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1.
Int J Cancer ; 149(11): 1887-1897, 2021 12 01.
Artigo em Inglês | MEDLINE | ID: mdl-34278567

RESUMO

Particulate matter air pollution and diesel engine exhaust have been classified as carcinogenic for lung cancer, yet few studies have explored associations with liver cancer. We used six European adult cohorts which were recruited between 1985 and 2005, pooled within the "Effects of low-level air pollution: A study in Europe" (ELAPSE) project, and followed for the incidence of liver cancer until 2011 to 2015. The annual average exposure to nitrogen dioxide (NO2 ), particulate matter with diameter <2.5 µm (PM2.5 ), black carbon (BC), warm-season ozone (O3 ), and eight elemental components of PM2.5 (copper, iron, zinc, sulfur, nickel, vanadium, silicon, and potassium) were estimated by European-wide hybrid land-use regression models at participants' residential addresses. We analyzed the association between air pollution and liver cancer incidence by Cox proportional hazards models adjusting for potential confounders. Of 330 064 cancer-free adults at baseline, 512 developed liver cancer during a mean follow-up of 18.1 years. We observed positive linear associations between NO2 (hazard ratio, 95% confidence interval: 1.17, 1.02-1.35 per 10 µg/m3 ), PM2.5 (1.12, 0.92-1.36 per 5 µg/m3 ), and BC (1.15, 1.00-1.33 per 0.5 10-5 /m) and liver cancer incidence. Associations with NO2 and BC persisted in two-pollutant models with PM2.5 . Most components of PM2.5 were associated with the risk of liver cancer, with the strongest associations for sulfur and vanadium, which were robust to adjustment for PM2.5 or NO2 . Our study suggests that ambient air pollution may increase the risk of liver cancer, even at concentrations below current EU standards.


Assuntos
Poluição do Ar/efeitos adversos , Exposição Ambiental/efeitos adversos , Neoplasias Hepáticas/etiologia , Adulto , Poluentes Atmosféricos/toxicidade , Poluição do Ar/estatística & dados numéricos , Exposição Ambiental/estatística & dados numéricos , Europa (Continente)/epidemiologia , Feminino , Humanos , Incidência , Neoplasias Hepáticas/epidemiologia , Masculino , Pessoa de Meia-Idade , Tamanho da Partícula , Material Particulado/toxicidade , Modelos de Riscos Proporcionais
2.
Int J Cancer ; 149(1): 66-74, 2021 07 01.
Artigo em Inglês | MEDLINE | ID: mdl-33634882

RESUMO

To explore the largely unknown etiology of small intestine cancer, we examined metabolic factors and risk of small intestine cancer overall and by subtypes. Among 404 220 women and 403 265 men in six European cohorts, we applied Cox regression with adjustment for smoking and body mass index (BMI), to calculate sex-specific hazard ratios (HRs) of small intestine cancer by levels of BMI, mean arterial pressure (MAP) and plasma total cholesterol, triglycerides and glucose. We also calculated HRs for these factors combined (metabolic score; MetS) and used Wald test statistics to investigate pairwise interactions between metabolic factors on risk. We also performed analyses separately per subtype (neuroendocrine tumors [NETs] and adenocarcinomas). During a median follow-up of 16.9 years, 144 women and 195 men were diagnosed with small intestine cancer, including 184 NETs and 99 adenocarcinomas. Among men, no main associations or interactions between metabolic factors were observed in relation to the risk of small intestine cancer. Among women, triglycerides were positively and linearly associated with risk (HR per standard deviation [SD]: 1.23, 95% confidence interval [CI]: 1.04-1.46), and a positive association was also observed for the MetS (HR per SD: 1.25, 95% CI: 1.02-1.52). Positive interactions were observed among women between triglycerides and cholesterol (P = .0005), and between MAP and glucose (P = .009), on risk. Glucose was positively associated with adenocarcinomas among women. This large, prospective study suggests that elevated triglycerides, and metabolic factors in interaction, confer an increased risk of small intestine cancer among women, but not among men.


Assuntos
Adenocarcinoma/patologia , Biomarcadores/análise , Neoplasias Intestinais/patologia , Intestino Delgado/patologia , Síndrome Metabólica/complicações , Adenocarcinoma/epidemiologia , Adenocarcinoma/etiologia , Adulto , Pressão Sanguínea , Índice de Massa Corporal , Europa (Continente)/epidemiologia , Feminino , Seguimentos , Humanos , Neoplasias Intestinais/epidemiologia , Neoplasias Intestinais/etiologia , Masculino , Pessoa de Meia-Idade , Prognóstico , Estudos Prospectivos , Fatores de Risco
3.
Environ Int ; 146: 106249, 2021 01.
Artigo em Inglês | MEDLINE | ID: mdl-33197787

