RESUMO
Background: Occupational exposure to acrylamide was associated with excess mortality from pancreatic cancer, though in the absence of dose-risk relationship. Few epidemiological studies have examined the association between acrylamide from diet and pancreatic cancer risk. Patients and methods: We considered this issue in a combined set of 1975 cases of pancreatic cancer and 4239 controls enrolled in six studies of the Pancreatic Cancer Case-Control Consortium (PanC4). We calculated pooled odds ratios (ORs) and their 95% confidence intervals (CI) by estimating study-specific ORs through multivariate unconditional logistic regression models and pooling the obtained estimates using random-effects models. Results: Compared with the lowest level of estimated dietary acrylamide intake, the pooled ORs were 0.97 (95% CI, 0.79-1.19) for the second, 0.91 (95% CI, 0.71-1.16) for the third, and 0.92 (95% CI, 0.66-1.28) for the fourth (highest) quartile of intake. For an increase of 10 µg/day of acrylamide intake, the pooled OR was 0.96 (95% CI, 0.87-1.06), with heterogeneity between estimates (I2 = 67%). Results were similar across various subgroups, and were confirmed when using a one-stage modelling approach. Conclusions: This PanC4 pooled-analysis found no association between dietary acrylamide and pancreatic cancer.
Assuntos
Acrilamida/efeitos adversos , Dieta/efeitos adversos , Neoplasias Pancreáticas/etiologia , Estudos de Casos e Controles , Humanos , Fatores de RiscoRESUMO
BACKGROUND: The potential role of vitamin D in the aetiology of pancreatic cancer is unclear, with recent studies suggesting both positive and negative associations. PATIENTS AND METHODS: We used data from nine case-control studies from the International Pancreatic Cancer Case-Control Consortium (PanC4) to examine associations between pancreatic cancer risk and dietary vitamin D intake. Study-specific odds ratios (ORs) were estimated using multivariable logistic regression, and ORs were then pooled using a random-effects model. From a subset of four studies, we also calculated pooled estimates of association for supplementary and total vitamin D intake. RESULTS: Risk of pancreatic cancer increased with dietary intake of vitamin D [per 100 international units (IU)/day: OR = 1.13, 95% confidence interval (CI) 1.07-1.19, P = 7.4 × 10(-6), P-heterogeneity = 0.52; ≥230 versus <110 IU/day: OR = 1.31, 95% CI 1.10-1.55, P = 2.4 × 10(-3), P-heterogeneity = 0.81], with the association possibly stronger in people with low retinol/vitamin A intake. CONCLUSION: Increased risk of pancreatic cancer was observed with higher levels of dietary vitamin D intake. Additional studies are required to determine whether or not our finding has a causal basis.
Assuntos
Adenocarcinoma/epidemiologia , Neoplasias Pancreáticas/induzido quimicamente , Vitamina D/administração & dosagem , Vitamina D/efeitos adversos , Vitaminas/administração & dosagem , Vitaminas/efeitos adversos , Adulto , Idoso , Idoso de 80 Anos ou mais , Estudos de Casos e Controles , Diabetes Mellitus/epidemiologia , Dieta/estatística & dados numéricos , Suplementos Nutricionais , Feminino , Humanos , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Obesidade/epidemiologia , Razão de Chances , Neoplasias Pancreáticas/epidemiologia , Pancreatite/epidemiologia , Fatores de RiscoRESUMO
BACKGROUND: Type 2 diabetes mellitus has been associated with an excess risk of pancreatic cancer, but the magnitude of the risk and the time-risk relationship are unclear, and there is limited information on the role of antidiabetic medications. PATIENTS AND METHODS: We analyzed individual-level data from 15 case-control studies within the Pancreatic Cancer Case-Control Consortium, including 8305 cases and 13 987 controls. Pooled odds ratios (ORs) were estimated from multiple logistic regression models, adjusted for relevant covariates. RESULTS: Overall, 1155 (15%) cases and 1087 (8%) controls reported a diagnosis of diabetes 2 or more years before cancer diagnosis (or interview, for controls), corresponding to an OR of 1.90 (95% confidence interval, CI, 1.72-2.09). Consistent risk estimates were observed across strata of selected covariates, including body mass index and tobacco smoking. Pancreatic cancer risk decreased with duration of diabetes, but a significant excess risk was still evident 20 or more years after diabetes diagnosis (OR 1.30, 95% CI 1.03-1.63). Among diabetics, long duration of oral antidiabetic use was associated with a decreased pancreatic cancer risk (OR 0.31, 95% CI 0.14-0.69, for ≥15 years). Conversely, insulin use was associated with a pancreatic cancer risk in the short term (OR 5.60, 95% CI 3.75-8.35, for <5 years), but not for longer duration of use (OR 0.95, 95% CI 0.53-1.70, for ≥15 years). CONCLUSION: This study provides the most definitive quantification to date of an excess risk of pancreatic cancer among diabetics. It also shows that a 30% excess risk persists for more than two decades after diabetes diagnosis, thus supporting a causal role of diabetes in pancreatic cancer. Oral antidiabetics may decrease the risk of pancreatic cancer, whereas insulin showed an inconsistent duration-risk relationship.
