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OBJECTIVE: Obesity is a metabolic disease. However, the underlying molecular mechanisms linking metabolic profiles and weight gain are largely unknown. METHODS: Here, we used semi-targeted metabolomics to assay 156 metabolites selected from 25 key metabolic pathways in plasma samples from 300 non-smoking healthy women identified from Mano-A-Mano, the Mexican American Cohort study. The study subjects were randomly divided into two cohorts: training (N = 200) and testing (N = 100) cohorts. Linear regression and Cox proportional hazard regression were used to assess the effect of body mass index (BMI) at baseline on metabolite levels and the effects of metabolites on significant weight gain during a 5-year follow-up. RESULTS: At baseline, we observed 7 metabolites significantly associated with BMI in both training and testing cohorts. They were Methyl succinate, Asparagine, Urate, Kynurenic acid, Glycine, Glutamic acid, and Serine. In further analysis, we identified 6 metabolites whose levels at baseline predicted significant weight gain during 5-year follow-up in both cohorts. They were Acetylcholine, Leucine, Hippuric acid, Acetylglycine, Urate, and Xanthine. CONCLUSIONS: The findings establish the baseline metabolic profiles for BMI, and suggest new metabolic targets for researchers attempting to understand the molecular mechanisms of weight gain and obesity.
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BACKGROUND: Flavonoids, polyphenolic compounds concentrated in fruits and vegetables, have experimentally demonstrated chemopreventive effects against oesophageal and gastric cancer. Few epidemiologic studies have examined flavonoid intake and incidence of these cancers, and none have considered survival. METHODS: In this USA multicentre population-based study, case participants (diagnosed during 1993-1995 with oesophageal adenocarcinoma (OEA, n=274), gastric cardia adenocarcinoma (GCA, n=248), oesophageal squamous cell carcinoma (OES, n=191), and other gastric adenocarcinoma (OGA, n=341)) and frequency-matched controls (n=662) were interviewed. Food frequency questionnaire responses were linked with USDA Flavonoid Databases and available literature for six flavonoid classes and lignans. Case participants were followed until 2000 for vital status. Multivariable-adjusted odds ratios (ORs) and hazard ratios (HRs) (95% confidence intervals (CIs)) were estimated, comparing highest with lowest intake quartiles, using polytomous logistic and proportional hazards regressions, respectively. RESULTS: Little or no consistent association was found for total flavonoid intake (main population sources: black tea, orange/grapefruit juice, and wine) and incidence or survival for any tumour type. Intake of anthocyanidins, common in wine and fruit juice, was associated with a 57% reduction in the risk of incident OEA (OR=0.43, 95% CI=0.29-0.66) and OES (OR=0.43, 95% CI=0.26-0.70). The ORs for isoflavones, for which coffee was the main source, were increased for all tumours, except OES. Anthocyanidins were associated with decreased risk of mortality for GCA (HR=0.63, 95% CI=0.42-0.95) and modestly for OEA (HR=0.87, 95% CI=0.60-1.26), but CIs were wide. CONCLUSIONS: Our findings, if confirmed, suggest that increased dietary anthocyanidin intake may reduce incidence and improve survival for these cancers.
