterosclerótica/metabolismo , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Proteína C-Reactiva/metabolismo , Angiografía Coronaria , Circulación Coronaria/fisiología , Oclusión Coronaria/diagnóstico , Oclusión Coronaria/metabolismo , Vasos Coronarios/diagnóstico por imagen , Vasos Coronarios/fisiopatología , Citocinas/metabolismo , Ensayo de Inmunoadsorción Enzimática , Femenino , Estudios de Seguimiento , Humanos , Incidencia , Inflamación/diagnóstico , Masculino , Persona de Mediana Edad , Infarto del Miocardio/metabolismo , Infarto del Miocardio/cirugía , Placa Aterosclerótica/complicaciones , Placa Aterosclerótica/epidemiología , Estudios Retrospectivos , Factores de Riesgo , Análisis Espectral , Estados Unidos/epidemiología , Adulto JovenRESUMEN
RATIONALE & OBJECTIVES: We sought to develop an abbreviated protocol (AP) for breast MRI that maximizes lesion detection by assessing each lesion not seen on mammography by each acquisition from a full diagnostic protocol (FDP). MATERIALS & METHODS: 671 asymptomatic women (mean 55.7 years, range 40-80) with a negative mammogram were prospectively enrolled in this IRB approved study. All lesions on MRI not visualized on mammography were analyzed, reported, and suspicious lesions biopsied. In parallel, all FDP MRI acquisitions were scored by lesion to eventually create a high-yield AP. RESULTS: FDP breast MRI detected 452 findings not visible on mammography, including 17 suspicious lesions recommended for biopsy of which seven (PPV 41.2%) were malignant in six women. Mean size of the four invasive malignancies was 1.9 cm (range 0.7-4.1), all node negative; three lesions in two women were ductal carcinoma in situ. Nine biopsied lesions were benign, mean size 1.2 cm (range 0.6-2.0). All biopsied lesions were in women with dense breasts (heterogeneously or extremely dense on mammography, n = 367), for a cancer detection rate of 16.3/1000 examinations in this subpopulation. These data were used to identify four high-yield acquisitions: T2, T1-pre-contrast, T11.5, and T16 to create the AP with a scan time of 7.5 min compared to 24 min for the FDP. CONCLUSIONS: Our analysis of a FDP MRI in a mammographically negative group identified four high-yield acquisitions that could be used for rapid screening of women for breast cancer that retains critical information on morphology, histopathology, and kinetic activity to facilitate detection of suspicious lesions.
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Neoplasias de la Mama/diagnóstico por imagen , Neoplasias de la Mama/epidemiología , Detección Precoz del Cáncer , Imagen por Resonancia Magnética , Adulto , Anciano , Anciano de 80 o más Años , Densidad de la Mama , Neoplasias de la Mama/patología , Femenino , Humanos , Interpretación de Imagen Asistida por Computador , Imagen por Resonancia Magnética/métodos , Mamografía , Tamizaje Masivo , Persona de Mediana Edad , Estadificación de Neoplasias , Sensibilidad y EspecificidadRESUMEN
Chronic inflammation contributes to colorectal carcinogenesis. To determine whether serum cytokines are associated with colon polyps, 126 asymptomatic men (48-65 years) were recruited during colonoscopy. Serum cytokine concentrations were measured. Odds ratios were determined using polytomous logistic regression for polyp number and type. Men with serum monocyte chemotactic protein-3 (MCP-3) or soluble interleukin-4 receptor (sIL-4R) concentrations in the highest tertile were 0.2 times less likely to have three or more polyps relative to no polyps. For each increase in serum MCP-3 or sIL-4R tertile a man was about 0.4 times less likely to have three or more polyps than to have no polyps. Men with serum concentrations of interferon-α2 (IFN-α2) or interleukin (IL)-7 in the highest tertile were three times more likely to have an adenoma than no polyps. Those with serum IL-8 concentrations in the highest tertile were four times more likely to have an adenoma than no polyps. For each increase in serum IFN-α2, IL-7, or IL-8 tertile an individual was 1.8 times more likely to have an adenoma than to have no polyps. Serum concentrations of MCP-3, sIL-4R, IFN-α2, IL-7, and IL-8 may indicate which men are more likely to have colorectal polyps.
