RESUMEN
Experimental studies suggest that abnormal levels of Ca, Mg and phosphorus are implicated in pancreatic carcinogenesis. We investigated the associations between intakes of these minerals and the risk of pancreatic cancer in a case-control study conducted in 1994-1998. Cases of pancreatic cancer (n 150) were recruited from all hospitals in the metropolitan area of the Twin Cities and Mayo Clinic, Minnesota. Controls (n 459) were randomly selected from the general population and frequency matched to cases by age, sex and race. All dietary variables were adjusted for energy intake using the residual method prior to data analysis. Logistic regression was performed to evaluate the associations between intake of three nutrients examined and the risk of pancreatic cancer. Total intake of Ca (936 v. 1026 mg/d) and dietary intake of Mg (315 v. 331 mg/d) and phosphorus (1350 v. 1402 mg/d) were significantly lower in cases than in controls. After adjustment for confounders, there were not significant associations of total and dietary intakes of Ca, Mg and phosphorus with the risk of pancreatic cancer. In addition, no significant interactions exist between intakes of these minerals and total fat on pancreatic cancer risk. In conclusion, the present study does not suggest that intakes of Ca, Mg and phosphorus were significantly associated with the risk of pancreatic cancer.
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Calcio de la Dieta/administración & dosificación , Magnesio , Neoplasias Pancreáticas , Fósforo/administración & dosificación , Estudios de Casos y Controles , Dieta , Humanos , Magnesio/administración & dosificación , Minerales , Minnesota/epidemiología , Neoplasias Pancreáticas/epidemiología , Neoplasias Pancreáticas/etiología , Neoplasias PancreáticasRESUMEN
BACKGROUND/OBJECTIVES: Folate, vitamin B6, vitamin B12, and methionine are involved in DNA synthesis and methylation and thus may modulate pancreatic cancer risk. We investigated these associations in a population-based case-control study conducted in 1994-1998. SUBJECTS/METHODS: Cases (n = 150) were identified from all hospitals in the metropolitan areas of the Twin Cities and the Mayo Clinic, Minnesota. Controls (n = 459) were selected randomly from the general population and were frequency matched to cases by age, sex, and race. Logistic regression was used to estimate odds ratios (OR) and 95% confidence intervals (95% CI) for risk of pancreatic cancer in relation to intake of nutrients considered. RESULTS: Dietary intake of folate was associated with a reduced pancreatic cancer risk [OR (95% CI) for quartile (Q) 4 vs. Q1: 0.31 (0.12-0.78)]. A composite score (range from 2 to 8), reflecting combined dietary intake of folate and vitamin B6, was also inversely associated with pancreatic cancer risk [OR (95% CI) for Q4 vs. Q1: 0.24 (0.08-0.70)]. Null associations were found for intake of vitamin B12 and methionine. CONCLUSIONS: Dietary folate intake was associated with a reduced pancreatic cancer risk, and this association became stronger when dietary intake of folate and vitamin B6 was combined in analysis.
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Dieta , Ácido Fólico/administración & dosificación , Metionina/administración & dosificación , Neoplasias Pancreáticas/epidemiología , Vitamina B 12/administración & dosificación , Vitamina B 6/administración & dosificación , Adulto , Anciano , Estudios de Casos y Controles , Metilación de ADN/fisiología , Suplementos Dietéticos , Femenino , Humanos , Masculino , Persona de Mediana Edad , Minnesota/epidemiología , Oportunidad Relativa , Neoplasias Pancreáticas/prevención & control , Factores de RiesgoRESUMEN
Pancreatic cancer is one of the most fatal common cancers affecting both men and women, representing about 3% of all new cancer cases in the United States. In this study, we aimed to investigate the association of pancreatic cancer risk with alcohol consumption as well as folate intake. We performed a case-control study of 384 patients diagnosed with pancreatic cancer from May 2004 to December 2009 and 983 primary care healthy controls in a largely white population (>96%). Our findings showed no significant association between risk of pancreatic cancer and either overall alcohol consumption or type of alcohol consumed (drinks/day). Our study showed dietary folate intake had a modest effect size, but was significantly inversely associated with pancreatic cancer (odds ratio (OR) = 0.99, p < 0.0001). The current study supports the hypothesis that pancreatic cancer risk is reduced with higher food-based folate intake.