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Dieta/estadística & datos numéricos , Neoplasias Esofágicas/epidemiología , Flavonoides/administración & dosificación , Neoplasias Gástricas/epidemiología , Estudios de Casos y Controles , Femenino , Frutas , Humanos , Incidencia , Masculino , Factores de Riesgo , Análisis de Supervivencia , Estados Unidos , VerdurasRESUMEN
BACKGROUND: The chromosome 9p21.3 region has been implicated in the pathogenesis of multiple cancers. METHODS: We systematically examined up to 203 tagging SNPs of 22 genes on 9p21.3 (19.9-32.8 Mb) in eight case-control studies: thyroid cancer, endometrial cancer (EC), renal cell carcinoma, colorectal cancer (CRC), colorectal adenoma (CA), oesophageal squamous cell carcinoma (ESCC), gastric cardia adenocarcinoma and osteosarcoma (OS). We used logistic regression to perform single SNP analyses for each study separately, adjusting for study-specific covariates. We combined SNP results across studies by fixed-effect meta-analyses and a newly developed subset-based statistical approach (ASSET). Gene-based P-values were obtained by the minP method using the Adaptive Rank Truncated Product program. We adjusted for multiple comparisons by Bonferroni correction. RESULTS: Rs3731239 in cyclin-dependent kinase inhibitors 2A (CDKN2A) was significantly associated with ESCC (P=7 × 10(-6)). The CDKN2A-ESCC association was further supported by gene-based analyses (Pgene=0.0001). In the meta-analyses by ASSET, four SNPs (rs3731239 in CDKN2A, rs615552 and rs573687 in CDKN2B and rs564398 in CDKN2BAS) showed significant associations with ESCC and EC (P<2.46 × 10(-4)). One SNP in MTAP (methylthioadenosine phosphorylase) (rs7023329) that was previously associated with melanoma and nevi in multiple genome-wide association studies was associated with CRC, CA and OS by ASSET (P=0.007). CONCLUSION: Our data indicate that genetic variants in CDKN2A, and possibly nearby genes, may be associated with ESCC and several other tumours, further highlighting the importance of 9p21.3 genetic variants in carcinogenesis.
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Biomarcadores de Tumor/genética , Cromosomas Humanos Par 9/genética , Inhibidor p15 de las Quinasas Dependientes de la Ciclina/genética , Inhibidor p16 de la Quinasa Dependiente de Ciclina/genética , Neoplasias/genética , Polimorfismo de Nucleótido Simple/genética , Estudios de Casos y Controles , Predisposición Genética a la Enfermedad , Humanos , Metaanálisis como Asunto , PronósticoRESUMEN
BACKGROUND: Dietary glycemic index (GI) and glycemic load (GL) typically have a positive relationship with obesity and diabetes, which are risk factors for liver cancer. However, studies on their association with liver cancer have yielded inconsistent results. Therefore, we assessed the association of GI, GL, and carbohydrates with liver cancer risk. PATIENTS AND METHODS: A total of 72 966 women and 60 207 men from the Shanghai Women's Health Study (SWHS) and the Shanghai Men's Health Study (SMHS) were included for analysis. Food frequency questionnaire (FFQ) data were used to calculate daily dietary GI, GL, and carbohydrate intake. These values were energy adjusted and categorized into quintiles. The hazard ratios (HRs) and 95% confidence intervals (CI) were calculated with adjustment for potential confounders. RESULTS: After a median follow-up time of 11.2 years for the SWHS and 5.3 years for the SMHS, 139 and 208 incident liver cancer cases were identified in the SWHS and SMHS, respectively. In multivariable Cox regression models, no statistically significant trends by quintile of GI, GL, or carbohydrate intake were observed. Stratification by chronic liver disease/hepatitis, diabetes, or body mass index (BMI) did not alter the findings. CONCLUSIONS: There is little evidence that dietary GI, GL, or carbohydrates affect the incidence of liver cancer in this Asian population.