Assuntos
Diabetes Mellitus Tipo 2/complicações , Hipoglicemiantes/uso terapêutico , Neoplasias Pancreáticas/epidemiologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Estudos de Casos e Controles , Diabetes Mellitus Tipo 2/tratamento farmacológico , Diabetes Mellitus Tipo 2/epidemiologia , Diabetes Mellitus Tipo 2/patologia , Feminino , Humanos , Insulina , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Neoplasias Pancreáticas/tratamento farmacológico , Neoplasias Pancreáticas/etiologia , Neoplasias Pancreáticas/patologia , Fatores de Risco , FumarRESUMO
BACKGROUND: Non-Hodgkin lymphoma (NHL) subtypes, diffuse large B-cell (DLBCL) and follicular lymphoma (FL) have different sex ratios and are diagnosed at ages over 60 years; DLBCL is more common in men and diagnosed at older ages than FL, which occurs more among women. This analysis of postmenopausal women examines the relationship between postmenopausal hormone therapy and NHL. DESIGN: Self-reported use of postmenopausal hormone therapy from 2094 postmenopausal women with NHL and 2731 without were pooled across nine case-control studies (1983-2005) from North America, Europe and Japan. Study-specific odds ratios (OR) and 95% confidence intervals (CI) estimated using logistic regression were pooled using random-effects meta-analyses. RESULTS: Postmenopausal women who used hormone therapy were at decreased risk of NHL (pooled OR = 0.79, 95% CI 0.69-0.90). Risks were reduced when the age of starting was 50 years or older. There was no clear trend with number of years of use. Current users were at decreased risk while those stopping over 2 years before diagnosis were not. Having a hysterectomy or not did not affect the risk. Favourable effects were present for DLBCL (pooled OR = 0.66, 95% CI 0.54-0.80) and FL (pooled OR = 0.82, 95% CI 0.66-1.01). CONCLUSION: Postmenopausal hormone therapy, particularly used close to menopause, is associated with a decreased risk of NHL.
Assuntos
Terapia de Reposição de Estrogênios , Linfoma Folicular/epidemiologia , Linfoma Difuso de Grandes Células B/epidemiologia , Idoso , Estudos de Casos e Controles , Feminino , Humanos , Histerectomia , Masculino , Pessoa de Meia-Idade , Pós-Menopausa , RiscoRESUMO
BACKGROUND: Peptic ulcer and its treatments have been associated to pancreatic cancer risk, although the evidence is inconsistent. METHODS: We pooled 10 case-control studies within the Pancreatic Cancer Case-control Consortium (PanC4), including 4717 pancreatic cancer cases and 9374 controls, and estimated summary odds ratios (OR) using multivariable logistic regression models. RESULTS: The OR for pancreatic cancer was 1.10 [95% confidence interval (CI) 0.98-1.23] for history of ulcer (OR = 1.08 for gastric and 0.97 for duodenal ulcer). The association was stronger for a diagnosis within 2 years before cancer diagnosis (OR = 2.43 for peptic, 1.75 for gastric, and 1.98 for duodenal ulcer). The OR was 1.53 (95% CI 1.15-2.03) for history of gastrectomy; however, the excess risk was limited to a gastrectomy within 2 years before cancer diagnosis (OR = 6.18, 95% CI 1.82-20.96), while no significant increased risk was observed for longer time since gastrectomy. No associations were observed for pharmacological treatments for ulcer, such as antacids, H2-receptor antagonists, or proton-pump inhibitors. CONCLUSIONS: This uniquely large collaborative study does not support the hypothesis that peptic ulcer and its treatment materially affect pancreatic cancer risk. The increased risk for short-term history of ulcer and gastrectomy suggests that any such association is due to increased cancer surveillance.