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Consumo de Bebidas Alcohólicas/efectos adversos , Dieta , Ácido Fólico/administración & dosificación , Neoplasias Pancreáticas/epidemiología , Anciano , Índice de Masa Corporal , Estudios de Casos y Controles , Suplementos Dietéticos , Femenino , Humanos , Masculino , Persona de Mediana Edad , Estado Nutricional , Factores de RiesgoRESUMEN
The discovery of the (+)-α-thujone and (-)-ß-thujone stereoisomers in the essential oil of sage (Salvia officinalis L.) and dietary supplements is documented for the first time. The detection was accomplished using a chiral resolution protocol of racemic α-/ß-thujone on headspace solid-phase microextraction-gas chromatography-mass spectrometry. Because the previously unreported stereoisomers, (+)-α-thujone and (-)-ß-thujone, are not commercially available, a three-step synthesis of racemic thujone from commercially available starting materials was developed. Thermolysis studies demonstrated that no racemization at the cyclopropane stereocenters occurs, corroborating that the detection is not an artifact from the hydrodistillation process. The developed chiral resolution of thujone was also used to provide evidence for the absence of the (+)-α-thujone and (-)-ß-thujone enantiomers in other common thujone-containing essential oils.
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Cromatografía de Gases y Espectrometría de Masas/métodos , Monoterpenos/química , Aceites Volátiles/química , Aceites de Plantas/química , Salvia officinalis/química , Microextracción en Fase Sólida/métodos , Monoterpenos Bicíclicos , Monoterpenos/aislamiento & purificación , Aceites Volátiles/aislamiento & purificación , Aceites de Plantas/aislamiento & purificación , EstereoisomerismoRESUMEN
BACKGROUND: Breast cancer aetiology may differ by estrogen receptor (ER) status. Associations of alcohol and folate intakes with risk of breast cancer defined by ER status were examined in pooled analyses of the primary data from 20 cohorts. METHODS: During a maximum of 6-18 years of follow-up of 1 089 273 women, 21 624 ER+ and 5113 ER- breast cancers were identified. Study-specific multivariable relative risks (RRs) were calculated using Cox proportional hazards regression models and then combined using a random-effects model. RESULTS: Alcohol consumption was positively associated with risk of ER+ and ER- breast cancer. The pooled multivariable RRs (95% confidence intervals) comparing ≥ 30 g/d with 0 g/day of alcohol consumption were 1.35 (1.23-1.48) for ER+ and 1.28 (1.10-1.49) for ER- breast cancer (Ptrend ≤ 0.001; Pcommon-effects by ER status: 0.57). Associations were similar for alcohol intake from beer, wine and liquor. The associations with alcohol intake did not vary significantly by total (from foods and supplements) folate intake (Pinteraction ≥ 0.26). Dietary (from foods only) and total folate intakes were not associated with risk of overall, ER+ and ER- breast cancer; pooled multivariable RRs ranged from 0.98 to 1.02 comparing extreme quintiles. Following-up US studies through only the period before mandatory folic acid fortification did not change the results. The alcohol and folate associations did not vary by tumour subtypes defined by progesterone receptor status. CONCLUSIONS: Alcohol consumption was positively associated with risk of both ER+ and ER- breast cancer, even among women with high folate intake. Folate intake was not associated with breast cancer risk.