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Carbohidratos de la Dieta/administración & dosificación , Glucosa/administración & dosificación , Índice Glucémico , Neoplasias Hepáticas/etiología , Adulto , China , Femenino , Humanos , Masculino , Persona de Mediana Edad , Factores de RiesgoRESUMEN
Array comparative genomic hybridization was used to identify copy number alterations in clear cell renal cell carcinoma (ccRCC) patient tumors to identify associations with patient/clinical characteristics. Of 763 ccRCC patients, 412 (54%) provided frozen biopsies. Clones were analyzed for significant copy number differences, adjusting for multiple comparisons and covariates in multivariate analyses. Frequent alterations included losses on: 3p (92.2%), 14q (46.8%), 8p (38.1%), 4q (35.4%), 9p (32.3%), 9q (31.8%), 6q (30.8%), 3q (29.4%), 10q (25.7%), 13q (24.5%), 1p (23.5%) and gains on 5q (60.2%), 7q (39.6%), 7p (30.6%), 5p (26.5%), 20q (25.5%), 12q (24.8%), 12p (22.8%). Stage and grade were associated with 1p, 9p, 9q, 13q and 14q loss and 12q gain. Males had more alterations compared with females, independent of stage and grade. Significant differences in the number/types of alterations were observed by family cancer history, age at diagnosis and smoking status. Von Hippel-Lindau (VHL) gene inactivation was associated with 3p loss (P
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BACKGROUND: Recent data suggest a link between blood leukocyte DNA methylation, and cancer risk. However, reports on DNA methylation from a prospective study are unavailable for gastric cancer. METHODS: We explored the association between methylation in pre-diagnostic blood leukocyte DNA and gastric cancer risk in a case-control study nested in the prospective Shanghai Women's Health Study cohort. Incident gastric cancer cases (n=192) and matched controls (n=384) were included in the study. Methylation of Alu and long interspersed nucleotide elements (LINE)-1 were evaluated using bisulphite pyrosequencing. Odds ratios (ORs) and 95% confidence intervals (CI) were calculated from logistic regression adjusting for potential confounders. RESULTS: Alu methylation was inversely associated with gastric cancer risk, mainly among cases diagnosed one or more years after blood collection. After excluding cases diagnosed during the first year of follow-up, the ORs for the third, second, and first quartiles of Alu methylation compared with the highest quartile were 2.43 (1.43-4.13), 1.47(0.85-2.57), and 2.22 (1.28-3.84), respectively. This association appeared to be modified by dietary intake, particularly isoflavone. In contrast, LINE-1 methylation levels were not associated with gastric cancer risk. CONCLUSION: Evidence from this prospective study is consistent with the hypothesis that DNA hypomethylation in blood leukocytes may be related to cancer risk, including risk of gastric cancer.
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Elementos Alu , Leucocitos/metabolismo , Elementos de Nucleótido Esparcido Largo , Neoplasias Gástricas/epidemiología , Adulto , Anciano , Elementos Alu/genética , Estudios de Casos y Controles , China/epidemiología , Metilación de ADN , ADN de Neoplasias/análisis , ADN de Neoplasias/metabolismo , Femenino , Promoción de la Salud , Humanos , Elementos de Nucleótido Esparcido Largo/genética , Persona de Mediana Edad , Estudios Prospectivos , Sistema de Registros , Factores de Riesgo , Neoplasias Gástricas/sangre , Salud de la MujerRESUMEN
BACKGROUND: There are few known risk factors for renal cell carcinoma (RCC). Two small hospital-based case-control studies suggested an association between short blood telomere length (TL) and increased RCC risk. METHODS: We conducted a large population-based case-control study in two metropolitan regions of the United States comparing relative TL in DNA derived from peripheral blood samples from 891 RCC cases and 894 controls. Odds ratios and 95% confidence intervals were estimated using unconditional logistic regression in both unadjusted and adjusted models. RESULTS: Median TL was 0.85 for both cases and controls (P=0.40), and no differences in RCC risk by quartiles of TL were observed. Results of analyses stratified by age, sex, race, tumour stage, and time from RCC diagnosis to blood collection were similarly null. In multivariate analyses among controls, increasing age and history of hypertension were associated with shorter TL (P<0.001 and P=0.07, respectively), and African Americans had longer TL than Caucasians (P<0.001). CONCLUSION: These data do not support the hypothesis that blood TL is associated with RCC. This population-based case-control study is, to our knowledge, the largest investigation to date of TL and RCC.
