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BACKGROUND: Exposure to ambient air pollution is associated with a significant number of deaths. Much of the evidence associating air pollution with adverse effects is from North American and Europe, partially due to incomplete data in other regions limiting location specific examinations. The aim of the current paper is to leverage satellite derived air quality data to examine the relationship between ambient particulate matter and all-cause and cause-specific mortality in Asia. METHODS: Six cohorts from the Asia Cohort Consortium provided residential information for participants, recruited between 1991 and 2008, across six countries (Bangladesh, India, Iran, Japan, South Korea, and Taiwan). Ambient particulate material (PM2·5) levels for the year of enrolment (or 1998 if enrolled earlier) were assigned utilizing satellite and sensor-based maps. Cox proportional models were used to examine the association between ambient air pollution and all-cause and cause-specific mortality (all cancer, lung cancer, cardiovascular and lung disease). Models were additionally adjusted for urbanicity (representing urban and built characteristics) and stratified by smoking status in secondary analyses. Country-specific findings were pooled via random-effects meta-analysis. FINDINGS: More than 300,000 participants across six cohorts were included, representing more than 4-million-person years. A positive relationship was observed between a 5 µg/m (Dockery et al., 1993) increase in PM2·5 and cardiovascular mortality (HR: 1·06, 95 % CI: 0.99, 1·13). The additional adjustment for urbanicity resulted in increased associations between PM2.5 and mortality outcomes, including all-cause mortality (1·04, 95 % CI: 0·97, 1·11). Results were generally similar regardless of whether one was a current, never, or ex-smoker. INTERPRETATION: Using satellite and remote sensing technology we showed that associations between PM2.5 and all-cause and cause-specific Hazard Ratios estimated are similar to those reported for U.S. and European cohorts. FUNDING: This project was supported by the Health Effects Institute. Grant number #4963-RFA/18-5. Specific funding support for individual cohorts is described in the Acknowledgements.
Assuntos
Poluentes Atmosféricos , Poluição do Ar , Exposição Ambiental , Material Particulado , Humanos , Material Particulado/análise , Ásia , Exposição Ambiental/estatística & dados numéricos , Exposição Ambiental/efeitos adversos , Masculino , Estudos de Coortes , Feminino , Poluição do Ar/estatística & dados numéricos , Poluição do Ar/efeitos adversos , Poluentes Atmosféricos/análise , Pessoa de Meia-Idade , Adulto , Doenças Cardiovasculares/mortalidade , Idoso , Neoplasias/mortalidade , Neoplasias Pulmonares/mortalidade , Pneumopatias/mortalidade , Modelos de Riscos Proporcionais , Causas de MorteRESUMO
BACKGROUND: Diesel engine exhaust (DEE) exposure causes lung cancer, but the molecular mechanisms by which this occurs are not well understood. OBJECTIVES: To assess transcriptomic alterations in nasal epithelium of DEE-exposed factory workers to better understand the cellular and molecular effects of DEE. METHODS: Nasal epithelial brushings were obtained from 41 diesel engine factory workers exposed to relatively high levels of DEE (17.2-105.4 µg/m3), and 38 unexposed workers from factories without DEE exposure. mRNA was profiled for gene expression using Affymetrix microarrays. Linear modeling was used to identify differentially expressed genes associated with DEE exposure and interaction effects with current smoking status. Pathway enrichment among differentially expressed genes was assessed using EnrichR. Gene Set Enrichment Analysis (GSEA) was used to compare gene expression patterns between datasets. RESULTS: 225 genes had expression associated with DEE exposure after adjusting for smoking status (FDR q < 0.25) and were enriched for genes in pathways related to oxidative stress response, cell cycle pathways such as MAPK/ERK, protein modification, and transmembrane transport. Genes up-regulated in DEE-exposed individuals were enriched among the genes most up-regulated by cigarette smoking in a previously reported bronchial airway smoking dataset. We also found that the DEE signature was enriched among the genes most altered in two previous studies of the effects of acute DEE on PBMC gene expression. An exposure-response relationship was demonstrated between air levels of elemental carbon and the first principal component of the DEE signature. CONCLUSIONS: A gene expression signature was identified for workers occupationally exposed to DEE that was altered in an exposure-dependent manner and had some overlap with the effects of smoking and the effects of acute DEE exposure. This is the first study of gene expression in nasal epithelial cells of workers heavily exposed to DEE and provides new insights into the molecular alterations that occur with DEE exposure.