Assuntos
Gastroenteropatias/patologia , Neoplasias Pancreáticas/patologia , Úlcera/patologia , Idoso , Estudos de Casos e Controles , Feminino , Gastrectomia/efeitos adversos , Gastroenteropatias/complicações , Gastroenteropatias/epidemiologia , Gastroenteropatias/cirurgia , Humanos , Modelos Logísticos , Pessoa de Meia-Idade , Neoplasias Pancreáticas/complicações , Neoplasias Pancreáticas/epidemiologia , Fatores de Risco , Úlcera/complicações , Úlcera/epidemiologia , Úlcera/cirurgiaRESUMO
Non-Hodgkin lymphoma (NHL) has been associated with immunological defects, chronic inflammatory and autoimmune conditions. Given the link between immune dysfunction and NHL, genetic variants in toll-like receptors (TLRs) have been regarded as potential predictive factors of susceptibility to NHL. Adequate anti-tumoral responses are known to depend on TLR9 function, such that the use of its synthetic ligand is being targeted as a therapeutic strategy. We investigated the association between the functional rs5743836 polymorphism in the TLR9 promoter and risk for B-cell NHL and its major subtypes in three independent case-control association studies from Portugal (1160 controls, 797 patients), Italy (468 controls, 494 patients) and the US (972 controls, 868 patients). We found that the rs5743836 polymorphism was significantly overtransmitted in both Portuguese (odds ratio (OR), 1.85; P=7.3E-9) and Italian (OR, 1.84; P=6.0E-5) and not in the US cohort of NHL patients. Moreover, the increased transcriptional activity of TLR9 in mononuclear cells from patients harboring rs5743836 further supports a functional effect of this polymorphism on NHL susceptibility in a population-dependent manner.
Assuntos
Linfoma não Hodgkin/genética , Polimorfismo Genético , Receptor Toll-Like 9/genética , Feminino , Genética Populacional , Humanos , Linfoma não Hodgkin/epidemiologia , Masculino , Pessoa de Meia-Idade , Fatores de RiscoRESUMO
BACKGROUND: Pancreatitis is a known risk factor for pancreatic cancer; however, an unknown fraction of the disease is thought to be a consequence of tumor-related duct obstruction. PATIENTS AND METHODS: A pooled analysis of a history of pancreatitis and risk of pancreatic cancer was carried out considering the time interval between diagnoses and potential modification by covariates. Adjusted pooled odds ratios (ORs) and 95% confidence intervals (CIs) were estimated from 10 case-control studies (5048 cases of ductal pancreatic adenocarcinoma and 10,947 controls) taking part in the International Pancreatic Cancer Case-Control Consortium (PanC4). RESULTS: The association between pancreatitis and pancreatic cancer was nearly three-fold at intervals of >2 years between diagnoses (OR: 2.71, 95% CI: 1.96-3.74) and much stronger at intervals of ≤2 years (OR: 13.56, 95% CI: 8.72-21.90) probably reflecting a combination of reverse causation and antecedent misdiagnosis of pancreas cancer as pancreatitis. The younger (<65 years) pancreatic cancer cases showed stronger associations with previous (>2 years) pancreatitis (OR: 3.91, 95% CI: 2.53-6.04) than the older (≥65 years) cases (OR: 1.68, 95% CI: 1.02-2.76; P value for interaction: 0.006). CONCLUSIONS: Despite a moderately strong association between pancreatitis (diagnosed before >2 years) and pancreatic cancer, the population attributable fraction was estimated at 1.34% (95% CI: 0.612-2.07%), suggesting that a relatively small proportion of pancreatic cancer might be avoided if pancreatitis could be prevented.