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Adenoma/diagnóstico , Pólipos del Colon/diagnóstico , Neoplasias Colorrectales/diagnóstico , Citocinas/sangre , Adenoma/sangre , Adulto , Anciano , Pólipos del Colon/sangre , Colonoscopía , Neoplasias Colorrectales/sangre , Humanos , Masculino , Persona de Mediana EdadRESUMEN
BACKGROUND: Dysregulated insulin signaling is thought to contribute to cancer risk. METHODS: To determine if insulin-related serum factors are associated with colon polyps, 126 asymptomatic men (48-65 years) were recruited at colonoscopy. Blood was collected. Odds ratios were determined using polytomous logistic regression for polyp number and type. RESULTS: Males with serum C-peptide concentration >3.3 ng/mL were 3.8 times more likely to have an adenoma relative to no polyp than those with C-peptide ≤1.8 ng/mL. As C-peptide tertile increased, an individual was 2 times more likely to have an adenoma (P = 0.01) than no polyp. There were no associations between insulin-like growth factor or its binding proteins with polyp number or type. Males with soluble receptor for advanced glycation end products (sRAGE) concentration >120.4 pg/mL were 0.25 times less likely to have ≥3 polyps relative to no polyps compared with males with sRAGE ≤94.5 pg/mL. For each increase in sRAGE tertile, a man was 0.5 times less likely to have ≥3 polyps than no polyps (P = 0.03). Compared with males with a serum vascular endothelial growth factor (VEGF) concentration ≤104.7 pg/mL, males with a serum VEGF concentration >184.2 pg/mL were 3.4 times more likely to have ≥3 polyps relative to no polyps. As the VEGF tertile increased, a man was 1.9 times more likely to have ≥3 polyps than no polyps (P = 0.049). CONCLUSIONS: Serum concentrations of C-peptide, sRAGE, and VEGF may indicate which men could benefit most from colonoscopy. IMPACT: Identification of biomarkers could reduce medical costs through the elimination of colonoscopies on low-risk individuals.
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Péptido C/sangre , Pólipos del Colon/sangre , Pólipos del Colon/patología , Insulina/sangre , Adenoma/sangre , Adenoma/patología , Anciano , Colonoscopía/métodos , Neoplasias Colorrectales/sangre , Neoplasias Colorrectales/patología , Productos Finales de Glicación Avanzada/sangre , Humanos , Modelos Logísticos , Masculino , Persona de Mediana Edad , Somatomedinas/metabolismo , Factor A de Crecimiento Endotelial Vascular/sangreRESUMEN
Diverticulosis can lead to diverticulitis, a colon condition involving inflammation and other complications. Diverticulosis can result from biological, behavioral, or genetic causes. However, the etiology of diverticulosis is unknown. Although diet is associated with diverticulosis, recent studies suggest other factors influence risk. We sought to identify anthropometric or serum markers that were associated with the presence of diverticulosis. To determine these associations, 126 asymptomatic men (48-65 yr) were recruited at the time of preventative screening colonoscopy. Anthropometric measures were taken, and blood was collected for serum protein analysis. Data were analyzed by logistic regression and factor analysis. Obese individuals (BMI >30) were 7.8 (CI: 2.3-26.3) times more likely than normal weight (BMI <25) individuals to have diverticulosis. The relationship was similar for waist circumference. Individuals with a waist circumference >45 inches were 8.1 (CI: 2.8-23.8) times more likely to have diverticulosis than those with a waist circumference <38 inches. Leptin was also positively associated with diverticulosis (OR = 5.5, CI: 2.0-14.7). Both low molecular weight adiponectin (LMW, OR = 0.50; CI: 0.3-0.8) and the soluble receptor for advanced glycation end products (sRAGE, OR = 0.4, CI: 0.3-0.7) were inversely related to the presence of diverticulosis. sRAGE levels were not correlated with leptin or C-peptide concentrations. The pattern of high BMI, waist circumference, leptin and C-peptide increased the odds of diverticulosis while the pattern of high levels of sRAGE and LMW adiponectin decreased the odds of diverticulosis. Associations between diverticulosis and anthropometric or serum markers may elucidate the origins of diverticulosis and may enable physicians to identify individuals at risk for diverticulitis.