RESUMO

BACKGROUND/AIM: Ambient air pollution has been associated with lung cancer, but the shape of the exposure-response function - especially at low exposure levels - is not well described. The aim of this study was to address the relationship between long-term low-level air pollution exposure and lung cancer incidence. METHODS: The "Effects of Low-level Air Pollution: a Study in Europe" (ELAPSE) collaboration pools seven cohorts from across Europe. We developed hybrid models combining air pollution monitoring, land use data, satellite observations, and dispersion model estimates for nitrogen dioxide (NO2), fine particulate matter (PM2.5), black carbon (BC), and ozone (O3) to assign exposure to cohort participants' residential addresses in 100 m by 100 m grids. We applied stratified Cox proportional hazards models, adjusting for potential confounders (age, sex, calendar year, marital status, smoking, body mass index, employment status, and neighborhood-level socio-economic status). We fitted linear models, linear models in subsets, Shape-Constrained Health Impact Functions (SCHIF), and natural cubic spline models to assess the shape of the association between air pollution and lung cancer at concentrations below existing standards and guidelines. RESULTS: The analyses included 307,550 cohort participants. During a mean follow-up of 18.1 years, 3956 incident lung cancer cases occurred. Median (Q1, Q3) annual (2010) exposure levels of NO2, PM2.5, BC and O3 (warm season) were 24.2 µg/m3 (19.5, 29.7), 15.4 µg/m3 (12.8, 17.3), 1.6 10-5m-1 (1.3, 1.8), and 86.6 µg/m3 (78.5, 92.9), respectively. We observed a higher risk for lung cancer with higher exposure to PM2.5 (HR: 1.13, 95% CI: 1.05, 1.23 per 5 µg/m3). This association was robust to adjustment for other pollutants. The SCHIF, spline and subset analyses suggested a linear or supra-linear association with no evidence of a threshold. In subset analyses, risk estimates were clearly elevated for the subset of subjects with exposure below the EU limit value of 25 µg/m3. We did not observe associations between NO2, BC or O3 and lung cancer incidence. CONCLUSIONS: Long-term ambient PM2.5 exposure is associated with lung cancer incidence even at concentrations below current EU limit values and possibly WHO Air Quality Guidelines.


Assuntos
Poluentes Atmosféricos , Poluição do Ar , Neoplasias Pulmonares , Poluentes Atmosféricos/análise , Poluição do Ar/efeitos adversos , Poluição do Ar/análise , Exposição Ambiental/análise , Europa (Continente)/epidemiologia , Humanos , Neoplasias Pulmonares/induzido quimicamente , Neoplasias Pulmonares/epidemiologia , Material Particulado/análise
4.
Environ Res ; 193: 110568, 2021 02.
Artigo em Inglês | MEDLINE | ID: mdl-33278469

RESUMO

BACKGROUND: An association between long-term exposure to fine particulate matter (PM2.5) and lung cancer has been established in previous studies. PM2.5 is a complex mixture of chemical components from various sources and little is known about whether certain components contribute specifically to the associated lung cancer risk. The present study builds on recent findings from the "Effects of Low-level Air Pollution: A Study in Europe" (ELAPSE) collaboration and addresses the potential association between specific elemental components of PM2.5 and lung cancer incidence. METHODS: We pooled seven cohorts from across Europe and assigned exposure estimates for eight components of PM2.5 representing non-tail pipe emissions (copper (Cu), iron (Fe), and zinc (Zn)), long-range transport (sulfur (S)), oil burning/industry emissions (nickel (Ni), vanadium (V)), crustal material (silicon (Si)), and biomass burning (potassium (K)) to cohort participants' baseline residential address based on 100 m by 100 m grids from newly developed hybrid models combining air pollution monitoring, land use data, satellite observations, and dispersion model estimates. We applied stratified Cox proportional hazards models, adjusting for potential confounders (age, sex, calendar year, marital status, smoking, body mass index, employment status, and neighborhood-level socio-economic status). RESULTS: The pooled study population comprised 306,550 individuals with 3916 incident lung cancer events during 5,541,672 person-years of follow-up. We observed a positive association between exposure to all eight components and lung cancer incidence, with adjusted HRs of 1.10 (95% CI 1.05, 1.16) per 50 ng/m3 PM2.5 K, 1.09 (95% CI 1.02, 1.15) per 1 ng/m3 PM2.5 Ni, 1.22 (95% CI 1.11, 1.35) per 200 ng/m3 PM2.5 S, and 1.07 (95% CI 1.02, 1.12) per 200 ng/m3 PM2.5 V. Effect estimates were largely unaffected by adjustment for nitrogen dioxide (NO2). After adjustment for PM2.5 mass, effect estimates of K, Ni, S, and V were slightly attenuated, whereas effect estimates of Cu, Si, Fe, and Zn became null or negative. CONCLUSIONS: Our results point towards an increased risk of lung cancer in connection with sources of combustion particles from oil and biomass burning and secondary inorganic aerosols rather than non-exhaust traffic emissions. Specific limit values or guidelines targeting these specific PM2.5 components may prove helpful in future lung cancer prevention strategies.