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Mucosa Nasal , Exposição Ocupacional , Transcriptoma , Emissões de Veículos , Humanos , Leucócitos Mononucleares , Mucosa Nasal/efeitos dos fármacos , Emissões de Veículos/toxicidadeRESUMO
Background: There is observational evidence suggesting that high vitamin D concentrations may protect against lung cancer. To investigate this hypothesis in detail, we measured circulating vitamin D concentrations in prediagnostic blood from 20 cohorts participating in the Lung Cancer Cohort Consortium (LC3). Patients and methods: The study included 5313 lung cancer cases and 5313 controls. Blood samples for the cases were collected, on average, 5 years before lung cancer diagnosis. Controls were individually matched to the cases by cohort, sex, age, race/ethnicity, date of blood collection, and smoking status in five categories. Liquid chromatography coupled with tandem mass spectrometry was used to separately analyze 25-hydroxyvitamin D2 [25(OH)D2] and 25-hydroxyvitamin D3 [25(OH)D3] and their concentrations were combined to give an overall measure of 25(OH)D. We used conditional logistic regression to calculate odds ratios (ORs) and 95% confidence intervals (CIs) for 25(OH)D as both continuous and categorical variables. Results: Overall, no apparent association between 25(OH)D and risk of lung cancer was observed (multivariable adjusted OR for a doubling in concentration: 0.98, 95% CI: 0.91, 1.06). Similarly, we found no clear evidence of interaction by cohort, sex, age, smoking status, or histology. Conclusion: This study did not support an association between vitamin D concentrations and lung cancer risk.
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Biomarcadores Tumorais/sangue , Carcinoma Pulmonar de Células não Pequenas/epidemiologia , Neoplasias Pulmonares/epidemiologia , Carcinoma de Pequenas Células do Pulmão/epidemiologia , Deficiência de Vitamina D/fisiopatologia , Vitamina D/sangue , Adenocarcinoma/sangue , Adenocarcinoma/epidemiologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Carcinoma de Células Grandes/sangue , Carcinoma de Células Grandes/epidemiologia , Carcinoma Pulmonar de Células não Pequenas/sangue , Carcinoma de Células Escamosas/sangue , Carcinoma de Células Escamosas/epidemiologia , Estudos de Casos e Controles , Feminino , Seguimentos , Saúde Global , Humanos , Neoplasias Pulmonares/sangue , Masculino , Pessoa de Meia-Idade , Prognóstico , Estudos Prospectivos , Fatores de Risco , Carcinoma de Pequenas Células do Pulmão/sangue , Vitaminas/sangue , Adulto JovemRESUMO
BACKGROUND: We adapted Bayesian statistical learning strategies to the prognosis field to investigate if genome-wide common SNP improve the prediction ability of clinico-pathological prognosticators and applied it to non-muscle invasive bladder cancer (NMIBC) patients. METHODS: Adapted Bayesian sequential threshold models in combination with LASSO were applied to consider the time-to-event and the censoring nature of data. We studied 822 NMIBC patients followed-up >10 years. The study outcomes were time-to-first-recurrence and time-to-progression. The predictive ability of the models including up to 171,304 SNP and/or 6 clinico-pathological prognosticators was evaluated using AUC-ROC and determination coefficient. RESULTS: Clinico-pathological prognosticators explained a larger proportion of the time-to-first-recurrence (3.1 %) and time-to-progression (5.4 %) phenotypic variances than SNPs (1 and 0.01 %, respectively). Adding SNPs to the clinico-pathological-parameters model slightly improved the prediction of time-to-first-recurrence (up to 4 %). The prediction of time-to-progression using both clinico-pathological prognosticators and SNP did not improve. Heritability (h (2)) of both outcomes was <1 % in NMIBC. CONCLUSIONS: We adapted a Bayesian statistical learning method to deal with a large number of parameters in prognostic studies. Common SNPs showed a limited role in predicting NMIBC outcomes yielding a very low heritability for both outcomes. We report for the first time a heritability estimate for a disease outcome. Our method can be extended to other disease models.