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Carcinoma de Células Renales/sangre , Carcinoma de Células Renales/genética , Neoplasias Renales/sangre , Neoplasias Renales/genética , Telómero/genética , Adolescente , Adulto , Factores de Edad , Anciano , Anciano de 80 o más Años , Estudios de Casos y Controles , Niño , Preescolar , Femenino , Humanos , Hipertensión/genética , Lactante , Recién Nacido , Masculino , Persona de Mediana Edad , Análisis Multivariante , Factores de Riesgo , Estados Unidos , Adulto JovenRESUMEN
BACKGROUND: High-temperature cooked meat contains two families of carcinogens, heterocyclic amines (HCAs) and polycyclic aromatic hydrocarbons (PAHs). Given the kidneys' role in metabolism and urinary excretion of these compounds, we investigated meat-derived mutagens, as well as meat intake and cooking methods, in a population-based case-control study conducted in metropolitan Detroit and Chicago. METHODS: Newly diagnosed, histologically confirmed adenocarcinoma of the renal parenchyma (renal cell carcinoma (RCC)) cases (n=1192) were frequency matched on age, sex, and race to controls (n=1175). The interviewer-administered Diet History Questionnaire (DHQ) included queries for meat-cooking methods and doneness with photographic aids. Levels of meat mutagens were estimated using the DHQ in conjunction with the CHARRED database. RESULTS: The risk of RCC increased with intake of barbecued meat (P(trend)=0.04) and the PAH, benzo(a)pyrene (BaP) (multivariable-adjusted odds ratio and 95% confidence interval, highest vs lowest quartile: 1.50 (1.14, 1.95), P(trend)=0.001). With increasing BaP intake, the risk of RCC was more than twofold in African Americans and current smokers (P(interaction)<0.05). We found no association for HCAs or overall meat intake. CONCLUSION: BaP intake, a PAH in barbecued meat, was positively associated with RCC. These biologically plausible findings advocate further epidemiological investigation into dietary intake of BaP and risk of RCC.
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Adenocarcinoma/etiología , Carcinoma de Células Renales/etiología , Culinaria , Neoplasias Renales/etiología , Carne/efectos adversos , Mutágenos/efectos adversos , Adenocarcinoma/epidemiología , Adulto , Anciano , Carcinoma de Células Renales/epidemiología , Estudios de Casos y Controles , Chicago/epidemiología , Femenino , Estudios de Seguimiento , Humanos , Neoplasias Renales/epidemiología , Persona de Mediana Edad , Pronóstico , Factores de Riesgo , Tasa de Supervivencia , Adulto JovenRESUMEN
BACKGROUND: The influence of different types and intensities of physical activity on risk for breast cancer is unclear. METHODS: In a prospective cohort of 73,049 Chinese women (40-70 years), who had worked outside the home, we studied breast cancer risk in relation to specific types of self-reported and work history-related physical activity, including adolescent and adult exercise and household activity and walking and cycling for transportation. Occupational sitting time and physical activity energy expenditure were assigned based on lifetime occupational histories. RESULTS: In all, 717 incident breast cancer cases were diagnosed. Breast cancer risk was lower for women in the lowest quartile of average occupational sitting time and in the highest quartile of average occupational energy expenditure (adjusted hazard ratio (HR): 0.81 and 0.73, respectively, P ≤ 0.05). Adult exercise at or above the recommended level (8 metabolic equivalent (MET) h per week per year) was associated with lower risk (adjusted HR: 0.73, P<0.05) in post-menopausal women. Analysis of joint effects showed that having both an active job and exercise participation did not confer an additional benefit. Other common daily activities were not associated with lower risk. INTERPRETATION: These findings suggest that both exercise and occupational activity are associated with lower breast cancer risk, which supports current health promotion campaigns promoting exercise.
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Actividad Motora , Adulto , Anciano , Pueblo Asiatico , Neoplasias de la Mama , Metabolismo Energético , Femenino , Humanos , Incidencia , Persona de Mediana Edad , Ocupaciones , Estudios Prospectivos , Conducta Sedentaria , CaminataRESUMEN
Deoxynivalenol (DON) is a trichothecene mycotoxin found on wheat, maize and barley. In ecological surveys in China, DON and other trichothecenes have been implicated in acute poisoning episodes and linked with the incidence of esophageal cancer. In order to better understand exposure patterns, this pilot survey provided a combined measure of urinary un-metabolised or free DON (fD) and its glucuronide metabolite (DG) in a subset of 60 samples taken from the Shanghai Women's Health Study cohort, China. Samples were collected in 1997/1998 from women age 40-70 years. Urinary fD+DG combined was detected in 58/60 (96.7%) samples (mean 5.9 ng DON/mg creatinine; range nd-30.5); a similar frequency, and a mean level approximately half, of that previously observed for women in the UK. Wheat consumption was approximately 25% of that consumed by western diets; thus DON contamination of wheat may be higher in Shanghai than the UK. The de-epoxy metabolite of DON, a detoxification product observed in animals, was not detected, suggesting that humans may be particularly sensitive to DON due to a more restricted detoxification capacity.