Assuntos
Poluentes Atmosféricos , Poluição do Ar , Neoplasias Pulmonares , Poluentes Atmosféricos/análise , Poluição do Ar/efeitos adversos , Poluição do Ar/análise , Exposição Ambiental/análise , Europa (Continente)/epidemiologia , Humanos , Incidência , Neoplasias Pulmonares/induzido quimicamente , Neoplasias Pulmonares/epidemiologia , Material Particulado/análise
5.
Wien Klin Wochenschr ; 132(15-16): 415-422, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32533444

RESUMO

BACKGROUND: Several clinical trials in chronic phase (CP) chronic myeloid leukemia (CML) showed that early response to tyrosine kinase inhibitor (TKI) treatment results in an improved long-term survival and progression-free survival. This study assessed whether patients achieving early treatment response (ETR; partial cytogenetic response or BCR-ABL1 mRNA ≤10% at 3 months) in daily practice also have a long-term survival benefit. METHODS: The Retrospective Evaluation of Early response in CML for long-term Treatment outcome (R-EFECT), a multicenter, retrospective chart review, documented patients with newly diagnosed CML-CP starting first-line TKI therapy in routine clinical practice. The primary aim was to assess the 5­year overall survival rate. RESULTS: Of the 211 patients from 12 centers across Austria (January 2004-May 2010), 176 (median age, 56 years) were included in the analysis. All patients received first-line therapy with imatinib. Overall, 136 patients (77.3%) achieved ETR (ETR+ group), whereas 40 (22.7%) did not reach ETR (ETR- group). The ETR+ group had higher 5­year overall survival (92.5% vs. 77.5%, P = 0.018) and progression-free survival (95.6% vs. 87.5%, P = 0.06) rates compared with the ETR- group. As expected, more patients in the ETR- group were switched to another TKI. At the last contact, 120 patients were still on imatinib and 44 had switched to another TKI (25 to nilotinib, 15 to dasatinib, and 4 to bosutinib). CONCLUSION: The data are in line with randomized trials demonstrating that ETR is associated with improved survival and thus confirmed these results in patients treated in daily clinical routine.


Assuntos
Antineoplásicos , Leucemia Mielogênica Crônica BCR-ABL Positiva , Leucemia Mieloide de Fase Crônica , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Antineoplásicos/uso terapêutico , Áustria , Dasatinibe/uso terapêutico , Feminino , Humanos , Leucemia Mielogênica Crônica BCR-ABL Positiva/diagnóstico , Leucemia Mielogênica Crônica BCR-ABL Positiva/tratamento farmacológico , Leucemia Mielogênica Crônica BCR-ABL Positiva/genética , Leucemia Mieloide de Fase Crônica/tratamento farmacológico , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Resultado do Tratamento , Adulto Jovem
6.
Breast ; 50: 64-70, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-32062536

RESUMO

BACKGROUND: STEPAUT, an Austrian non-interventional study, evaluated the safety and efficacy of everolimus plus exemestane in patients with hormone receptor-positive (HR+), human epidermal growth factor receptor 2-negative (HER2-) advanced breast cancer (ABC) recurring/progressing on/after nonsteroidal aromatase inhibitors (NSAIs) in routine clinical practice. METHODS: Postmenopausal women with HR+, HER2- ABC progressing on/after NSAIs receiving everolimus plus exemestane in accordance with routine practice and the current version of Summary of Product Characteristics were eligible. Planned individual observation period corresponded to the duration of treatment until formal study end. RESULTS: Overall, 236 patients (median age: 65 years) were enrolled at 17 sites across Austria. The median progression-free survival (mPFS) in the overall population was 9.5 months (95% confidence interval [CI]: 8.6-10.7 months). The mPFS (95% CI) in patients who received everolimus 10 and 5 mg was 9.9 months (7.3-11.5 months) and 8 months (4.7-10.7 months), respectively. The median time to progression was numerically longer in patients who had a therapy break (11.9 months, 95% CI: 10.0-14.6 months) versus those who did not have any therapy break (10.7 months, 95% CI: 8.9-12.6 months). Patients experienced grade 1 (53.7%), grade 2 (35.9%), grade 3 (9.9%), grade 4 (0.2%) adverse events (AEs). The most common AEs of any grade were stomatitis, mucositis (53.8%), rash, exanthema (29.7%), loss of appetite, nausea (28.4%). CONCLUSIONS: Real-world safety and efficacy data from STEPAUT were consistent with results from BOLERO-2, supporting everolimus plus exemestane as a suitable treatment option for HR+, HER2- ABC recurring/progressing on/after NSAIs.