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Consumo de Bebidas Alcohólicas/epidemiología , Neoplasias de la Mama/epidemiología , Receptores de Estrógenos/genética , Adulto , Anciano , Anciano de 80 o más Años , Neoplasias de la Mama/genética , Suplementos Dietéticos , Etanol/metabolismo , Femenino , Ácido Fólico/metabolismo , Humanos , Persona de Mediana Edad , Análisis Multivariante , Modelos de Riesgos Proporcionales , Estudios Prospectivos , Factores de Riesgo , Encuestas y Cuestionarios , Adulto JovenRESUMEN
PURPOSE: Vitamins A, C, and E and folate have anticarcinogenic properties and thus might protect against cancer. Few known modifiable risk factors for ovarian cancer exist. We examined the associations between dietary and total (food and supplemental) vitamin intake and the risk of invasive epithelial ovarian cancer. METHODS: The primary data from 10 prospective cohort studies in North America and Europe were analyzed. Vitamin intakes were estimated from validated food frequency questionnaires in each study. Study-specific relative risks (RRs) were estimated using the Cox proportional hazards model and then combined using a random-effects model. RESULTS: Among 501,857 women, 1,973 cases of ovarian cancer occurred over a median follow-up period of 7-16 years across studies. Dietary and total intakes of each vitamin were not significantly associated with ovarian cancer risk. The pooled multivariate RRs [95% confidence intervals (CIs)] for incremental increases in total intake of each vitamin were 1.02 (0.97-1.07) for vitamin A (increment: 1,300 mcg/day), 1.01 (0.99-1.04) for vitamin C (400 mg/day), 1.02 (0.97-1.06) for vitamin E (130 mg/day), and 1.01 (0.96-1.07) for folate (250 mcg/day). Multivitamin use (vs. nonuse) was not associated with ovarian cancer risk (pooled multivariate RR = 1.00, 95% CI 0.89-1.12). Associations did not vary substantially by study, or by subgroups of the population. Greater vitamin intakes were associated with modestly higher risks of endometrioid tumors (n = 156 cases), but not with other histological types. CONCLUSION: These results suggest that consumption of vitamins A, C, and E and folate during adulthood does not play a major role in ovarian cancer risk.
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Ácido Ascórbico/efectos adversos , Suplementos Dietéticos/efectos adversos , Ácido Fólico/efectos adversos , Neoplasias Glandulares y Epiteliales/epidemiología , Neoplasias Glandulares y Epiteliales/etiología , Neoplasias Ováricas/epidemiología , Neoplasias Ováricas/etiología , Vitamina A/efectos adversos , Vitamina E/efectos adversos , Vitaminas/efectos adversos , Adulto , Carcinoma Epitelial de Ovario , Estudios de Cohortes , Europa (Continente)/epidemiología , Femenino , Humanos , Persona de Mediana Edad , América del Norte/epidemiología , Estudios Prospectivos , RiesgoRESUMEN
Although many studies have investigated meat and total fat in relation to pancreatic cancer risk, few have investigated dairy, fish and specific fatty acids (FAs). We evaluated the association between intake of meat, fish, dairy, specific FAs and related nutrients and pancreatic cancer. In our American-based Mayo Clinic case-control study 384 cases and 983 controls frequency matched on recruitment age, race, sex and residence area (Minnesota, Wisconsin or Iowa, USA) between 2004 and 2009. All subjects provided demographic information and completed 144-item food frequency questionnaire. Logistic regression-calculated odds ratios (ORs) and 95% confidence intervals (95% CIs) were adjusted for age, sex, cigarette smoking, body mass index and diabetes mellitus. Significant inverse association (trend p-value < 0.05) between pancreatic cancer and the groupings (highest vs. lowest consumption quintile OR [95% CI]) was as follows: meat replacement (0.67 [0.43-1.02]), total protein (0.58 [0.39-0.86]), vitamin B12 (0.67 [0.44, 1.01]), zinc (0.48 [0.32, 0.71]), phosphorus (0.62 [0.41, 0.93]), vitamin E (0.51 [0.33, 0.78]), polyunsaturated FAs (0.64 [0.42, 0.98]) and linoleic acid (FA 18:2) (0.62 [0.40-0.95]). Increased risk associations were observed for saturated FAs (1.48 [0.97-2.23]), butyric acid (FA 4:0) (1.77 [1.19-2.64]), caproic acid (FA 6:0) (2.15 [1.42-3.27]), caprylic acid (FA 8:0) (1.87 [1.27-2.76]) and capric acid (FA 10:0) (1.83 [1.23-2.74]). Our study suggests that eating a diet high in total protein and certain unsaturated FAs is associated with decreased risk of developing pancreatic cancer in a dose-dependent manner, whereas fats found in dairy increase risk.
