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1.
Artigo em Inglês | MEDLINE | ID: mdl-33827984

RESUMO

BACKGROUND: Given the increased use and diversity of diagnostic procedures, it is important to understand genetic susceptibility to radiation-induced thyroid cancer. METHODS: Based on self-declared diagnostic radiology examination records in addition to existing literature, we estimated the radiation dose delivered to the thyroid gland from diagnostic procedures during childhood and adulthood in two case-control studies conducted in France. A total of 1071 differentiated thyroid cancer (DTC) cases and 1188 controls from the combined studies were genotyped using a custom-made Illumina OncoArray DNA chip. We focused our analysis on variants in genes involved in DNA damage response and repair pathways, representing a total of 5817 single-nucleotide polymorphisms in 571 genes. We estimated the odds ratio per milli-Gray (OR/mGy) of the radiation dose delivered to the thyroid gland using conditional logistic regression. We then used an unconditional logistic regression model to assess the association between DNA repair gene variants and DTC risk. We performed a meta-analysis of the two studies. RESULTS: The OR/mGy was 1.02 (95% CI: 1.00, 1.03). We found significant associations between DTC and rs7164173 in CHD2 (p = 5.79 10-5), rs6067822 in NFATc2 (p = 9.26 10-5), rs1059394 and rs699517 both in ENOSF1/THYS, rs12702628 in RPA3, and an interaction between rs7068306 in MGMT and thyroid radiation doses (p= 3.40 10-4). CONCLUSIONS: Our results suggest a role for variants in CDH2, NFATc2, ENOSF1/THYS, RPA3 and MGMT in DTC risk. IMPACT: CDH2, NFATc2, ENOSF1/THYS and RPA3 have not previously been shown to be associated with DTC risk.

2.
Int J Cancer ; 2021 Feb 02.
Artigo em Inglês | MEDLINE | ID: mdl-33527407

RESUMO

Incidence of differentiated thyroid carcinoma (DTC) varies considerably between ethnic groups, with particularly high incidence rates in Pacific Islanders. DTC is one of the cancers with the highest familial risk suggesting a major role of genetic risk factors, but only few susceptibility loci were identified so far. In order to assess the contribution of known DTC susceptibility loci and to identify new ones, we conducted a multiethnic genome-wide association study (GWAS) in individuals of European ancestry and of Oceanian ancestry from Pacific Islands. Our study included 1554 cases/1973 controls of European ancestry and 301 cases/348 controls of Oceanian ancestry from seven population-based case-control studies participating to the EPITHYR consortium. All participants were genotyped using the OncoArray-500K Beadchip (Illumina). We confirmed the association with the known DTC susceptibility loci at 2q35, 8p12, 9q22.33 and 14q13.3 in the European ancestry population and suggested two novel signals at 1p31.3 and 16q23.2, which were associated with thyroid-stimulating hormone levels in previous GWAS. We additionally replicated an association with 5p15.33 reported previously in Chinese and European populations. Except at 1p31.3, all associations were in the same direction in the population of Oceanian ancestry. We also observed that the frequencies of risk alleles at 2q35, 5p15.33 and 16q23.2 were significantly higher in Oceanians than in Europeans. However, additional GWAS and epidemiological studies in Oceanian populations are needed to fully understand the highest incidence observed in these populations.

3.
Cancer Epidemiol Biomarkers Prev ; 30(4): 623-642, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-33500318

RESUMO

BACKGROUND: It is not known whether modifiable lifestyle factors that predict survival after invasive breast cancer differ by subtype. METHODS: We analyzed data for 121,435 women diagnosed with breast cancer from 67 studies in the Breast Cancer Association Consortium with 16,890 deaths (8,554 breast cancer specific) over 10 years. Cox regression was used to estimate associations between risk factors and 10-year all-cause mortality and breast cancer-specific mortality overall, by estrogen receptor (ER) status, and by intrinsic-like subtype. RESULTS: There was no evidence of heterogeneous associations between risk factors and mortality by subtype (P adj > 0.30). The strongest associations were between all-cause mortality and BMI ≥30 versus 18.5-25 kg/m2 [HR (95% confidence interval (CI), 1.19 (1.06-1.34)]; current versus never smoking [1.37 (1.27-1.47)], high versus low physical activity [0.43 (0.21-0.86)], age ≥30 years versus <20 years at first pregnancy [0.79 (0.72-0.86)]; >0-<5 years versus ≥10 years since last full-term birth [1.31 (1.11-1.55)]; ever versus never use of oral contraceptives [0.91 (0.87-0.96)]; ever versus never use of menopausal hormone therapy, including current estrogen-progestin therapy [0.61 (0.54-0.69)]. Similar associations with breast cancer mortality were weaker; for example, 1.11 (1.02-1.21) for current versus never smoking. CONCLUSIONS: We confirm associations between modifiable lifestyle factors and 10-year all-cause mortality. There was no strong evidence that associations differed by ER status or intrinsic-like subtype. IMPACT: Given the large dataset and lack of evidence that associations between modifiable risk factors and 10-year mortality differed by subtype, these associations could be cautiously used in prognostication models to inform patient-centered care.