Assuntos
Androstadienos/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Inibidores da Aromatase/uso terapêutico , Neoplasias da Mama/tratamento farmacológico , Everolimo/uso terapêutico , Padrões de Prática Médica , Idoso , Áustria/epidemiologia , Feminino , Humanos , Pós-Menopausa , Intervalo Livre de Progressão , Receptor ErbB-2/metabolismo , Receptores de Estrogênio/metabolismo , Receptores de Progesterona/metabolismo
7.
Int J Cancer ; 146(1): 58-67, 2020 01 01.
Artigo em Inglês | MEDLINE | ID: mdl-30815851

RESUMO

Apart from the consistently observed differential association between obesity and breast cancer risk by menopausal status, the associations between obesity and other metabolic imbalances with risks of cancers have not been systematically investigated across the age-course. We created two random 50-50% cohorts from six European cohorts comprising 813,927 individuals. In the "discovery cohort", we used Cox regression with attained age as time-scale and tested interactions between body mass index (BMI), blood pressure, plasma glucose, triglycerides and cholesterol, and attained age in relation to cancer risk. Results with a p-value below 0.05 were additionally tested in the "replication cohort" where a replicated result was considered evidence of a linear interaction with attained age. These findings were investigated by flexible parametric survival models for any age-plateaus in their shape of associations with cancer risk across age. Consistent with other studies, BMI was negatively related to breast cancer risk (n cases = 11,723) among younger (premenopausal) women. However, the association remained negative for several years after menopause and, although gradually weakening over age, the association became positive only at 62 years of age. This linear and positive age-interaction was also found for triglycerides and breast cancer, and for BMI and triglycerides in relation to liver cancer among men (n cases = 444). These findings are unlikely to be due to chance owing to the replication. The linear age-interactions in breast cancer may suggest an influence by other age-related factors than menopause; however, further investigation of age-related effect modifiers in both breast and liver cancer is needed.


Assuntos
Fatores Etários , Índice de Massa Corporal , Neoplasias da Mama/epidemiologia , Neoplasias Hepáticas/epidemiologia , Triglicerídeos/sangue , Adulto , Glicemia/metabolismo , Pressão Sanguínea , Neoplasias da Mama/sangue , Colesterol/sangue , Estudos de Coortes , Feminino , Humanos , Neoplasias Hepáticas/sangue , Masculino , Reprodutibilidade dos Testes , Fatores de Risco
8.
Int J Epidemiol ; 49(1): 193-204, 2020 02 01.
Artigo em Inglês | MEDLINE | ID: mdl-30945727

RESUMO

BACKGROUND: The role of insulin resistance as a mediator in the association of body mass index (BMI) with site-specific cancer risk has, to our knowledge, never been systematically quantified. METHODS: Altogether 510 471 individuals from six European cohorts, with a mean age of 43.1 years, were included. We used the triglyceride glucose product (TyG index) as a surrogate measure for insulin resistance. We fitted Cox models, adjusted for relevant confounders, to investigate associations of TyG index with 10 common obesity-related cancers, and quantified the proportion of the effect of BMI mediated through TyG index on the log-transformed hazard ratio (HR) scale. RESULTS: During a median follow-up of 17.2 years, 16 052 individuals developed obesity-related cancers. TyG index was associated with the risk of cancers of the kidney HR per one standard deviation increase 1.13, 95% confidence interval: 1.07 to 1.20], liver (1.13, 1.04 to 1.23), pancreas (1.12, 1.06 to 1.19), colon (1.07, 1.03 to 1.10) and rectum (1.09, 1.04 to 1.14). Substantial proportions of the effect of BMI were mediated by TyG index for cancers of the pancreas (42%), rectum (34%) and colon (20%); smaller proportions for kidney (15%) and liver (11%). Little or no mediation was observed for breast (postmenopausal), endometrial and ovarian cancer. Results were similar for males and females, except for pancreatic cancer where the proportions mediated were 20% and 91%, respectively. CONCLUSIONS: The TyG index was associated with increased risk of cancers of the digestive system and substantially mediated the effect of BMI, suggesting that insulin resistance plays a promoting role in the pathogenesis of gastrointestinal cancers.


Assuntos
Glicemia/metabolismo , Diabetes Mellitus Tipo 2/epidemiologia , Neoplasias/epidemiologia , Obesidade/sangue , Obesidade/epidemiologia , Adulto , Biomarcadores/sangue , Índice de Massa Corporal , Estudos de Coortes , Diabetes Mellitus Tipo 2/sangue , Feminino , Glucose , Humanos , Resistência à Insulina , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Neoplasias/sangue , Fatores de Risco , Triglicerídeos/sangue
9.
Int J Epidemiol ; 48(6): 1872-1885, 2019 12 01.
Artigo em Inglês | MEDLINE | ID: mdl-31566221