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Teorema de Bayes , Carcinoma de Células de Transição/patologia , Neoplasias da Bexiga Urinária/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Área Sob a Curva , Biomarcadores Tumorais/análise , Carcinoma de Células de Transição/genética , Progressão da Doença , Genótipo , Humanos , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/genética , Recidiva Local de Neoplasia/patologia , Polimorfismo de Nucleotídeo Único , Valor Preditivo dos Testes , Prognóstico , Curva ROC , Sensibilidade e Especificidade , Neoplasias da Bexiga Urinária/genéticaRESUMO
The Chinese national pollution census has indicated that the domestic burning of solid fuels is an important contributor to nitrogen dioxide (NO2 ) and sulfur dioxide (SO2 ) emissions in China. To characterize indoor NO2 and SO2 air concentrations in relation to solid fuel use and stove ventilation in the rural counties of Xuanwei and Fuyuan, in Yunnan Province, China, which have among the highest lung cancer rates in the nation, a total of 163 participants in 30 selected villages were enrolled. Indoor 24-h NO2 and SO2 samples were collected in each household over two consecutive days. Compared to smoky coal, smokeless coal use was associated with higher NO2 concentrations [geometric mean (GM) = 132 µg/m(3) for smokeless coal and 111 µg/m(3) for smoky coal, P = 0.065] and SO2 [limit of detection = 24 µg/m(3) ; percentage detected (%Detect) = 86% for smokeless coal and 40% for smoky coal, P < 0.001]. Among smoky coal users, significant variation of NO2 and SO2 air concentrations was observed across different stove designs and smoky coal sources in both counties. Model construction indicated that the measurements of both pollutants were influenced by stove design. This exposure assessment study has identified high levels of NO2 and SO2 as a result of burning solid fuels for cooking and heating.
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Poluição do Ar em Ambientes Fechados/análise , Culinária/métodos , Calefação/métodos , Dióxido de Nitrogênio/análise , Dióxido de Enxofre/análise , China , Combustíveis Fósseis/análise , Combustíveis Fósseis/toxicidade , Humanos , Neoplasias Pulmonares/etiologia , População Rural , Fumaça/análise , VentilaçãoRESUMO
Black carbon (BC) emissions from solid fuel combustion are associated with increased morbidity and mortality and are important drivers of climate change. We studied BC measurements, approximated by particulate matter (PM2.5 ) absorbance, in rural Yunnan province, China, whose residents use a variety of solid fuels for cooking and heating including bituminous and anthracite coal, and wood. Measurements were taken over two consecutive 24-h periods from 163 households in 30 villages. PM2.5 absorbance (PMabs ) was measured using an EEL 043 Smoke Stain Reflectometer. PMabs measurements were higher in wood burning households (16.3 × 10(-5) /m) than bituminous and anthracite coal households (12 and 5.1 × 10(-5) /m, respectively). Among bituminous coal users, measurements varied by a factor of two depending on the coal source. Portable stoves (which are lit outdoors and brought indoors for use) were associated with reduced PMabs levels, but no other impact of stove design was observed. Outdoor measurements were positively correlated with and approximately half the level of indoor measurements (r = 0.49, P < 0.01). Measurements of BC (as approximated by PMabs ) in this population are modulated by fuel type and source. This provides valuable insight into potential morbidity, mortality, and climate change contributions of domestic usage of solid fuels.