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Adiponectina/sangre , Divertículo/sangre , Obesidad/sangre , Receptores Inmunológicos/sangre , Anciano , Antropometría , Enfermedades Asintomáticas , Biomarcadores/sangre , Índice de Masa Corporal , Péptido C/sangre , Colonoscopía , Estudios Transversales , Divertículo/complicaciones , Divertículo/diagnóstico , Análisis Factorial , Humanos , Leptina/sangre , Modelos Logísticos , Masculino , Persona de Mediana Edad , Obesidad/complicaciones , Obesidad/diagnóstico , Receptor para Productos Finales de Glicación Avanzada , Circunferencia de la CinturaRESUMEN
BACKGROUND: Obesity increases the risk of colon cancer. It is also known that most colorectal cancers develop from adenomatous polyps. However, the effects of obesity and adipokines on colonic polyp formation are unknown. METHODS: To determine if BMI, waist circumference or adipokines are associated with colon polyps in males, 126 asymptomatic men (48-65 yr) were recruited at time of colonoscopy, and anthropometric measures as well as blood were collected. Odds ratios were determined using polytomous logistic regression for polyp number (0 or ≥3) and polyp type (no polyp, hyperplastic polyp, tubular adenoma). RESULTS: 41% of the men in our study were obese (BMI ≥30). The odds of an obese individual having ≥3 polyps was 6.5 (CI: 1.3-33.0) times greater than those of a lean (BMI<25) individual. Additionally, relative to lean individuals, obese individuals were 7.8 (CI: 2.0-30.8) times more likely to have a tubular adenoma than no polyp. As BMI category increased, participants were 2.9 (CI: 1.5-5.4) times more likely to have a tubular adenoma than no polyps. Serum leptin, IP-10 and TNF-α were significantly associated with tubular adenoma presence. Serum leptin and IP-10 were significantly associated with increased likelihood of ≥3 polyps, and TNF-α showed a trend (pâ=â0.09). CONCLUSIONS: Obese men are more likely to have at least three polyps and adenomas. This cross-sectional study provides evidence that colonoscopy should be recommended for obese, white males.
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Pólipos Adenomatosos/sangre , Pólipos Adenomatosos/complicaciones , Adipoquinas/sangre , Obesidad/sangre , Obesidad/complicaciones , Adenoma/sangre , Adenoma/patología , Adulto , Anciano , Índice de Masa Corporal , Estudios Transversales , Humanos , Hiperplasia , Masculino , Persona de Mediana Edad , Circunferencia de la CinturaRESUMEN
OBJECTIVES: The purpose of this study was to determine if cholesterol crystals can injure the endothelial surface by their jagged edges altering vasoreactivity and contributing to no-reflow after intervention. BACKGROUND: After plaque rupture, cholesterol crystals are released into the circulation and flow downstream contacting the arterial wall. METHODS: Both carotid arteries from 22 rabbits were placed in a dual perfusion chamber and challenged with norepinephrine followed by acetylcholine and nitroprusside. Arterial diameters were measured before and after exposure to cholesterol crystals or microspheres and compared with diameters of normal control arteries. Arteries were examined by light, confocal, atomic force and scanning electron microscopy. RESULTS: Pre-exposure mean arterial diameter was 2.33 ± 0.27 mm. With baseline norepinephrine there was vasoconstriction of 0.82 ± 0.19 mm, 0.79 ± 0.18 mm, and 0.83 ± 0.16 mm in lumen diameter in the crystal, microsphere, and control groups, respectively. After cholesterol crystals or microspheres, vasoconstriction was significantly less for cholesterol crystals but not for microspheres (0.71 ± 0.28 mm and 0.81 ± 0.15 mm; p < 0.02 and p = 0.68). After acetylcholine in the same artery, there was significantly less dilation before versus after crystals (0.49 ± 0.24 mm vs. 0.38 ± 0.22 mm, p = 0.04) but not with microspheres or in the control group. There was no significant difference after nitroprusside in any group, suggesting endothelial injury. By scanning electron microscopy, cholesterol crystals were found embedded in the intima with endothelial cell tears whereas the microsphere treatment and control groups had minimal or no injury (93% vs. 31% vs. 14%; p < 0.01). By atomic force microscopy, surface roughness was significantly greater with cholesterol crystals compared with microspheres or in control arteries (p < 0.05). CONCLUSIONS: Cholesterol crystals damaged the endothelium and reduced vasodilator response, potentially aggravating myocardial ischemia after interventions.