RESUMO

BACKGROUND: Obesity is an established risk factor for several cancers. Adult weight gain has been associated with increased cancer risk, but studies on timing and duration of adult weight gain are relatively scarce. We examined the impact of BMI (body mass index) and weight changes over time, as well as the timing and duration of excess weight, on obesity- and non-obesity-related cancers. METHODS: We pooled health data from six European cohorts and included 221 274 individuals with two or more height and weight measurements during 1972-2014. Several BMI and weight measures were constructed. Cancer cases were identified through linkage with national cancer registries. Hazard ratios (HRs) of cancer with 95% confidence intervals (CIs) were derived from time-dependent Cox-regression models. RESULTS: During follow-up, 27 881 cancer cases were diagnosed; 9761 were obesity-related. The HR of all obesity-related cancers increased with increasing BMI at first and last measurement, maximum BMI and longer duration of overweight (men only) and obesity. Participants who were overweight before age 40 years had an HR of obesity-related cancers of 1.16 (95% CI 1.02, 1.32) and 1.15 (95% CI 1.04, 1.27) in men and women, respectively, compared with those who were not overweight. The risk increase was particularly high for endometrial (70%), male renal-cell (58%) and male colon cancer (29%). No positive associations were seen for cancers not regarded as obesity-related. CONCLUSIONS: Adult weight gain was associated with increased risk of several major cancers. The degree, timing and duration of overweight and obesity also seemed to be important. Preventing weight gain may reduce the cancer risk.


Assuntos
Índice de Massa Corporal , Neoplasias/epidemiologia , Obesidade/epidemiologia , Sobrepeso/epidemiologia , Ganho de Peso , Adulto , Estudos de Coortes , Neoplasias do Colo/epidemiologia , Europa (Continente)/epidemiologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Modelos de Riscos Proporcionais , Sistema de Registros , Fatores de Risco , Distribuição por Sexo , Fatores de Tempo
10.
Cancer Cell ; 35(2): 256-266.e5, 2019 02 11.
Artigo em Inglês | MEDLINE | ID: mdl-30753826

RESUMO

Biallelic germline mutations affecting NTHL1 predispose carriers to adenomatous polyposis and colorectal cancer, but the complete phenotype is unknown. We describe 29 individuals carrying biallelic germline NTHL1 mutations from 17 families, of which 26 developed one (n = 10) or multiple (n = 16) malignancies in 14 different tissues. An unexpected high breast cancer incidence was observed in female carriers (60%). Mutational signature analysis of 14 tumors from 7 organs revealed that NTHL1 deficiency underlies the main mutational process in all but one of the tumors (93%). These results reveal NTHL1 as a multi-tumor predisposition gene with a high lifetime risk for extracolonic cancers and a typical mutational signature observed across tumor types, which can assist in the recognition of this syndrome.


Assuntos
Biomarcadores Tumorais/genética , Análise Mutacional de DNA , Desoxirribonuclease (Dímero de Pirimidina)/genética , Perfilação da Expressão Gênica , Mutação em Linhagem Germinativa , Síndromes Neoplásicas Hereditárias/genética , Transcriptoma , Adulto , Idoso , Biomarcadores Tumorais/deficiência , Reparo do DNA/genética , Desoxirribonuclease (Dímero de Pirimidina)/deficiência , Europa (Continente) , Feminino , Regulação Neoplásica da Expressão Gênica , Predisposição Genética para Doença , Hereditariedade , Humanos , Masculino , Pessoa de Meia-Idade , Síndromes Neoplásicas Hereditárias/enzimologia , Síndromes Neoplásicas Hereditárias/patologia , Linhagem , Fenótipo , Medição de Risco , Fatores de Risco , Adulto Jovem
11.
Environ Int ; 120: 163-171, 2018 11.
Artigo em Inglês | MEDLINE | ID: mdl-30096610