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Productos Lácteos/análisis , Grasas de la Dieta/análisis , Ácidos Grasos Insaturados/análisis , Neoplasias Pancreáticas/epidemiología , Proteínas/análisis , Anciano , Estudios de Casos y Controles , Dieta , Conducta Alimentaria , Femenino , Humanos , Masculino , Carne/análisis , Factores de Riesgo , Encuestas y CuestionariosRESUMEN
PURPOSE: Pancreatic cancer is a devastating disease for which the role of dietary factors remains inconclusive. Our objective was to evaluate the risk of pancreatic cancer associated with nutrients found in fruits and vegetables and nutrient supplementation using a clinic-based case-control design. METHODS: Our study included 384 rapidly ascertained cases and 983 controls frequency-matched on age at time of recruitment (in 5-year increments), race, sex, and region of residence. All subjects provided demographic information and completed a 144-item food frequency questionnaire in which they reported no change to their diet within 5 years prior to entering the study. Logistic regression was used to calculate odds ratios and 95 % confidence intervals, adjusted for age, sex, smoking, body mass index, energy intake, and alcohol consumption. RESULTS: Results show a significant (trend p value < 0.05) inverse association between pancreatic cancer and nutrient/supplement groupings in a dose-dependent manner including magnesium, potassium, selenium, alpha-carotene, beta-carotene, beta-cryptoxanthin, lutein and zeaxanthin, niacin, total alpha-tocopherol, total vitamin A activity, vitamin B6, and vitamin C. Adjusting for diabetes or total sugar intake did not result in significant changes. CONCLUSION: We conclude that most nutrients obtained through consumption of fruits and vegetables may reduce the risk of developing pancreatic cancer.
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Adenocarcinoma/epidemiología , Dieta , Frutas , Neoplasias Pancreáticas/epidemiología , Verduras , Anciano , Estudios de Casos y Controles , Suplementos Dietéticos , Femenino , Humanos , Masculino , Oportunidad Relativa , Factores de Riesgo , Encuestas y CuestionariosRESUMEN
Ingested nitrate can be endogenously reduced to nitrite, which may form N-nitroso compounds, known potent carcinogens. However, some studies have reported no or inverse associations between dietary nitrate intake and cancer risk. These associations may be confounded by a protective effect of folate, which plays a vital role in DNA repair. We evaluated the interaction of dietary and water nitrate intake with total folate intake on breast cancer risk in the Iowa Women's Health Study. Dietary intake was assessed at study baseline. Nitrate intake from public water was assessed using a historical database on Iowa municipal water supplies. After baseline exclusions, 34,388 postmenopausal women and 2,875 incident breast cancers were included. Overall, neither dietary nor water nitrate was associated with breast cancer risk. Among those with folate intake ≥400 µg/day, breast cancer risk was significantly increased in public water users with the highest nitrate quintile (HR = 1.40, 95% CI = 1.05-1.87) and private well users (HR = 1.38, 95% CI = 1.05-1.82) compared to public water users with the lowest nitrate quintile; in contrast, there was no association among those with lower folate intake. Our findings do not support a previous report of increased risk of breast cancer among individuals with high dietary nitrate but low folate intake.
Asunto(s)
Neoplasias de la Mama/etiología , Dieta , Agua Potable/química , Ácido Fólico/administración & dosificación , Nitratos/administración & dosificación , Anciano , Neoplasias de la Mama/inducido químicamente , Neoplasias de la Mama/epidemiología , Neoplasias de la Mama/prevención & control , Estudios de Cohortes , Dieta/efectos adversos , Encuestas sobre Dietas , Suplementos Dietéticos/efectos adversos , Agua Potable/efectos adversos , Femenino , Ácido Fólico/efectos adversos , Ácido Fólico/uso terapéutico , Aditivos Alimentarios/administración & dosificación , Aditivos Alimentarios/efectos adversos , Aditivos Alimentarios/análisis , Humanos , Incidencia , Iowa/epidemiología , Persona de Mediana Edad , Nitratos/efectos adversos , Nitratos/análisis , Nitratos/toxicidad , Posmenopausia , Estudios Prospectivos , Sistema de Registros , Riesgo , Contaminantes Químicos del Agua/administración & dosificación , Contaminantes Químicos del Agua/análisis , Contaminantes Químicos del Agua/toxicidadRESUMEN