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Micotoxinas/orina , Tricotecenos/orina , Adulto , Anciano , Biomarcadores , China , Demografía , Exposición a Riesgos Ambientales , Femenino , Contaminación de Alimentos , Humanos , Persona de Mediana Edad , Vigilancia de la PoblaciónRESUMEN
BACKGROUND: Occupational exposures to dusts have generally been examined in relation to cancers of the respiratory system and have rarely been examined in relation to other cancers, such as renal cell carcinoma (RCC). Although previous epidemiological studies, though few, have shown certain dusts, such as asbestos, to increase renal cancer risk, the potential for other occupational dust exposures to cause kidney damage and/or cancer may exist. We investigated whether asbestos, as well as 20 other occupational dust exposures, were associated with RCC risk in a large European, multi-center, hospital-based renal case-control study. METHODS: General occupational histories and job-specific questionnaires were reviewed by occupational hygienists for subject-specific information. Odds ratios (ORs) and 95% confidence intervals (95% CIs) between RCC risk and exposures were calculated using unconditional logistic regression. RESULTS: Among participants ever exposed to dusts, significant associations were observed for glass fibres (OR: 2.1; 95% CI: 1.1-3.9), mineral wool fibres (OR: 2.5; 95% CI: 1.2-5.1), and brick dust (OR: 1.5; 95% CI: 1.0-2.4). Significant trends were also observed with exposure duration and cumulative exposure. No association between RCC risk and asbestos exposure was observed. CONCLUSION: Results suggest that increased RCC risk may be associated with occupational exposure to specific types of dusts. Additional studies are needed to replicate and extend findings.
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Carcinoma de Células Renales/epidemiología , Polvo , Neoplasias Renales/epidemiología , Enfermedades Profesionales/epidemiología , Exposición Profesional/efectos adversos , Anciano , Amianto/toxicidad , Carcinógenos , Estudios de Casos y Controles , Europa (Continente) , Europa Oriental , Femenino , Vidrio , Humanos , Masculino , Persona de Mediana Edad , Fibras Minerales , Enfermedades Profesionales/etiología , Medición de RiesgoRESUMEN
BACKGROUND: Circulating pepsinogens can indicate atrophic gastritis, a precursor of gastric cancer. We tested the association between gastric cancer and plasma pepsinogens and antibodies against Helicobacter pylori in a case-control study nested in a prospective cohort. METHODS: We selected 141 gastric cancer cases and 282 incidence-density sampled controls. Plasma concentrations of pepsinogens 1 and 2 were measured using ELISA kits, and anti-H. pylori antibodies were measured using a kit specific to Chinese strains. Associations were estimated using conditional logistic regression models adjusted for potential confounders. RESULTS: Gastric cancer subjects were more likely to be anti-H. pylori positive than controls, 97 vs 92%. A plasma pepsinogen 1 (PG1) concentration <50 ng ml(-1) (15% of cases) was associated with a significantly increased risk of gastric cancer (OR 4.23; (95% CI: 1.86-9.63), whereas a plasma pepsinogen 2 (PG2) concentration >6.6 ng ml(-1) (75% of cases) was also associated with a significantly increased risk of gastric cancer (OR 3.62; (95% CI: 1.85-7.09). We also found that the PG1 : 2 ratio had a nearly linear association with gastric cancer risk. CONCLUSION: Lower plasma PG1 : 2 ratios are associated with a higher risk of gastric cancer. Furthermore, it appears that circulating pepsinogens 1 and 2 may be independently associated with the risk of gastric cancer.