RESUMO

INTRODUCTION: Previous analysis from the large European multicentre ESCAPE study showed an association of ambient particulate matter <2.5 µm (PM2.5) air pollution exposure at residence with the incidence of gastric cancer. It is unclear which components of PM are most relevant for gastric and also upper aerodigestive tract (UADT) cancer and some of them may not be strongly correlated with PM mass. We evaluated the association between long-term exposure to elemental components of PM2.5 and PM10 and gastric and UADT cancer incidence in European adults. METHODS: Baseline addresses of individuals were geocoded and exposure was assessed by land-use regression models for copper (Cu), iron (Fe) and zinc (Zn) representing non-tailpipe traffic emissions; sulphur (S) indicating long-range transport; nickel (Ni) and vanadium (V) for mixed oil-burning and industry; silicon (Si) for crustal material and potassium (K) for biomass burning. Cox regression models with adjustment for potential confounders were used for cohort-specific analyses. Combined estimates were determined with random effects meta-analyses. RESULTS: Ten cohorts in six countries contributed data on 227,044 individuals with an average follow-up of 14.9 years with 633 incident cases of gastric cancer and 763 of UADT cancer. The combined hazard ratio (HR) for an increase of 200 ng/m3 of PM2.5_S was 1.92 (95%-confidence interval (95%-CI) 1.13;3.27) for gastric cancer, with no indication of heterogeneity between cohorts (I2 = 0%), and 1.63 (95%-CI 0.88;3.01) for PM2.5_Zn (I2 = 70%). For the other elements in PM2.5 and all elements in PM10 including PM10_S, non-significant HRs between 0.78 and 1.21 with mostly wide CIs were seen. No association was found between any of the elements and UADT cancer. The HR for PM2.5_S and gastric cancer was robust to adjustment for additional factors, including diet, and restriction to study participants with stable addresses over follow-up resulted in slightly higher effect estimates with a decrease in precision. In a two-pollutant model, the effect estimate for total PM2.5 decreased whereas that for PM2.5_S was robust. CONCLUSION: This large multicentre cohort study shows a robust association between gastric cancer and long-term exposure to PM2.5_S but not PM10_S, suggesting that S in PM2.5 or correlated air pollutants may contribute to the risk of gastric cancer.


Assuntos
Poluição do Ar , Exposição Ambiental , Material Particulado/análise , Neoplasias Gástricas/epidemiologia , Poluição do Ar/análise , Poluição do Ar/estatística & dados numéricos , Exposição Ambiental/análise , Exposição Ambiental/estatística & dados numéricos , Europa (Continente)/epidemiologia , Seguimentos , Humanos , Metais Pesados/análise , Modelos de Riscos Proporcionais
13.
Ann Hematol ; 97(10): 1825-1839, 2018 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-29862437

RESUMO

Despite recent advances, chemoimmunotherapy remains a standard for fit previously untreated chronic lymphocytic leukaemia patients. Lenalidomide had activity in early monotherapy trials, but tumour lysis and flare proved major obstacles in its development. We combined lenalidomide in increasing doses with six cycles of fludarabine and rituximab (FR), followed by lenalidomide/rituximab maintenance. In 45 chemo-naive patients, included in this trial, individual tolerability of the combination was highly divergent and no systematic toxicity determining a maximum tolerated dose was found. Grade 3/4 neutropenia (71%) was high, but only 7% experienced grade 3 infections. No tumour lysis or flare > grade 2 was observed, but skin toxicity proved dose-limiting in nine patients (20%). Overall and complete response rates after induction were 89 and 44% by intention-to-treat, respectively. At a median follow-up of 78.7 months, median progression-free survival (PFS) was 60.3 months. Minimal residual disease and immunoglobulin variable region heavy chain mutation state predicted PFS and TP53 mutation most strongly predicted OS. Baseline clinical factors did not predict tolerance to the immunomodulatory drug lenalidomide, but pretreatment immunophenotypes of T cells showed exhausted memory CD4 cells to predict early dose-limiting non-haematologic events. Overall, combining lenalidomide with FR was feasible and effective, but individual changes in the immune system seemed associated with limiting side effects. clinicaltrials.gov (NCT00738829) and EU Clinical Trials Register ( www.clinicaltrialsregister.eu , 2008-001430-27).


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Leucemia Linfocítica Crônica de Células B/tratamento farmacológico , Adulto , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Linfócitos T CD4-Positivos/efeitos dos fármacos , Linfócitos T CD4-Positivos/imunologia , Quimioterapia de Consolidação , Intervalo Livre de Doença , Relação Dose-Resposta a Droga , Esquema de Medicação , Erupção por Droga/etiologia , Feminino , Doenças Hematológicas/induzido quimicamente , Humanos , Imunidade Celular/efeitos dos fármacos , Memória Imunológica/efeitos dos fármacos , Imunoterapia , Estimativa de Kaplan-Meier , Lenalidomida , Leucemia Linfocítica Crônica de Células B/genética , Contagem de Linfócitos , Quimioterapia de Manutenção , Masculino , Dose Máxima Tolerável , Pessoa de Meia-Idade , Indução de Remissão , Rituximab/administração & dosagem , Rituximab/efeitos adversos , Subpopulações de Linfócitos T/efeitos dos fármacos , Talidomida/administração & dosagem , Talidomida/efeitos adversos , Talidomida/análogos & derivados , Talidomida/farmacologia , Resultado do Tratamento , Vidarabina/administração & dosagem , Vidarabina/efeitos adversos , Vidarabina/análogos & derivados
16.
Int J Cancer ; 143(12): 3071-3082, 2018 12 15.
Artigo em Inglês | MEDLINE | ID: mdl-29756343