Assuntos
Neoplasias Pancreáticas/epidemiologia , Neoplasias Pancreáticas/etiologia , Pancreatite/complicações , Adenocarcinoma/epidemiologia , Adenocarcinoma/etiologia , Idoso , Consumo de Bebidas Alcoólicas/efeitos adversos , Estudos de Casos e Controles , Complicações do Diabetes , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Razão de Chances , Pancreatite/etiologia , Fatores de Risco , Fumar/efeitos adversosRESUMO
BACKGROUND: The two most common forms of non-Hodgkin lymphoma (NHL) exhibit different sex ratios: diffuse large B-cell lymphoma (DLBCL) occurs more frequently in men and follicular lymphoma (FL) more frequently in women. Looking among women alone, this pooled analysis explores the relationship between reproductive histories and these cancers. MATERIALS AND METHODS: Self-reported reproductive histories from 4263 women with NHL and 5971 women without NHL were pooled across 18 case-control studies (1983-2005) from North America, Europe and Japan. Study-specific odd ratios (ORs) and confidence intervals (CIs) were estimated using logistic regression and pooled using random-effects meta-analyses. RESULTS: Associations with reproductive factors were found for FL rather than NHL overall and DLBCL. In particular, the risk of FL decreased with increasing number of pregnancies (pooled OR(trend) = 0.88, 95% CI 0.81-0.96). FL was associated with hormonal contraception (pooled OR = 1.30, 95% CI 1.04-1.63), and risks were increased when use started after the age of 21, was used for <5 years or stopped for >20 years before diagnosis. DLBCL, on the other hand, was not associated with hormonal contraception (pooled OR = 0.87, 95% CI 0.65-1.16). CONCLUSIONS: Hormonal contraception is associated with an increased risk of FL but not of DLBCL or NHL overall.
Assuntos
Anticoncepcionais Orais Hormonais/efeitos adversos , Linfoma não Hodgkin/etiologia , Inibição da Ovulação , História Reprodutiva , Estudos de Casos e Controles , Anticoncepcionais Orais Hormonais/administração & dosagem , Feminino , Humanos , Modelos Logísticos , Linfoma não Hodgkin/fisiopatologia , Razão de Chances , Fenômenos Reprodutivos FisiológicosRESUMO
BACKGROUND: Heavy alcohol drinking has been related to pancreatic cancer, but the issue is still unsolved. METHODS: To evaluate the role of alcohol consumption in relation to pancreatic cancer, we conducted a pooled analysis of 10 case-control studies (5585 cases and 11,827 controls) participating in the International Pancreatic Cancer Case-Control Consortium. We computed pooled odds ratios (ORs) by estimating study-specific ORs adjusted for selected covariates and pooling them using random effects models. RESULTS: Compared with abstainers and occasional drinkers (< 1 drink per day), we observed no association for light-to-moderate alcohol consumption (≤ 4 drinks per day) and pancreatic cancer risk; however, associations were above unity for higher consumption levels (OR = 1.6, 95% confidence interval 1.2-2.2 for subjects drinking ≥ 9 drinks per day). Results did not change substantially when we evaluated associations by tobacco smoking status, or when we excluded participants who reported a history of pancreatitis, or participants whose data were based upon proxy responses. Further, no notable differences in pooled risk estimates emerged across strata of sex, age, race, study type, and study area. CONCLUSION: This collaborative-pooled analysis provides additional evidence for a positive association between heavy alcohol consumption and the risk of pancreatic cancer.
Assuntos
Consumo de Bebidas Alcoólicas/efeitos adversos , Neoplasias Pancreáticas/epidemiologia , Adulto , Idoso , Estudos de Casos e Controles , Fatores de Confusão Epidemiológicos , Feminino , Humanos , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Razão de Chances , Neoplasias Pancreáticas/etiologia , Pancreatite/complicações , Fatores de Risco , Fumar/efeitos adversosRESUMO
BACKGROUND: To evaluate the dose-response relationship between cigarette smoking and pancreatic cancer and to examine the effects of temporal variables. METHODS: We analyzed data from 12 case-control studies within the International Pancreatic Cancer Case-Control Consortium (PanC4), including 6507 pancreatic cases and 12 890 controls. We estimated summary odds ratios (ORs) by pooling study-specific ORs using random-effects models. RESULTS: Compared with never smokers, the OR was 1.2 (95% confidence interval [CI] 1.0-1.3) for former smokers and 2.2 (95% CI 1.7-2.8) for current cigarette smokers, with a significant increasing trend in risk with increasing number of cigarettes among current smokers (OR=3.4 for ≥35 cigarettes per day, P for trend<0.0001). Risk increased in relation to duration of cigarette smoking up to 40 years of smoking (OR=2.4). No trend in risk was observed for age at starting cigarette smoking, whereas risk decreased with increasing time since cigarette cessation, the OR being 0.98 after 20 years. CONCLUSIONS: This uniquely large pooled analysis confirms that current cigarette smoking is associated with a twofold increased risk of pancreatic cancer and that the risk increases with the number of cigarettes smoked and duration of smoking. Risk of pancreatic cancer reaches the level of never smokers â¼20 years after quitting.