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Anticuerpos Antibacterianos/sangre , Pueblo Asiatico/estadística & datos numéricos , Infecciones por Helicobacter/complicaciones , Helicobacter pylori/inmunología , Pepsinógenos/sangre , Neoplasias Gástricas/enzimología , Neoplasias Gástricas/microbiología , Adulto , Anciano , Biomarcadores de Tumor/sangre , Estudios de Casos y Controles , China/epidemiología , Estudios de Cohortes , Factores de Confusión Epidemiológicos , Femenino , Infecciones por Helicobacter/microbiología , Humanos , Modelos Lineales , Persona de Mediana Edad , Pepsinógeno A/sangre , Pepsinógeno C/sangre , Neoplasias Gástricas/epidemiología , Salud de la MujerRESUMEN
BACKGROUND: The effect of moderate to heavy drinking (>15 g per day) on renal cell cancer (RCC) risk is unclear. METHOD: The relationship between alcohol consumption and RCC was examined in the NIH-AARP Diet and Health Study (n=49 2187, 1814 cases). RESULTS: Compared with >0 to <5 g per day of alcohol consumption, the multivariate relative risk (95% confidence intervals) for 15 to <30 and î¶30 g per day was, 0.75 (0.63-0.90) and 0.71 (0.59-0.85), respectively, in men and 0.67 (0.42-1.07) and 0.43 (0.22-0.84), respectively, in women. CONCLUSION: Alcohol consumption was inversely associated with RCC in a dose-response manner. The inverse association may be extended to î¶30 g per day of alcohol intake.
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Consumo de Bebidas Alcohólicas/epidemiología , Carcinoma de Células Renales/epidemiología , Neoplasias Renales/epidemiología , Dieta , Femenino , Humanos , Masculino , Estudios Prospectivos , Factores de Riesgo , Encuestas y CuestionariosRESUMEN
BACKGROUND AND STUDY AIM: The establishment of precise and valid diagnostic criteria is important for any disease. We determined the interobserver reliability in the endoscopic diagnosis and grading of Barrett's esophagus. PATIENTS AND METHODS: Video clips of endoscopy in 21 patients with/without Barrett's esophagus were used for training (n = 3) and for diagnosis/grading (n = 18) of Barrett's esophagus by endoscopists from seven hospitals in Asia. Barrett's esophagus was graded using the Prague C & M Criteria whereby the circumferential extent of the Barrett's segment (C value), maximum extent of Barrett's segment (M value), location of the gastroesophageal junction, and location of the diaphragmatic hiatus were scored. The intraclass correlation coefficients (ICC) were calculated as a measure of interobserver reliability. RESULTS: A total of 34 endoscopists participated. ICC values for the scores of the C value, M value, location of the gastroesophageal junction, and location of the diaphragmatic hiatus were: 0.92 (95 % confidence interval [CI] 0.88 - 0.97), 0.94 (95 %CI 0.90 - 0.98), 0.86 (95 %CI 0.78 - 0.94), and 0.81 (95 %CI 0.71 - 0.92), respectively, indicating excellent interobserver agreement. The differences in region/country, endoscopists' experience, case volume of participating centers, or primary practice type had no significant effect on the reliability. The ICC values for recognition of Barrett's esophagus of > or = 1 cm were 0.90 (95 %CI 0.80 - 1.00) and 0.92 (95 %CI 0.87 - 0.98) for the C and M values, respectively, whereas the corresponding ICC values for Barrett's segment of < 1 cm were 0.18 (95 %CI 0.03 - 0.32) and 0.21 (95 %CI 0.00 - 0.51), respectively. CONCLUSIONS: Despite the uncommon occurrence of Barrett's esophagus in Asia, our endoscopists exhibited excellent agreement in the endoscopic diagnosis and grading of Barrett's esophagus using the Prague C & M Criteria. However, in view of the low interobserver reliability in recognizing Barrett's segments of < 1 cm, future studies in Asia should take this into account when selecting the study population.