BACKGROUND: Coffee has been hypothesized to have pro- and anticarcinogenic properties, whereas tea may contain anticarcinogenic compounds. Studies assessing coffee intake and pancreatic cancer risk have yielded mixed results, whereas findings for tea intake have mostly been null. Sugar-sweetened carbonated soft drink (SSB) intake has been associated with higher circulating levels of insulin, which may promote carcinogenesis. Few prospective studies have examined SSB intake and pancreatic cancer risk; results have been heterogeneous. METHODS: In this pooled analysis from 14 prospective cohort studies, 2,185 incident pancreatic cancer cases were identified among 853,894 individuals during follow-up. Multivariate (MV) study-specific relative risks (RR) and 95% confidence intervals (CI) were calculated using Cox proportional hazards models and then pooled using a random-effects model. RESULTS: No statistically significant associations were observed between pancreatic cancer risk and intake of coffee (MVRR = 1.10; 95% CI, 0.81-1.48 comparing ≥900 to <0 g/d; 237g ≈ 8oz), tea (MVRR = 0.96; 95% CI, 0.78-1.16 comparing ≥400 to 0 g/d; 237g ≈ 8oz), or SSB (MVRR = 1.19; 95% CI, 0.98-1.46 comparing ≥250 to 0 g/d; 355g ≈ 12oz; P value, test for between-studies heterogeneity > 0.05). These associations were consistent across levels of sex, smoking status, and body mass index. When modeled as a continuous variable, a positive association was evident for SSB (MVRR = 1.06; 95% CI, 1.02-1.12). CONCLUSION AND IMPACT: Overall, no associations were observed for intakes of coffee or tea during adulthood and pancreatic cancer risk. Although we were only able to examine modest intake of SSB, there was a suggestive, modest positive association for risk of pancreatic cancer for intakes of SSB.
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Carbohidratos/administración & dosificación , Bebidas Gaseosas/estadística & datos numéricos , Café , Neoplasias Pancreáticas/epidemiología , Té , Adulto , Estudios de Cohortes , Humanos , Masculino , Estudios Prospectivos , Factores de Riesgo , Adulto JovenRESUMEN
BACKGROUND: Epidemiological studies evaluating the association between folate intake and risk of pancreatic cancer have produced inconsistent results. The statistical power to examine this association has been limited in previous studies partly because of small sample size and limited range of folate intake in some studies. METHODS: We analyzed primary data from 14 prospective cohort studies that included 319,716 men and 542,948 women to assess the association between folate intake and risk of pancreatic cancer. Folate intake was assessed through a validated food-frequency questionnaire at baseline in each study. Study-specific relative risks (RRs) and 95% confidence intervals (CIs) were estimated using Cox proportional hazards models and then pooled using a random effects model. All statistical tests were two-sided. RESULTS: During 7-20 years of follow-up across studies, 2195 pancreatic cancers were identified. No association was observed between folate intake and risk of pancreatic cancer in men and women (highest vs lowest quintile: dietary folate intake, pooled multivariable RR = 1.06, 95% CI = 0.90 to 1.25, P(trend) = .47; total folate intake [dietary folate and supplemental folic acid], pooled multivariable RR = 0.96, 95% CI = 0.80 to 1.16, P(trend) = .90). No between-study heterogeneity was observed (for dietary folate, P(heterogeneity) = .15; for total folate, P(heterogeneity) = .22). CONCLUSION: Folate intake was not associated with overall risk of pancreatic cancer in this large pooled analysis.