Assuntos
Neoplasias Pancreáticas/etiologia , Fumar/efeitos adversos , Estudos de Casos e Controles , Humanos , Modelos Logísticos , Análise Multivariada , Razão de Chances , Sensibilidade e EspecificidadeRESUMO
Follicular lymphoma (FL) is an indolent, sometimes, fatal disease characterized by recurrence at progressively shorter intervals and is frequently refractive to therapy. Genome-wide association studies have identified single nucleotide polymorphisms (SNPs) in the human leukocyte antigen (HLA) region on chromosome 6p21.32-33 that are statistically significantly associated with FL risk. Low to medium resolution typing of single or multiple HLA genes has provided an incomplete picture of the total genetic risk imparted by this highly variable region. To gain further insight into the role of HLA alleles in lymphomagenesis and to investigate the independence of validated SNPs and HLA alleles with FL risk, high-resolution HLA typing was conducted using next-generation sequencing in 222 non-Hispanic White FL cases and 220 matched controls from a larger San Francisco Bay Area population-based case-control study of lymphoma. A novel protective association was found between the DPB1*03:01 allele and FL risk [odds ratio (OR) = 0.39, 95% confidence interval (CI) = 0.21-0.68]. Extended haplotypes DRB1*01:01-DQA1*01:01-DQB1*05:01 (OR = 2.01, 95% CI = 1.22-3.38) and DRB1*15-DQA1*01-DQB1*06 (OR = 0.55, 95% CI = 0.36-0.82) also influenced FL risk. Moreover, DRB1*15-DQA1*01-DQB1*06 was highly correlated with an established FL risk locus, rs2647012. These results provide further insight into the critical roles of HLA alleles and SNPs in FL pathogenesis that involve multi-locus effects across the HLA region.
Assuntos
Alelos , Predisposição Genética para Doença , Antígenos de Histocompatibilidade Classe II/genética , Antígenos de Histocompatibilidade Classe I/genética , Linfoma Folicular/genética , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Haplótipos , Humanos , Masculino , Pessoa de Meia-IdadeRESUMO
BACKGROUND: Cigarette smoking is the best-characterized risk factor for pancreatic cancer. However, data are limited for other tobacco smoking products and smokeless tobacco. MATERIALS AND METHODS: We conducted a pooled analysis of cigar and pipe smoking and smokeless tobacco use and risk of pancreatic cancer using data from 11 case-control studies (6056 cases and 11,338 controls) within the International Pancreatic Cancer Case-Control Consortium (PanC4). Pooled odds ratios (OR) and the corresponding 95% confidence intervals (CI) were estimated by unconditional multiple logistic regression models adjusted for study center and selected covariates. RESULTS: Compared with never tobacco users, the OR for cigar-only smokers was 1.6 (95% CI: 1.2-2.3), i.e. comparable to that of cigarette-only smokers (OR 1.5; 95% CI 1.4-1.6). The OR was 1.1 (95% CI 0.69-1.6) for pipe-only smokers. There was some evidence of increasing risk with increasing amount of cigar smoked per day (OR 1.82 for ≥ 10 grams of tobacco), although not with duration. The OR for ever smokeless tobacco users as compared with never tobacco users was 0.98 (95% CI 0.75-1.3). CONCLUSION: This collaborative analysis provides evidence that cigar smoking is associated with an excess risk of pancreatic cancer, while no significant association emerged for pipe smoking and smokeless tobacco use.