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Traumatismos de las Arterias Carótidas/etiología , Colesterol/efectos adversos , Endotelio Vascular/lesiones , Fenómeno de no Reflujo/etiología , Lesiones del Sistema Vascular/etiología , Vasoconstricción , Vasodilatación , Acetilcolina/farmacología , Animales , Traumatismos de las Arterias Carótidas/sangre , Traumatismos de las Arterias Carótidas/patología , Traumatismos de las Arterias Carótidas/fisiopatología , Colesterol/sangre , Colesterol/química , Cristalización , Endotelio Vascular/efectos de los fármacos , Endotelio Vascular/fisiopatología , Microscopía de Fuerza Atómica , Microscopía Confocal , Microscopía Electrónica de Rastreo , Microesferas , Nitroprusiato/farmacología , Fenómeno de no Reflujo/sangre , Fenómeno de no Reflujo/fisiopatología , Norepinefrina/farmacología , Conejos , Lesiones del Sistema Vascular/sangre , Lesiones del Sistema Vascular/patología , Lesiones del Sistema Vascular/fisiopatología , Vasoconstricción/efectos de los fármacos , Vasoconstrictores/farmacología , Vasodilatación/efectos de los fármacos , Vasodilatadores/farmacologíaRESUMEN
Fetal growth or gestational age in a woman's pregnancies may modify pregnancy-related breast cancer risk, yet studies of these exposures are few. The authors conducted a population-based case-control study among parous Michigan women aged ≤50 years using linked Michigan Cancer Registry (1985-2004) and Michigan livebirth records (1978-2004). Breast cancer cases (n = 7,591) were matched 1:4 to controls (n = 28,382) on maternal birth year and race. Using conditional logistic regression, the authors examined the associations of gestational age (in weeks) and fetal growth (defined using birth weight percentiles for gestational age) in first and last births with breast cancer risk. Having a small-for-gestational-age or large-for-gestational-age infant at a maternal first or last birth was not associated with breast cancer risk, but having a small-for-gestational-age infant at a last birth at ≥30 years modestly reduced risk: odds ratio = 0.82 (95% confidence interval: 0.68, 0.98). First delivery at <32 or >41 weeks also modestly reduced risk: odds ratio = 0.80 (95% confidence interval: 0.62, 1.04) or 0.92 (95% confidence interval: 0.85, 0.99), respectively. In the largest case-control study to date, fetal growth was not associated with overall breast cancer risk in women aged ≤50, and there was some evidence for reduced breast cancer risk for early or late gestational age in first births only.
Asunto(s)
Neoplasias de la Mama/epidemiología , Desarrollo Fetal , Edad Gestacional , Adulto , Peso al Nacer , Carcinoma Ductal de Mama/epidemiología , Carcinoma Lobular/epidemiología , Estudios de Casos y Controles , Femenino , Humanos , Persona de Mediana Edad , Embarazo , Factores de Riesgo , Factores SocioeconómicosRESUMEN
BACKGROUND: The long-term goal of the GKDZI (Genetics of Kidney Disease in Zuni Indians) Study is to identify genes, environmental factors, and genetic-environmental interactions that modulate susceptibility to renal disease and intermediate phenotypes. STUDY DESIGN: A community-based participatory research approach was used to recruit family members of individuals with kidney disease. SETTING & PARTICIPANTS: The study was conducted in the Zuni Indians, a small endogamous tribe located in rural New Mexico. We recruited members of extended families, ascertained through a proband with kidney disease and at least 1 sibling with kidney disease. 821 participants were recruited, comprising 7,702 relative pairs. PREDICTOR OUTCOMES & MEASUREMENTS: Urine albumin-creatinine ratio (UACR) and hematuria were determined in 3 urine samples and expressed as a true ratio. Glomerular filtration rate (GFR) was estimated using the Modification of Diet in Renal Disease (MDRD) Study equation modified for American Indians. Probands were considered to have kidney disease if UACR was >or=0.2 in 2 or more of 3 spot urine samples or estimated GFR was decreased according to the CRIC (Chronic Renal Insufficiency Cohort) Study criteria. RESULTS: Kidney disease was identified in 192 participants (23.4%). There were significant heritabilities for estimated GFR, UACR, serum creatinine, serum urea nitrogen, and uric acid and a variety of phenotypes related to obesity, diabetes, and cardiovascular disease. There were significant genetic correlations of some kidney-related phenotypes with these other phenotypes. LIMITATIONS: Limitations include absence of renal biopsy, possible misclassification bias, lack of direct GFR measurements, and failure to include all possible environmental interactions. CONCLUSIONS: Many phenotypes related to kidney disease showed significant heritabilities in Zuni Indians, and there were significant genetic correlations with phenotypes related to obesity, diabetes, and cardiovascular disease. The study design serves as a paradigm for the conduct of research in relatively isolated, endogamous, underserved populations.