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Esófago de Barrett/patología , Competencia Clínica/estadística & datos numéricos , Esofagoscopía/normas , Asia , Esófago de Barrett/diagnóstico , Humanos , Variaciones Dependientes del Observador , Reproducibilidad de los ResultadosRESUMEN
BACKGROUND: The association between renal cell carcinoma (RCC) risk and family history of cancer has not been examined with an adequate number of African Americans (AAs). METHODS: In a population-based case-control study, unconditional logistic regression was used to calculate the association between RCC risk and a family history of cancer among 1217 RCC cases and 1235 controls. RESULTS: Increased RCC risk was shown for subjects with at least one first-degree relative with kidney cancer (odds ratio=2.29; 95% confidence interval=1.31-4.00). No differences in risk were observed when analyses were stratified by race. For Caucasians, excess risk was observed among those reporting a sibling with kidney cancer, whereas for AAs, increased risk occurred among subjects reporting either a sibling or parent affected with the disease. A family history of non-renal cancers, and those related to smoking or to the von Hippel-Lindau syndrome, revealed no association with RCC risk. CONCLUSION: The RCC risk associated with a family history of kidney cancer is similar among Caucasians and AAs.
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Negro o Afroamericano , Carcinoma de Células Renales/etiología , Salud de la Familia , Neoplasias Renales/etiología , Neoplasias/etiología , Población Blanca , Adulto , Negro o Afroamericano/estadística & datos numéricos , Anciano , Carcinoma de Células Renales/epidemiología , Carcinoma de Células Renales/etnología , Carcinoma de Células Renales/genética , Estudios de Casos y Controles , Femenino , Predisposición Genética a la Enfermedad , Humanos , Neoplasias Renales/epidemiología , Neoplasias Renales/etnología , Neoplasias Renales/genética , Masculino , Persona de Mediana Edad , Neoplasias/epidemiología , Neoplasias/etnología , Neoplasias/genética , Factores de Riesgo , Población Blanca/estadística & datos numéricos , Adulto JovenRESUMEN
Renal-cell carcinomas (RCC) are frequent in central and eastern Europe and the reasons remain unclear. Molecular mechanisms, except for VHL, have not been much investigated. We analysed 361 RCCs (334 clear-cell carcinomas) from a multi-centre case-control study for mutations in TP53 (exons 5-9 in the whole series and exons 4 and 10 in a pilot subset of 60 tumours) and a pilot 50 tumours for mutations in EGFR (exons 18-21) or KRAS (codon 12) in relation to VHL status. TP53 mutations were detected in 4% of clear-cell cases, independently of VHL mutations. In non-clear-cell carcinomas, they were detected in 11% of VHL-wild-type tumours and in 0% of tumours with VHL functional mutations. No mutations were found in EGFR or KRAS. We conclude that mutations in TP53, KRAS, or EGFR are not major contributors to the RCC development even in the absence of VHL inactivation. The prevalence of TP53 mutations in relation to VHL status may differ between clear-cell and other renal carcinomas.
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Carcinoma de Células Renales/genética , Genes erbB-1 , Genes p53 , Genes ras , Neoplasias Renales/genética , Mutación , Adulto , Anciano , Anciano de 80 o más Años , Carcinoma de Células Renales/patología , Estudios de Casos y Controles , Europa (Continente) , Femenino , Silenciador del Gen , Humanos , Neoplasias Renales/patología , Estilo de Vida , Masculino , Persona de Mediana Edad , Factores de Riesgo , Células Tumorales CultivadasRESUMEN
Mediated by binding to the high-affinity vitamin D receptor (VDR), vitamin D forms a heterodimer complex with the retinoid-X-receptor (RXR). Variation in both genes has been shown to modify renal cell carcinoma (RCC) risk. Therefore, we investigated whether VDR and RXRA polymorphisms modify associations between RCC risk and frequency of dietary intake of vitamin D and calcium rich foods, and occupational ultraviolet exposure among 777 RCC case and 1035 controls from Central and Eastern Europe. A positive association was observed in this population between increasing dietary intake frequency of yogurt, while an inverse association was observed with egg intake frequency. RXRA polymorphisms, located 3' of the coding sequence, modified associations between specific vitamin D rich foods and RCC risk, while RXRA polymorphisms, located in introns 1 and 4, modified associations with specific calcium rich foods. Results suggest that variants in the RXRA gene modified the associations observed between RCC risk and calcium and vitamin D intake.