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Poluição do Ar/análise , Culinária/instrumentação , Exposição Ambiental/análise , Fumaça/análise , Fuligem/análise , China , Carvão Mineral , Culinária/métodos , Calefação/instrumentação , Calefação/métodos , Humanos , Material Particulado/análise , População Rural , MadeiraRESUMO
BACKGROUND: The aim of this work was to examine the risk of lymphohaematopoietic (LH) cancer according to benzene exposure among offshore workers. METHODS: Cancer registry data were used to identify 112 cancer cases diagnosed during 1999-2011 in a cohort of 24 917 Norwegian men reporting offshore work between 1965 and 1999. Analyses were conducted according to a stratified case-cohort design with a reference subcohort of 1661 workers. Cox regression was used to estimate hazard ratios with 95% confidence intervals, adjusted for other benzene exposure and smoking. RESULTS: Most workers were exposed to benzene for <15 years. The upper range values of average intensity and cumulative exposure were estimated to 0.040 p.p.m. and 0.948 p.p.m.-years, respectively. Risks were consistently elevated among exposed workers for all LH cancers combined and for most subgroups, although case numbers were small and yielded imprecise risk estimates. There was evidence of dose-related risk patterns according to cumulative exposure for acute myeloid leukaemia (AML), multiple myeloma (MM) (P trends 0.052 and 0.024, respectively), and suggestively so for chronic lymphocytic leukaemia (CLL) according to average intensity (P trend 0.094). CONCLUSIONS: Our results support an association between cumulative and intensity metrics of low-level benzene exposure and risk for AML, MM, and suggestively for CLL.
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Benzeno/efeitos adversos , Neoplasias Hematológicas/epidemiologia , Leucemia/epidemiologia , Linfoma/epidemiologia , Doenças Profissionais/epidemiologia , Exposição Ocupacional/efeitos adversos , Petróleo/efeitos adversos , Adolescente , Adulto , Idoso , Estudos de Casos e Controles , Estudos de Coortes , Seguimentos , Neoplasias Hematológicas/induzido quimicamente , Humanos , Leucemia/induzido quimicamente , Linfoma/induzido quimicamente , Masculino , Pessoa de Meia-Idade , Noruega/epidemiologia , Doenças Profissionais/induzido quimicamente , Prognóstico , Fatores de Risco , Adulto JovemAssuntos
Biomarcadores Tumorais/sangue , Antígeno Ki-1/sangue , Linfoma não Hodgkin/sangue , Receptores de IgE/sangue , Estudos de Casos e Controles , Estudos de Coortes , Ensaio de Imunoadsorção Enzimática , Seguimentos , Humanos , Linfoma não Hodgkin/diagnóstico , Linfoma não Hodgkin/etiologia , Masculino , Prognóstico , Fatores de RiscoRESUMO
BACKGROUND: Aberrant global DNA methylation is shown to increase cancer risk. LINE-1 has been proven a measure of global DNA methylation. The objectives of this study were to assess the association between LINE-1 methylation level and bladder cancer risk and to evaluate effect modification by environmental and genetic factors. METHODS: Bisulphite-treated leukocyte DNA from 952 cases and 892 hospital controls was used to measure LINE-1 methylation level at four CpG sites by pyrosequencing. Logistic regression model was fitted to estimate odds ratios (ORs) and 95% confidence intervals (95% CIs). Interactions between LINE-1 methylation levels and environmental and genetic factors were assessed. RESULTS: The risk of bladder cancer followed a nonlinear association with LINE-1 methylation. Compared with subjects in the middle tertile, the adjusted OR for subjects in the lower and the higher tertiles were 1.26 (95% CI 0.99-1.60, P=0.06) and 1.33 (95% CI 1.05-1.69, P=0.02), respectively. This association significantly increased among individuals homozygous for the major allele of five single-nucleotide polymorphisms located in the phosphatidylethanolamine N-methyltransferase gene (corrected P-interaction<0.05). CONCLUSIONS: The findings from this large-scale study suggest that both low and high levels of global DNA methylation are associated with the risk of bladder cancer.