RESUMO

Previous studies on metabolic factors and bladder cancer (BC) risk have shown inconsistent results and have commonly not investigated associations separately by sex, smoking, and tumor invasiveness. Among 811,633 participants in six European cohorts, we investigated sex-specific associations between body mass index (BMI), mid-blood pressure (BP, [systolic + diastolic]/2), plasma glucose, triglycerides, total cholesterol and risk of BC overall, non-muscle invasive BC (NMIBC) and muscle invasive BC (MIBC). Among men, we additionally assessed additive interactions between metabolic factors and smoking on BC risk. During follow-up, 2,983 men and 754 women were diagnosed with BC. Among men, triglycerides and BP were positively associated with BC risk overall (hazard ratio [HR] per standard deviation [SD]: 1.17 [95% confidence interval (CI) 1.06-1.27] and 1.09 [1.02-1.17], respectively), and among women, BMI was inversely associated with risk (HR: 0.90 [0.82-0.99]). The associations for BMI and BP differed between men and women (pinteraction ≤ 0.005). Among men, BMI, cholesterol and triglycerides were positively associated with risk for NMIBC (HRs: 1.09 [95% CI 1.01-1.18], 1.14 [1.02-1.25], and 1.30 [1.12-1.48] respectively), and BP was positively associated with MIBC (HR: 1.23 [1.02-1.49]). Among women, glucose was positively associated with MIBC (HR: 1.99 [1.04-3.81]). Apart from cholesterol, HRs for metabolic factors did not significantly differ between MIBC and NMIBC, and there were no interactions between smoking and metabolic factors on BC. Our study supports an involvement of metabolic aberrations in BC risk. Whilst some associations were significant only in certain sub-groups, there were generally no significant differences in associations by smoking or tumor invasiveness.


Assuntos
Fumar/efeitos adversos , Neoplasias da Bexiga Urinária/epidemiologia , Neoplasias da Bexiga Urinária/metabolismo , Adulto , Áustria/epidemiologia , Glicemia/análise , Pressão Sanguínea , Índice de Massa Corporal , Colesterol/sangue , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Invasividade Neoplásica , Noruega/epidemiologia , Modelos de Riscos Proporcionais , Estudos Prospectivos , Fatores de Risco , Índice de Gravidade de Doença , Fatores Sexuais , Suécia/epidemiologia , Triglicerídeos/sangue , Neoplasias da Bexiga Urinária/patologia
17.
Int J Cancer ; 143(7): 1632-1643, 2018 10 01.
Artigo em Inglês | MEDLINE | ID: mdl-29696642

RESUMO

Air pollution has been classified as carcinogenic to humans. However, to date little is known about the relevance for cancers of the stomach and upper aerodigestive tract (UADT). We investigated the association of long-term exposure to ambient air pollution with incidence of gastric and UADT cancer in 11 European cohorts. Air pollution exposure was assigned by land-use regression models for particulate matter (PM) below 10 µm (PM10 ), below 2.5 µm (PM2.5 ), between 2.5 and 10 µm (PMcoarse ), PM2.5 absorbance and nitrogen oxides (NO2 and NOX ) as well as approximated by traffic indicators. Cox regression models with adjustment for potential confounders were used for cohort-specific analyses. Combined estimates were determined with random effects meta-analyses. During average follow-up of 14.1 years of 305,551 individuals, 744 incident cases of gastric cancer and 933 of UADT cancer occurred. The hazard ratio for an increase of 5 µg/m3 of PM2.5 was 1.38 (95% CI 0.99; 1.92) for gastric and 1.05 (95% CI 0.62; 1.77) for UADT cancers. No associations were found for any of the other exposures considered. Adjustment for additional confounders and restriction to study participants with stable addresses did not influence markedly the effect estimate for PM2.5 and gastric cancer. Higher estimated risks of gastric cancer associated with PM2.5 was found in men (HR 1.98 [1.30; 3.01]) as compared to women (HR 0.85 [0.5; 1.45]). This large multicentre cohort study shows an association between long-term exposure to PM2.5 and gastric cancer, but not UADT cancers, suggesting that air pollution may contribute to gastric cancer risk.


Assuntos
Poluição do Ar/efeitos adversos , Neoplasias de Cabeça e Pescoço/epidemiologia , Neoplasias Gástricas/epidemiologia , Adulto , Europa (Continente)/epidemiologia , Feminino , Seguimentos , Neoplasias de Cabeça e Pescoço/etiologia , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Prognóstico , Estudos Prospectivos , Fatores de Risco , Neoplasias Gástricas/etiologia
18.
Wien Klin Wochenschr ; 130(3-4): 115-125, 2018 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-29383443