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OBJECTIVE: Central and Eastern Europe has among the highest rates of renal cell cancer worldwide. Few studies have been conducted in these areas to investigate the possible role of occupational exposures in renal cell cancer aetiology. The purpose of this study was to examine the association of renal cell cancer with employment in specific occupations and industries. METHODS: From 1999 to 2003, we conducted a hospital-based case-control study in seven areas of the Czech Republic, Poland, Romania and Russia. A detailed occupational history was collected from renal cell cancer cases and controls, together with information on potential confounders. Odds ratios (ORs) and 95% CI of cancer risk were calculated for having ever been employed in selected jobs and industries, with follow-up analyses examining duration of employment. RESULTS: A total of 992 histologically confirmed incident renal cell cancer cases and 1459 controls were included in the analysis. An increased risk of renal cell cancer was observed for workers in agricultural labour and animal husbandry (OR 1.43; 95% CI 1.05 to 1.93), particularly among women employed as general farm workers (OR 2.73; 95% CI 1.05 to 7.13). Risk gradients for agricultural work increased with longer employment. An overall increased risk of renal cell cancer was seen among architects and engineers (OR 1.89; 95% CI 1.35 to 2.65), and mechanical engineers (OR 1.71; 95% CI 1.03 to 2.84). CONCLUSIONS: Our data suggest an association between renal cell cancer and agricultural work, particularly among female workers.
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Carcinoma de Células Renales/epidemiología , Neoplasias Renales/epidemiología , Enfermedades Profesionales/epidemiología , Ocupaciones/estadística & datos numéricos , Adulto , Anciano , Anciano de 80 o más Años , Agricultura/estadística & datos numéricos , Arquitectura/estadística & datos numéricos , Estudios de Casos y Controles , República Checa/epidemiología , Ingeniería/estadística & datos numéricos , Femenino , Humanos , Masculino , Persona de Mediana Edad , Polonia/epidemiología , Factores de Riesgo , Rumanía/epidemiología , Federación de Rusia/epidemiología , Factores Sexuales , Factores de TiempoRESUMEN
We report a patient with isolated left ventricular non-compaction diagnosed by echocardiography and cardiac magnetic resonance imaging. She developed refractory congestive heart failure and subsequently underwent successful heart transplantation. This type of cardiomyopathy is thought to be caused by the arrest of normal embryogenesis of the endocardium and myocardium. The spectrum of clinical, radiological, and pathological abnormalities is discussed.
Asunto(s)
Cardiomiopatía Hipertrófica/terapia , Trasplante de Corazón , Disfunción Ventricular Izquierda/terapia , Adulto , Cardiomiopatía Hipertrófica/complicaciones , Cardiomiopatía Hipertrófica/diagnóstico , Ecocardiografía/métodos , Femenino , Insuficiencia Cardíaca/etiología , Insuficiencia Cardíaca/terapia , Humanos , Imagen por Resonancia Magnética/métodos , Disfunción Ventricular Izquierda/complicaciones , Disfunción Ventricular Izquierda/diagnósticoRESUMEN
BACKGROUND: In the United States, the rates and temporal trends of oesophageal cancer overall and for the two predominant histologic types - adenocarcinoma (ADC) and squamous cell carcinoma (SCC) - differ between Blacks and Whites, but little is known with regard to the patterns among Asians/Pacific Islanders or Hispanics. METHODS: Using the Surveillance, Epidemiology, and End Results programme data, we analysed oesophageal cancer incidence patterns by race, sex, and histologic type for the period 1977-2005. RESULTS: Total oesophageal cancer incidence has been increasing among Whites only; the rates among all other race groups have declined. Moreover, rates among White men surpassed those among Blacks in 2004. Oesophageal SCC rates have been decreasing among virtually all racial/ethnic groups; rates among Hispanic and Asian/Pacific Islander men have been intermediate to those of Blacks and Whites, with rates among women being lower than those among Blacks or Whites. The ADC rates among Hispanic men may be rising, akin to the historical trends among Whites and Blacks. The sex ratios for these cancers also varied markedly. CONCLUSIONS: These observations may provide clues for aetiological research.