4.
Int J Cancer ; 148(8): 1895-1909, 2021 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-33368296

RESUMO

Single-nucleotide polymorphisms (SNPs) in over 180 loci have been associated with breast cancer (BC) through genome-wide association studies involving mostly unselected population-based case-control series. Some of them modify BC risk of women carrying a BRCA1 or BRCA2 (BRCA1/2) mutation and may also explain BC risk variability in BC-prone families with no BRCA1/2 mutation. Here, we assessed the contribution of SNPs of the iCOGS array in GENESIS consisting of BC cases with no BRCA1/2 mutation and a sister with BC, and population controls. Genotyping data were available for 1281 index cases, 731 sisters with BC, 457 unaffected sisters and 1272 controls. In addition to the standard SNP-level analysis using index cases and controls, we performed pedigree-based association tests to capture transmission information in the sibships. We also performed gene- and pathway-level analyses to maximize the power to detect associations with lower-frequency SNPs or those with modest effect sizes. While SNP-level analyses identified 18 loci, gene-level analyses identified 112 genes. Furthermore, 31 Kyoto Encyclopedia of Genes and Genomes and 7 Atlas of Cancer Signaling Network pathways were highlighted (false discovery rate of 5%). Using results from the "index case-control" analysis, we built pathway-derived polygenic risk scores (PRS) and assessed their performance in the population-based CECILE study and in a data set composed of GENESIS-affected sisters and CECILE controls. Although these PRS had poor predictive value in the general population, they performed better than a PRS built using our SNP-level findings, and we found that the joint effect of family history and PRS needs to be considered in risk prediction models.

5.
Occup Environ Med ; 2020 Oct 28.
Artigo em Inglês | MEDLINE | ID: mdl-33115922

RESUMO

OBJECTIVES: We evaluated the risk of lung cancer associated with ever working as a painter, duration of employment and type of painter by histological subtype as well as joint effects with smoking, within the SYNERGY project. METHODS: Data were pooled from 16 participating case-control studies conducted internationally. Detailed individual occupational and smoking histories were available for 19 369 lung cancer cases (684 ever employed as painters) and 23 674 age-matched and sex-matched controls (532 painters). Multivariable unconditional logistic regression models were adjusted for age, sex, centre, cigarette pack-years, time-since-smoking cessation and lifetime work in other jobs that entailed exposure to lung carcinogens. RESULTS: Ever having worked as a painter was associated with an increased risk of lung cancer in men (OR 1.30; 95% CI 1.13 to 1.50). The association was strongest for construction and repair painters and the risk was elevated for all histological subtypes, although more evident for small cell and squamous cell lung cancer than for adenocarcinoma and large cell carcinoma. There was evidence of interaction on the additive scale between smoking and employment as a painter (relative excess risk due to interaction >0). CONCLUSIONS: Our results by type/industry of painter may aid future identification of causative agents or exposure scenarios to develop evidence-based practices for reducing harmful exposures in painters.

6.
Environ Res ; 191: 110024, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-32777272

RESUMO

OBJECTIVES: Nanoscale particles (1-100 nm) can be of natural origin, and either intentionally or unintentionally produced by human activities. Toxicological data have suggested a possible carcinogenic effect of such particles. The aim of this study was to estimate the association between occupational exposure to nanoscale particles and risk of lung cancer, pleural mesothelioma and brain tumors in adults. METHODS: Three French population-based case-control studies were analyzed: 1) the ICARE study including 2029 lung cancer cases and 2591 controls; 2) the PNSM study including 371 pleural mesothelioma cases and 730 controls and 3) the CERENAT study including 257 brain tumor cases and 511 controls. Occupational exposure to unintentionally emitted nanoscale particles (UNPs) was retrospectively assessed by a job exposure matrix providing a probability and a frequency of exposure. RESULTS: In adjusted analyses among men, significant associations between occupational exposure to UNPs and lung cancer (OR = 1.51; 95% CI: 1.22-1.86 and brain tumors (OR = 1.69; 95% CI: 1.17-2.44) were observed. No increased OR was observed for pleural mesothelioma (OR = 0.78; 95% CI: 0.46-1.33). CONCLUSION: This is the first study showing positive associations between occupational exposure to UNPs and increased risk of lung cancer and brain tumors. These preliminary results should encourage further epidemiological research.