RESUMO

Chronic myelomonocytic leukaemia is a rare disease and data on the treatment are often extrapolated from myelodysplastic syndrome studies. Although several scores exist for the prognosis of overall survival in chronic myelomonocytic leukaemia, so far there is no designated score for the prediction of the time to first treatment. We tested clinical parameters and cytogenetic information for their ability to predict the time to first treatment in our single center cohort of 55 unselected consecutive chronic myelomonocytic leukaemia patients. In multivariate analysis we identified elevated lactate dehydrogenase (≥223 U/l), higher bone marrow blast percentage (≥7.5%) and thrombocytopenia (<55 G/l) at initial diagnosis as the most relevant parameters for the time to first treatment. Using these three parameters we developed a risk score that efficiently estimates the time to treatment initiation with azacitidine or hydroxyurea (p < 0.001; log-rank). In the high-risk group (≥2 risk factors) 85% of patients required treatment within 1 year, whereas this was the case in 48% in the intermediate-risk (1 risk factor) and in 0% in the low-risk group (0 risk factors). Our risk model was validated in an external test cohort of 65 patients and may serve as a simplified and easily applicable tool for identifying patients who may not require early treatment initiation.


Assuntos
Azacitidina/uso terapêutico , Hidroxiureia/uso terapêutico , Leucemia Mielomonocítica Crônica , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Leucemia Mielomonocítica Crônica/tratamento farmacológico , Masculino , Pessoa de Meia-Idade , Síndromes Mielodisplásicas , Prognóstico , Estudos Retrospectivos , Fatores de Tempo
19.
Leuk Lymphoma ; 59(5): 1121-1126, 2018 05.
Artigo em Inglês | MEDLINE | ID: mdl-28853315

RESUMO

According to former classification systems chronic myelomonocytic leukemia (CMML) is listed within myelodysplastic syndromes (MDS). Therefore data regarding treatment of CMML is largely derived from MDS trials. Two published studies suggest efficacy of lenalidomide in a proportion of patients with CMML, but the number of patients included was very low. We initiated this phase I trial with lenalidomide in patients with CMML. Primary objective of the current study was to determine the maximum tolerated dose (MTD). Secondary objectives were safety, tolerability and response. Twenty patients were enrolled and received lenalidomide using a classical 3 + 3 design. Lenalidomide 5 mg daily was confirmed as MTD. Best response achieved was partial remission in one patient and stable disease in nine patients. Lack of response with primary progressive disease was seen in three patients. Lenalidomide had a good toxicity profile in this study with thrombocytopenia being the main toxicity observed. Efficacy needs to be confirmed in further trials.


Assuntos
Inibidores da Angiogênese/uso terapêutico , Lenalidomida/uso terapêutico , Leucemia Mielomonocítica Crônica/tratamento farmacológico , Idoso , Idoso de 80 Anos ou mais , Feminino , Seguimentos , Humanos , Leucemia Mielomonocítica Crônica/patologia , Masculino , Dose Máxima Tolerável , Pessoa de Meia-Idade , Prognóstico , Taxa de Sobrevida
20.
Neuro Oncol ; 20(3): 420-432, 2018 02 19.
Artigo em Inglês | MEDLINE | ID: mdl-29016987

RESUMO

Background: Epidemiological evidence on the association between ambient air pollution and brain tumor risk is sparse and inconsistent. Methods: In 12 cohorts from 6 European countries, individual estimates of annual mean air pollution levels at the baseline residence were estimated by standardized land-use regression models developed within the ESCAPE and TRANSPHORM projects: particulate matter (PM) ≤2.5, ≤10, and 2.5-10 µm in diameter (PM2.5, PM10, and PMcoarse), PM2.5 absorbance, nitrogen oxides (NO2 and NOx) and elemental composition of PM. We estimated cohort-specific associations of air pollutant concentrations and traffic intensity with total, malignant, and nonmalignant brain tumor, in separate Cox regression models, adjusting for risk factors, and pooled cohort-specific estimates using random-effects meta-analyses. Results: Of 282194 subjects from 12 cohorts, 466 developed malignant brain tumors during 12 years of follow-up. Six of the cohorts also had data on nonmalignant brain tumor, where among 106786 subjects, 366 developed brain tumor: 176 nonmalignant and 190 malignant. We found a positive, statistically nonsignificant association between malignant brain tumor and PM2.5 absorbance (hazard ratio and 95% CI: 1.67; 0.89-3.14 per 10-5/m3), and weak positive or null associations with the other pollutants. Hazard ratio for PM2.5 absorbance (1.01; 0.38-2.71 per 10-5/m3) and all other pollutants were lower for nonmalignant than for malignant brain tumors. Conclusion: We found suggestive evidence of an association between long-term exposure to PM2.5 absorbance indicating traffic-related air pollution and malignant brain tumors, and no association with overall or nonmalignant brain tumors.


Assuntos
Poluição do Ar/efeitos adversos , Neoplasias Encefálicas/epidemiologia , Neoplasias Encefálicas/etiologia , Exposição Ambiental/efeitos adversos , Material Particulado/efeitos adversos , Adulto , Neoplasias Encefálicas/patologia , Estudos de Coortes , Europa (Continente)/epidemiologia , Feminino , Seguimentos , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Prognóstico , Fatores de Risco
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