Asunto(s)
Predisposición Genética a la Enfermedad/etnología , Insuficiencia Renal Crónica/etnología , Insuficiencia Renal Crónica/genética , Albúminas/metabolismo , Nitrógeno de la Urea Sanguínea , Investigación Participativa Basada en la Comunidad , Creatinina/orina , Nefropatías Diabéticas/etnología , Nefropatías Diabéticas/genética , Ligamiento Genético , Tasa de Filtración Glomerular , Hematuria/etnología , Humanos , Indígenas Norteamericanos , New Mexico , Obesidad/etnología , Obesidad/genética , Fenotipo , Carácter Cuantitativo HeredableRESUMEN
BACKGROUND: The importance of Hepatitis C (HCV) as a public and individual health concern is well established. However, national groups differ in their recommendations to primary care clinicians about screening people at high risk for HCV. The purpose of this study was to explore the context of care within which primary care clinicians decide to detect and initially manage HCV. METHODS: The Primary Care Multiethnic Network conducted a web- and paper-based survey of primary care clinicians who largely practice in low-income, medically underserved communities in 3 regions across the country. RESULTS: A total of 494 clinicians participated, for a response rate of 61%. Most (68%) clinicians view HCV as an important problem; more than half (59%) consider screening for HCV to be important when compared with other conditions they screen for in practice. With regard to reported screening habits for risk factors, 54% of clinicians routinely ask new patients whether they have used intravenous drugs and 28% inquire about blood transfusions before 1992. Sixty-one percent order an alanine aminotransferase test when patients present with other risk factors for HCV. The majority of clinicians (54%) refer 75% or fewer of their patients with HCV for treatment; nearly one-fifth (18%) provide antiviral treatment themselves. Key factors influencing clinician HCV decision making are patient comorbidities (74% reported this as a factor), access to treatment (55% reported this as a factor), and tolerance (44% reported this as a factor) of treatment. CONCLUSIONS: In the face of conflicting national guideline recommendations about screening people at high risk for HCV, clinicians have varied views and practice habits influenced by multiple patient, access, and treatment issues.
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Hepatitis C/diagnóstico , Área sin Atención Médica , Atención Primaria de Salud/estadística & datos numéricos , Toma de Decisiones , Humanos , Tamizaje MasivoRESUMEN
OBJECTIVE: The purpose of this study was to analyze functional polymorphisms in candidate genes (methylenetetrahydrofolate reductase [MTHFR]677C>T, MTHFR1298A>C, factor 5 1691G>A [FVL], and angiotensinogen (AGT)-6G>A) in relation to a hypothesized placental hemorrhage pathway to preterm delivery (PTD). STUDY DESIGN: We assessed maternal genotypes, pregnancy outcomes, and placental pathologic evidence among 560 white and 399 black women who were recruited at mid trimester into a prospective cohort study (1998-2004). Odds of dominant genotypes were calculated for PTDs with (n = 56) or without (n = 177) evidence of placental hemorrhage (referent = term) with the use of race-stratified polytomous logistic regression models. RESULTS: Among white women, FVL GA/AA and AGT(-6) GA/AA were both associated with hemorrhage-related PTDs (odds ratio [OR], 4.8; 95% confidence interval [CI], 1.6-14.2 and OR, 3.8; 95% CI, 1.3-10.5, respectively), but not other PTDs (ORs, 1.2 and 0.9, respectively). FVL GA/AA was associated with placental abruption (OR, 5.8; 95% CI, 1.1-30) among white women. All results were null for MTHFR genotypes. CONCLUSION: FVL and AGT variant genotypes were associated specifically with hemorrhage-related PTDs.