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Conducta Alimentaria , Ácido Fólico/administración & dosificación , Ácido Fólico/farmacología , Neoplasias Pancreáticas/prevención & control , Estudios de Cohortes , Factores de Confusión Epidemiológicos , Femenino , Estudios de Seguimiento , Humanos , Masculino , Análisis Multivariante , Oportunidad Relativa , Modelos de Riesgos Proporcionales , Estudios Prospectivos , Medición de Riesgo , Encuestas y CuestionariosRESUMEN
Experimental evidence suggests that vitamin D has anticarcinogenic properties; however, a nested case-control study conducted in a population of male Finnish smokers found that higher 25-hydroxyvitamin D [25(OH)D], the best indicator of vitamin D status as determined by the sun and diet, was associated with a significant 3-fold increased risk for pancreatic cancer. We conducted a nested case-control study in the Prostate, Lung, Colorectal, and Ovarian Screening Trial cohort of men and women 55 to 74 years of age at baseline to test whether prediagnostic serum 25(OH)D concentrations were associated with pancreatic cancer risk. Between 1994 and 2006, 184 incident cases of pancreatic adenocarcinoma occurred (follow-up to 11.7 years). Two controls (n = 368) who were alive at the time the case was diagnosed were selected for each case and matched by age, race, sex, and calendar date of blood draw (to control for seasonal variation). We calculated odds ratios (OR) and 95% confidence intervals (95% CI) using conditional logistic regression, adjusting for smoking and body mass index. Vitamin D concentrations were not associated with pancreatic cancer overall (highest versus lowest quintile, >82.3 versus <45.9 nmol/L: OR, 1.45; 95% CI, 0.66-3.15; P trend = 0.49). However, positive associations were observed among subjects with low estimated annual residential solar UBV exposure, but not among those with moderate to high annual exposure (P interaction = 0.015). We did not confirm the previous strong positive association between 25(OH)D and pancreatic cancer; however, the increased risk among participants with low residential UVB exposure is similar.
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Adenocarcinoma/epidemiología , Calcifediol/sangre , Neoplasias Colorrectales/secundario , Neoplasias Pulmonares/secundario , Neoplasias Ováricas/secundario , Neoplasias Pancreáticas/epidemiología , Neoplasias de la Próstata/secundario , Vitamina D/sangre , Adenocarcinoma/complicaciones , Anciano , Estudios de Cohortes , Neoplasias Colorrectales/patología , Suplementos Dietéticos , Femenino , Humanos , Incidencia , Neoplasias Pulmonares/patología , Masculino , Persona de Mediana Edad , Metástasis de la Neoplasia/patología , Neoplasias Ováricas/patología , Neoplasias Pancreáticas/sangre , Neoplasias Pancreáticas/complicaciones , Neoplasias de la Próstata/patología , Factores de Riesgo , Factores Socioeconómicos , Luz Solar , Deficiencia de Vitamina D/epidemiologíaRESUMEN
Nutrigenomics is concerned with the role of nutrients in gene expression, and nutrigenetics is the study of how genetic variants or polymorphisms (mutations) can affect responses to nutrients; nutritional genomics is the umbrella term. Nutritional genomics can be expected to revolutionize the way dietitians and other health professionals identify people with chronic diseases and treat those diseases. Understanding the science of nutritional genomics is important to dietitians and other health professionals because major scientific advancements such as this usually have a significant impact on ethics, policy, and practice. Blood lipid profiles are one area in which nutritional genomics has quickly advanced knowledge. New knowledge is available on blood lipid profiles and associated conditions, such as obesity and type 2 diabetes. New technology has also had an impact on policy and practice issues, and ethics is an important issue to consider.
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Dietética/métodos , Nutrigenómica/métodos , Terapia Nutricional/normas , Fenómenos Fisiológicos de la Nutrición/genética , Dietética/ética , Regulación de la Expresión Génica , Humanos , Nutrigenómica/éticaRESUMEN
Laboratory data suggest that caffeine or some components of coffee may cause DNA mutations and inhibit tumor suppressor mechanisms, leading to neoplastic growth. However, coffee consumption has not been clearly implicated in the etiology of human postmenopausal ovarian cancer. This study evaluated the relationship of coffee and caffeine intake with risk of epithelial ovarian cancer in a prospective cohort study of 29,060 postmenopausal women. The participants completed a mailed questionnaire that assessed diet and health history and were followed for ovarian cancer incidence from 1986 to 2004. Age-adjusted and multivariate-adjusted hazard ratios were calculated for four exposure variables: caffeinated coffee, decaffeinated coffee, total coffee, and total caffeine to assess whether or not coffee or caffeine influences the risk of ovarian cancer. An increased risk was observed in the multivariate model for women who reported drinking five or more cups/day of caffeinated coffee compared to women who reported drinking none (HR = 1.81, 95% CI: 1.10-2.95). Decaffeinated coffee, total coffee, and caffeine were not statistically significantly associated with ovarian cancer incidence. Our results suggest that a component of coffee other than caffeine, or in combination with caffeine, may be associated with increased risk of ovarian cancer in postmenopausal women who drink five or more cups of coffee a day.