Assuntos
Neoplasias Pancreáticas/etiologia , Fumar/efeitos adversos , Tabaco sem Fumaça/efeitos adversos , Adulto , Idoso , Idoso de 80 Anos ou mais , Estudos de Casos e Controles , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Risco , TabagismoRESUMO
Many effective options exist to accurately type DNA for human leukocyte antigen (HLA) alleles. However, most of the existing methods are excessively costly in terms of overall monetary costs, DNA requirements, and proprietary software. We present a novel assay capable of resolving heterozygous HLA-DQB1 allelotypes at two digits, with even greater specificity for the HLA-DQB1*06 allele family, by using the multiplexed ligation-dependent probe amplification technology. This assay provides more specific allele data than genome-wide analysis and is more affordable than sequencing, making it a useful intermediate for researchers seeking to accurately allelotype human DNA samples.
Assuntos
Alelos , Cadeias beta de HLA-DQ/genética , Teste de Histocompatibilidade/métodos , Reação em Cadeia da Ligase/métodos , Sondas de Oligonucleotídeos/química , Linhagem Celular , Feminino , Heterozigoto , Teste de Histocompatibilidade/economia , Humanos , Reação em Cadeia da Ligase/economia , MasculinoRESUMO
Nineteen counties from San Francisco and Los Angeles, California and Seattle, Washington were the United States sites for a large population-based case-control study of childhood brain tumors (CBTs), sponsored by the National Cancer Institute. CBT patients who were < 20 years of age and were diagnosed between 1984 and 1991 were reported to each region's cancer registry. The 801 control subjects were obtained by random digit dial and were frequency-matched to the 540 CBT patients in San Francisco and Seattle (one patient to two controls) and in Los Angeles (one patient to one control). Data collected by in-person interview with subjects' mothers were analyzed to investigate an association between risk for CBTs and life on a farm, exposure to farm animals (dairy cattle, beef cattle, pigs, sheep/goats, poultry, and horses), and some cat and non-farm horse exposures. Elevated risks for CBTs were observed in association with mothers' exposure to pigs [odds ratio (OR) = 3.8, 95% confidence interval (CI) = 1.2-12] and horses (OR = 2.2, 95% CI = 1.0-4.8) on a farm during the index pregnancy. Children diagnosed with primitive neuroectodermal tumors showed elevated risks for CBTs with personal and maternal prenatal exposure to pigs (child, OR = 4.0, 95% CI = 1.2-13; mother, OR = 11.9, 95% CI = 2.8-51) and poultry (child, OR = 3.0, 95% CI = 1.1-8.0; mother, OR = 4.0, 95% CI = 1.2-14). No other animal exposures of children or mothers were found to be consistently related to CBTs. Children diagnosed with primitive neuroectodermal tumors who were on a farm for > 1 year and were first on a farm when they were < 6 months of age also had increased risk for CBTs (OR = 3.9, 95% CI = 1.2-13). A somewhat increased risk for CBTs was found for children of mothers who ever had worked on livestock farms compared with mothers who never had worked on a farm (OR = 7.4, 95% CI = 0.86-64, based on five case mothers and one control mother who worked on livestock farms during the 5 years preceding the birth of the index child). The associations are consistent with those of two previous studies in Norway (P. Kristensen et al., Int. J. Cancer, 65: 39-50, 1996) and the United States and Canada (G. R. Bunin et al., Cancer Epidemiol. Biomark. Prev., 3: 197-204, 1994) that investigated the role of farm-related exposures in the etiology of CBTs.