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Metilação de DNA/genética , Elementos Nucleotídeos Longos e Dispersos/genética , Fosfatidiletanolamina N-Metiltransferase/genética , Neoplasias da Bexiga Urinária/genética , Idoso , Idoso de 80 Anos ou mais , Ilhas de CpG/genética , Feminino , Estudos de Associação Genética , Predisposição Genética para Doença , Sequenciamento de Nucleotídeos em Larga Escala , Humanos , Leucócitos/patologia , Masculino , Pessoa de Meia-Idade , Polimorfismo de Nucleotídeo Único , Fatores de Risco , Neoplasias da Bexiga Urinária/patologiaRESUMO
OBJECTIVES: We evaluated the association between occupational exposure to trichloroethylene (TCE) and risk of non-Hodgkin lymphoma (NHL) in a pooled analysis of four international case-control studies. METHODS: Overall, the pooled study population included 3788 NHL cases and 4279 controls. Risk of NHL and its major subtypes associated with TCE exposure was calculated with unconditional logistic regression and polytomous regression analysis, adjusting by age, gender and study. RESULTS: Risk of follicular lymphoma (FL), but not NHL overall or other subtypes, increased by probability (p=0.02) and intensity level (p=0.04), and with the combined analysis of four exposure metrics assumed as independent (p=0.004). After restricting the analysis to the most likely exposed study subjects, risk of NHL overall, FL and chronic lymphocytic leukaemia (CLL) were elevated and increased by duration of exposure (p=0.009, p=0.04 and p=0.01, respectively) and with the combined analysis of duration, frequency and intensity of exposure (p=0.004, p=0.015 and p=0.005, respectively). Although based on small numbers of exposed, risk of all the major NHL subtypes, namely diffuse large B-cell lymphoma, FL and CLL, showed increases in risk ranging 2-3.2-fold in the highest category of exposure intensity. No significant heterogeneity in risk was detected by major NHL subtypes or by study. CONCLUSIONS: Our pooled analysis apparently supports the hypothesis of an increase in risk of specific NHL subtypes associated with occupational exposure to TCE.
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Leucemia Linfocítica Crônica de Células B/induzido quimicamente , Linfoma Folicular/induzido quimicamente , Linfoma Difuso de Grandes Células B/induzido quimicamente , Doenças Profissionais/induzido quimicamente , Exposição Ocupacional/efeitos adversos , Tricloroetileno/toxicidade , Adulto , Idoso , Estudos de Casos e Controles , Feminino , Humanos , Linfoma não Hodgkin/induzido quimicamente , Masculino , Pessoa de Meia-Idade , Análise de Regressão , Fatores de RiscoRESUMO
BACKGROUND: No prospective study has investigated the relationship between type 2 diabetes mellitus (T2DM) and the risk of primary liver cancer (PLC) in mainland China, and little is known about the effect of diabetes duration on PLC risk. DESIGN: Data from two population-based cohorts (the Shanghai Men's Health Study, SMHS, 2002-2006 and the Shanghai Women's Health Study, SWHS, 1996-2000) were thus used to assess the associations among T2DM, diabetes duration and PLC risk in Chinese population. RESULTS: During follow-up through 2009, 344 incident PLC cases were identified among 60 183 men and 73 105 women. T2DM is significantly associated with the increased risk of PLC in both men [hazard ratio (HR) = 1.63, 95% confidence interval (CI) 1.06-2.51] and women (HR = 1.64, 95% CI 1.03-2.61). The highest risk of incident liver cancer was observed in the first 5 years after diabetes diagnosis, and decreased substantially with the prolonged diabetes duration (P(trend) < 0.001). No synergistic interaction in the development of PLC was found between diabetes and other known risk factors. CONCLUSIONS: T2DM is associated with the increased risk of subsequent liver cancer within 5 years after diagnosis in Chinese population, suggesting that hyperinsulinaemia rather than hyperglycaemia is more likely to be a primary mediator for this association.