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Cafeína/efectos adversos , Estimulantes del Sistema Nervioso Central/efectos adversos , Café/efectos adversos , Neoplasias Ováricas/epidemiología , Programa de VERF , Anciano , Carcinoma/epidemiología , Estudios de Cohortes , Intervalos de Confianza , Demografía , Conducta de Ingestión de Líquido , Educación , Femenino , Humanos , Incidencia , Iowa/epidemiología , Estilo de Vida , Menstruación , Persona de Mediana Edad , Embarazo , Modelos de Riesgos Proporcionales , Estudios Prospectivos , Historia Reproductiva , Factores de Riesgo , Encuestas y CuestionariosRESUMEN
Detailed knowledge of the pathways by which ghrelin and leptin signal to AMPK in hypothalamic neurons and lead to regulation of appetite and glucose homeostasis is central to the development of effective means to combat obesity. Here we identify CaMKK2 as a component of one of these pathways, show that it regulates hypothalamic production of the orexigenic hormone NPY, provide evidence that it functions as an AMPKalpha kinase in the hypothalamus, and demonstrate that it forms a unique signaling complex with AMPKalpha and beta. Acute pharmacologic inhibition of CaMKK2 in wild-type mice, but not CaMKK2 null mice, inhibits appetite and promotes weight loss consistent with decreased NPY and AgRP mRNAs. Moreover, the loss of CaMKK2 protects mice from high-fat diet-induced obesity, insulin resistance, and glucose intolerance. These data underscore the potential of targeting CaMKK2 as a therapeutic intervention.
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Regulación del Apetito/fisiología , Quinasa de la Proteína Quinasa Dependiente de Calcio-Calmodulina/fisiología , Metabolismo Energético/fisiología , Hipotálamo/enzimología , Resistencia a la Insulina/fisiología , Quinasas de la Proteína-Quinasa Activada por el AMP , Acetil-CoA Carboxilasa/metabolismo , Proteína Relacionada con Agouti/genética , Proteína Relacionada con Agouti/metabolismo , Animales , Bencimidazoles/farmacología , Células Cultivadas , Dieta Aterogénica , Femenino , Intolerancia a la Glucosa/etiología , Prueba de Tolerancia a la Glucosa , Hipotálamo/patología , Immunoblotting , Técnicas para Inmunoenzimas , Inmunoprecipitación , Hibridación in Situ , Insulina/metabolismo , Integrasas/metabolismo , Masculino , Ratones , Ratones Endogámicos C57BL , Ratones Noqueados , Naftalimidas/farmacología , Neuropéptido Y/metabolismo , Proteínas Quinasas/metabolismo , ARN Mensajero/genética , ARN Mensajero/metabolismo , Transfección , Pérdida de PesoRESUMEN
Intervention trials with supplemental beta-carotene have observed either no effect or a harmful effect on lung cancer risk. Because food composition databases for specific carotenoids have only become available recently, epidemiological evidence relating usual dietary levels of these carotenoids with lung cancer risk is limited. We analyzed the association between lung cancer risk and intakes of specific carotenoids using the primary data from seven cohort studies in North America and Europe. Carotenoid intakes were estimated from dietary questionnaires administered at baseline in each study. We calculated study-specific multivariate relative risks (RRs) and combined these using a random-effects model. The multivariate models included smoking history and other potential risk factors. During follow-up of up to 7-16 years across studies, 3,155 incident lung cancer cases were diagnosed among 399,765 participants. beta-Carotene intake was not associated with lung cancer risk (pooled multivariate RR = 0.98; 95% confidence interval, 0.87-1.11; highest versus lowest quintile). The RRs for alpha-carotene, lutein/zeaxanthin, and lycopene were also close to unity. beta-Cryptoxanthin intake was inversely associated with lung cancer risk (RR = 0.76; 95% confidence interval, 0.67-0.86; highest versus lowest quintile). These results did not change after adjustment for intakes of vitamin C (with or without supplements), folate (with or without supplements), and other carotenoids and multivitamin use. The associations generally were similar among never, past, or current smokers and by histological type. Although smoking is the strongest risk factor for lung cancer, greater intake of foods high in beta-cryptoxanthin, such as citrus fruit, may modestly lower the risk.