Assuntos
Agricultura , Neoplasias Encefálicas/etiologia , Exposição Ambiental , Exposição Ocupacional , Adolescente , Adulto , Animais , Animais Domésticos , Astrócitos/patologia , Neoplasias Encefálicas/epidemiologia , Gatos , Bovinos , Criança , Pré-Escolar , Feminino , Cavalos , Humanos , Lactente , Masculino , Tumores Neuroectodérmicos Primitivos/etiologia , Gravidez , Efeitos Tardios da Exposição Pré-Natal , Estados Unidos/epidemiologiaRESUMO
Data from a large, population-based case-control study were analyzed to investigate the relationship between prenatal exposure to tobacco smoke and childhood brain tumors (CBTs). A total of 540 CBT patients, diagnosed between 1984 and 1991, were identified from population-based tumor registries in 19 West Coast counties that included Seattle, WA (13 counties), San Francisco, CA (5 counties), and Los Angeles, CA (1 county). Random digit dial was used to select 801 control subjects from the three geographical regions to obtain a case:control ratio of 1:2 in San Francisco and Seattle and 1:1 in Los Angeles. The data first were analyzed separately by geographical site and then were combined with adjustments made for gender, age at the time of diagnosis (or reference date of control subjects), birth year of the index child, and maternal race. No association was found between the risk of CBTs and maternal or paternal smoking before pregnancy and there was no association between CBTs and maternal smoking during pregnancy [odds ratio (OR) = 0.98; 95% confidence interval (CI) = 0.72-1.3]. A slightly increased OR for CBTs was found for paternal smoking during pregnancy in the absence of maternal smoking (OR = 1.2; 95% CI = 0.90-1.5) and for maternal exposure to passive smoke from any source (OR = 1.2; 95% CI = 0.95-1.6). The results of this analysis are consistent with results from several prior epidemiological studies that showed no significant association between CBTs and maternal smoking before or during pregnancy or maternal exposure to passive smoke during pregnancy.
Assuntos
Neoplasias Encefálicas/etiologia , Efeitos Tardios da Exposição Pré-Natal , Fumar/efeitos adversos , Adolescente , Adulto , Fatores Etários , Povo Asiático , População Negra , Estudos de Casos e Controles , Criança , Pré-Escolar , Intervalos de Confiança , Pai , Feminino , Humanos , Lactente , Recém-Nascido , Los Angeles , Masculino , Mães , Vigilância da População , Gravidez , Complicações na Gravidez , Sistema de Registros , São Francisco , Fatores Sexuais , Poluição por Fumaça de Tabaco/efeitos adversos , Estados Unidos , Washington , População BrancaRESUMO
Occupational exposure to p,p'-dichlorodiphenyltrichloroethane (DDT) has been associated with increased pancreatic cancer risk. We measured organochlorine levels in serum obtained at the study enrollment from 108 pancreatic cancer cases and 82 control subjects aged 32-85 years in the San Francisco Bay Area between 1996 and 1998. Cases were identified using rapid case-ascertainment methods; controls were frequency-matched to cases on age and sex via random digit dial and random sampling of Health Care Financing Administration lists. Serum organochlorine levels were adjusted for lipid content to account for variation in the lipid concentration in serum between subjects. Median concentrations of p,p'-dichlorodiphenyldichloroethylene (DDE, 1290 versus 1030 ng/g lipid; P = 0.05), polychlorinated biphenyls (PCBs; 330 versus 220 ng/g lipid; P<0.001), and transnonachlor (54 versus 28 ng/g lipid; P = 0.03) were significantly greater among cases than controls. A significant dose-response relationship was observed for total PCBs (P for trend <0.001). Subjects in the highest tertile of PCBs (> or =360 ng/g lipid) had an odds ratio (OR) of 4.2 [95% confidence interval (CI) = 1.8-9.4] compared to the lowest tertile. The OR of 2.1 for the highest level of p,p'-DDE (95% CI = 0.9-4.7) diminished (OR = 1.1; 95% CI = 0.4-2.8) when PCBs were included in the model. Because pancreatic cancer is characterized by cachexia, the impact of this on the serum organochlorine levels in cases is difficult to predict. One plausible effect of cachexia is bioconcentration of organochlorines in the diminished lipid pool, which would lead to a bias away from the null. To explore this, a sensitivity analysis was performed assuming a 10-40% bioconcentration of organochlorines in case samples. The OR associated with PCBs remained elevated under conditions of up to 25% bioconcentration.