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Povo Asiático/etnologia , Diabetes Mellitus Tipo 2/diagnóstico , Diabetes Mellitus Tipo 2/etnologia , Neoplasias Hepáticas/diagnóstico , Neoplasias Hepáticas/etnologia , Vigilância da População , Adulto , Idoso , Povo Asiático/genética , China/etnologia , Estudos de Coortes , Diabetes Mellitus Tipo 2/genética , Feminino , Seguimentos , Humanos , Neoplasias Hepáticas/genética , Masculino , Pessoa de Meia-Idade , Vigilância da População/métodos , Estudos Prospectivos , Fatores de Risco , Inquéritos e QuestionáriosRESUMO
Benzene exposure causes acute myeloid leukemia and hematotoxicity, shown as suppression of mature blood and myeloid progenitor cell numbers. As the leukemia-related aneuploidies monosomy 7 and trisomy 8 previously had been detected in the mature peripheral blood cells of exposed workers, we hypothesized that benzene could cause leukemia through the induction of these aneuploidies in hematopoietic stem and progenitor cells. We measured loss and gain of chromosomes 7 and 8 by fluorescence in situ hybridization in interphase colony-forming unit-granulocyte-macrophage (CFU-GM) cells cultured from otherwise healthy benzene-exposed (n=28) and unexposed (n=14) workers. CFU-GM monosomy 7 and 8 levels (but not trisomy) were significantly increased in subjects exposed to benzene overall, compared with levels in the control subjects (P=0.0055 and P=0.0034, respectively). Levels of monosomy 7 and 8 were significantly increased in subjects exposed to <10 p.p.m. (20%, P=0.0419 and 28%, P=0.0056, respectively) and ≥ 10 p.p.m. (48%, P=0.0045 and 32%, 0.0354) benzene, compared with controls, and significant exposure-response trends were detected (P(trend)=0.0033 and 0.0057). These data show that monosomies 7 and 8 are produced in a dose-dependent manner in the blood progenitor cells of workers exposed to benzene, and may be mechanistically relevant biomarkers of early effect for benzene and other leukemogens.
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Benzeno/efeitos adversos , Deleção Cromossômica , Cromossomos Humanos Par 7/genética , Cromossomos Humanos Par 8/genética , Leucemia Mieloide Aguda/induzido quimicamente , Monossomia , Exposição Ocupacional/efeitos adversos , Adulto , Aneuploidia , Estudos de Casos e Controles , Ensaio de Unidades Formadoras de Colônias , Estudos Transversais , Feminino , Seguimentos , Humanos , Hibridização in Situ Fluorescente , Leucemia Mieloide Aguda/genética , Leucemia Mieloide Aguda/patologia , Masculino , PrognósticoRESUMO
BACKGROUND: Despite many studies on diet and bladder cancer, there are areas that remain unexplored including meat mutagens, specific vegetable groups, and vitamins from diet. METHODS: We conducted a population-based case-control study of bladder cancer in Maine, New Hampshire, and Vermont. A total of 1171 cases were ascertained through hospital pathology records and cancer registries from 2001 to 2004. Overall, 1418 controls were identified from the Department of Motor Vehicles (<65 years) and Center for Medicaid and Medicare Services (65-79 years) and were frequency-matched to cases by state, sex, and age (within 5 years). Diet was assessed with a self-administered Diet History Questionnaire. Unconditional logistic regression was used to estimate odds ratios (OR) and 95% confidence intervals (CI). RESULTS: Processed meat intake was positively associated with bladder cancer (highest vs lowest quartile OR: 1.28; 95% CI: 1.00-1.65; P(trend)=0.035), with a stronger association for processed red meat (OR: 1.41; 95% CI: 1.08-1.84; P(trend)=0.024). There were no associations between intake of fruits or vegetables and bladder cancer. We did, however, observe an inverse association with vitamin B12 intake (OR: 0.77; 95% CI: 0.61-0.99; P=0.019). CONCLUSION: Vitamin B12 from diet may be protective against bladder cancer, whereas consuming processed meat may increase risk.