Assuntos
Hidrocarbonetos Clorados , Inseticidas/efeitos adversos , Neoplasias Pancreáticas/etiologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Caquexia , Estudos de Casos e Controles , Relação Dose-Resposta a Droga , Feminino , Humanos , Inseticidas/sangue , Masculino , Pessoa de Meia-Idade , Exposição Ocupacional , Neoplasias Pancreáticas/epidemiologia , Neoplasias Pancreáticas/fisiopatologia , Fatores de RiscoRESUMO
Pancreatic cancer is a highly fatal cancer with few identified risk factors. Increased risk of pancreatic cancer in tobacco smokers and among diabetic patients is well established, and some reports have suggested associations with coffee consumption and occupational exposure to organochlorines. At present, there is little information regarding the possible association of these risk factors with the known genetic alterations found in pancreatic cancers, such as activation of the K-ras oncogene and inactivation of the p53 tumor suppressor gene. Knowledge of such relationships may help to understand the molecular pathways of pancreatic tumorigenesis. We investigated the association between these molecular defects and risk factors for pancreatic cancer in 61 newly diagnosed patients identified through an ongoing study of pancreatic cancer in the San Francisco Bay Area. Interview information was obtained regarding environmental exposures, medical history, and demographic factors. Serum levels of dichlorodiphenyltrichloroethylene (DDE) and polychlorinated biphenyls were available on a subset of 24 patients. Tumor blocks were located from local hospitals and used for K-ras mutational analysis at codon 12 and for p53 protein immunohistochemistry. The molecular analyses were facilitated through the use of laser capture microdissection, which provides a reliable method to obtain almost pure populations of tumor cells. Mutations in K-ras codon 12 were found in 46 (75%) of 61 pancreatic cancers. A prior diagnosis of diabetes was significantly associated with K-ras negative tumors (P = 0.002, Fisher's exact test). The absence of this mutation was also associated with increased serum levels of DDE, although this association was not statistically significant (P = 0.16, Wilcoxon's test). There was no difference in polychlorinated biphenyl levels between the K-ras wild-type and mutant groups. Immunohistochemical staining for p53 protein did not differ by patient characteristics or clinical history, but significant associations were found with poor glandular differentiation (P = 0.002, chi2 trend test), severe nuclear atypia (P = 0.0007, chi2 trend test), and high tumor grade (P = 0.004, chi2 trend test). Our results are suggestive of the presence of K-ras codon 12 mutation-independent tumorigenesis pathways in patients with prior diabetes and possibly in patients with higher serum levels of DDE. Our results also support a role for the p53 tumor suppressor protein in the maintenance of genomic integrity.
Assuntos
Carcinógenos/efeitos adversos , Exposição Ambiental , Genes p53/genética , Genes ras/genética , Neoplasias Pancreáticas/genética , Idoso , Estudos de Casos e Controles , Análise Mutacional de DNA , Complicações do Diabetes , Diclorodifenil Dicloroetileno/efeitos adversos , Feminino , Humanos , Imuno-Histoquímica , Inseticidas/efeitos adversos , Masculino , Anamnese , Pessoa de Meia-Idade , Neoplasias Pancreáticas/etiologia , Fatores de RiscoRESUMO
Thrombolysis with tissue plasminogen activator (tPA) and hypothermia are two potential treatment modalities for acute ischemic stroke. Many investigators are studying these modalities both in the laboratory and in clinical trials. Because these modalities each appear to show benefit in animal models, there is considerable interest in studying combined therapy with both thrombolysis and hypothermia. However, it is known that alterations in the coagulation system can occur with decreased body temperature. Clinicians have frequently observed bleeding problems when patients are subjected to hypothermia for a variety of reasons. Hypothermia induced coagulopathy has been attributed to a variety of factors. Hypothermia can cause platelet dysfunction, inhibition of clotting factors, increased fibrinolysis and endogenous production of a heparin-like factor. Groups who studied fibrinolysis and temperature, however, found the opposite to be the case. Clot lysis studies with streptokinase showed increased fibrinolysis at higher temperatures. Data by Mumme suggested that the peak fibrinolytic activity of streptokinase was at 40 degrees C, but at 43 degrees C fibrinolytic activity was decreased. Rijken et al studied plasminogen activation with tissue plasminogen activator (tPA), urokinase and streptokinase at extremely low temperatures. They found less plasminogen activation and fibrinogen degradation at 25 degrees C compared to 37 degrees C, but negligible differences at 10 degrees C, 0 degrees C and -8 degrees C. To our knowledge, there is no data studying the fibrinolytic activity of tissue plasminogen activator (tPA) at temperature ranges between 25-37 degrees C which is the range of temperatures used clinically for therapeutic purposes.(ABSTRACT TRUNCATED AT 250 WORDS)