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Dieta , Frutas , Carne/efeitos adversos , Micronutrientes , Neoplasias da Bexiga Urinária/epidemiologia , Verduras , Adulto , Idoso , Animais , Estudos de Casos e Controles , Dieta/efeitos adversos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , New England/epidemiologia , Fatores de Risco , Complexo Vitamínico BRESUMO
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.
Assuntos
Elementos Alu , Leucócitos/metabolismo , Elementos Nucleotídeos Longos e Dispersos , Neoplasias Gástricas/epidemiologia , Adulto , Idoso , Elementos Alu/genética , Estudos de Casos e Controles , China/epidemiologia , Metilação de DNA , DNA de Neoplasias/análise , DNA de Neoplasias/metabolismo , Feminino , Promoção da Saúde , Humanos , Elementos Nucleotídeos Longos e Dispersos/genética , Pessoa de Meia-Idade , Estudos Prospectivos , Sistema de Registros , Fatores de Risco , Neoplasias Gástricas/sangue , Saúde da MulherRESUMO
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.
Assuntos
Carcinoma de Células Renais/sangue , Carcinoma de Células Renais/genética , Neoplasias Renais/sangue , Neoplasias Renais/genética , Telômero/genética , Adolescente , Adulto , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Estudos de Casos e Controles , Criança , Pré-Escolar , Feminino , Humanos , Hipertensão/genética , Lactente , Recém-Nascido , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Fatores de Risco , Estados Unidos , Adulto JovemRESUMO
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.
Assuntos
Adenocarcinoma/etiologia , Carcinoma de Células Renais/etiologia , Culinária , Neoplasias Renais/etiologia , Carne/efeitos adversos , Mutagênicos/efeitos adversos , Adenocarcinoma/epidemiologia , Adulto , Idoso , Carcinoma de Células Renais/epidemiologia , Estudos de Casos e Controles , Chicago/epidemiologia , Feminino , Seguimentos , Humanos , Neoplasias Renais/epidemiologia , Pessoa de Meia-Idade , Prognóstico , Fatores de Risco , Taxa de Sobrevida , Adulto JovemRESUMO
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.
Assuntos
Atividade Motora , Adulto , Idoso , Povo Asiático , Neoplasias da Mama , Metabolismo Energético , Feminino , Humanos , Incidência , Pessoa de Meia-Idade , Ocupações , Estudos Prospectivos , Comportamento Sedentário , CaminhadaRESUMO
BACKGROUND: XuanWei County, Yunnan province, has the highest lung cancer mortality rates among men and women in China. The high mortality has been linked to the use of smoky (bituminous) coal for heating and cooking. Research to date has suggested that exposure to polycyclic aromatic hydrocarbons (PAHs) is one of the main contributors to the observed risk. More recently exposure to crystalline silica has been suggested as another contributing factor. METHODS: We used data of indoor benzo[a]pyrene (BaP) and silica level and lung cancer mortality at the communal level from previous reports to discuss etiological hypotheses on the lung cancer epidemics in XuanWei County. RESULTS: We estimated that PAH exposure as measured by benzo[a]pyrene (BaP) can explain a significant part of the excess risk but not fully (Odd Ratio (OR) 3 as compared to an observed OR = 8 for smoky coal users versus smokeless coal users). This leaves open the possibility of other contributing exposures. Exposure to crystalline silica however would likely only result in an increased risk (OR) of less than 1.5 and as such silica seems not to be the main exposure of interest. However, this does not exclude that risks are present because of the specific physic-chemical characteristics of the silica in smoky coal or that there is an interaction between silica and PAH exposures. CONCLUSION: More detailed exposure assessment of indoor air pollution due to the use of smoky coal and subsequent linkage on an individual level to ongoing epidemiological studies should provide more insight in the etiology of lung cancer in this region.