7.
PLoS One ; 15(8): e0236736, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32785269

RESUMO

Quantifying the association between lifetime exposures and the risk of developing a chronic disease is a recurrent challenge in epidemiology. Individual exposure trajectories are often heterogeneous and studying their associations with the risk of disease is not straightforward. We propose to use a latent class mixed model (LCMM) to identify profiles (latent classes) of exposure trajectories and estimate their association with the risk of disease. The methodology is applied to study the association between lifetime trajectories of smoking or occupational exposure to asbestos and the risk of lung cancer in males of the ICARE population-based case-control study. Asbestos exposure was assessed using a job exposure matrix. The classes of exposure trajectories were identified using two separate LCMM for smoking and asbestos, and the association between the identified classes and the risk of lung cancer was estimated in a second stage using weighted logistic regression and all subjects. A total of 2026/2610 cases/controls had complete information on both smoking and asbestos exposure, including 1938/1837 cases/controls ever smokers, and 1417/1520 cases/controls ever exposed to asbestos. The LCMM identified four latent classes of smoking trajectories which had different risks of lung cancer, all much stronger than never smokers. The most frequent class had moderate constant intensity over lifetime while the three others had either long-term, distant or recent high intensity. The latter had the strongest risk of lung cancer. We identified five classes of asbestos exposure trajectories which all had higher risk of lung cancer compared to men never occupationally exposed to asbestos, whatever the dose and the timing of exposure. The proposed approach opens new perspectives for the analyses of dose-time-response relationships between protracted exposures and the risk of developing a chronic disease, by providing a complete picture of exposure history in terms of intensity, duration, and timing of exposure.


Assuntos
Asbestos/efeitos adversos , Neoplasias Pulmonares/induzido quimicamente , Neoplasias Pulmonares/epidemiologia , Exposição Ocupacional/efeitos adversos , Fumar/efeitos adversos , Adulto , Idoso , Doença Crônica/epidemiologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Fatores de Risco
8.
Biopreserv Biobank ; 18(5): 376-388, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32608993

RESUMO

The integrity of blood plasma/serum (P/S) specimens can be impacted by preanalytical handling and storage conditions that result in thawed-state exposures (> -30°C). We recently reported a simple dilute-and-shoot, intact-protein liquid chromatography/mass spectrometry (LC/MS) assay called ΔS-Cys-Albumin that quantifies cumulative exposure of P/S to thawed conditions based on the change in relative abundance of the oxidized (S-cysteinylated) proteoform of albumin (S-Cys-Albumin) in the native sample to that of an aliquot of the sample intentionally driven to its maximum oxidation state. Herein, we evaluated the effect of prestorage delay and initial storage temperature on sample integrity by applying the ΔS-Cys-Albumin assay to a set of plasma samples (n = 413) collected under a single clinical study but from 12 different collection sites. Major differences (p < 0.0001) were observed between different groups of samples with modestly inconsistent initial handling conditions (i.e., initial processing of whole blood to plasma and placement at -80°C completed in under 3 hours, 3-13 hours, and over 17 hours). ΔS-Cys-Albumin was significantly inversely correlated with delay time at 4°C before centrifugation and total delay before final storage at -80°C (p < 0.0001). Samples from two collection sites had much lower ΔS-Cys-Albumin values relative to samples from other sites, in accordance with the fact that they were stored at -20°C for an average of 7.6 months before shipment to the central repository for final storage at -80°C. Based on the rate law for S-Cys-Albumin formation in plasma ex vivo, the average time that each plasma specimen had been exposed to the equivalent of room temperature (23°C) was back calculated from the measured ΔS-Cys-Albumin values. A survey of clinical analytes in P/S whose measured concentrations are sensitive to the initial handling/storage conditions documented in this study is provided and the ramifications of the plasma integrity findings from this multisite clinical study are discussed.

9.
Eur J Epidemiol ; 35(10): 937-948, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32681390

RESUMO

Rare cancers together constitute one fourth of cancers. As some rare cancers are caused by occupational exposures, a systematic search for further associations might contribute to future prevention. We undertook a European, multi-center case-control study of occupational risks for cancers of small intestine, bone sarcoma, uveal melanoma, mycosis fungoides, thymus, male biliary tract and breast. Incident cases aged 35-69 years and sex-and age-matched population/colon cancer controls were interviewed, including a complete list of jobs. Associations between occupational exposure and cancer were assessed with unconditional logistic regression controlled for sex, age, country, and known confounders, and reported as odds ratios (OR) with 95% confidence intervals (CI). Interviewed were 1053 cases, 2062 population, and 1084 colon cancer controls. Male biliary tract cancer was associated with exposure to oils with polychlorinated biphenyls; OR 2.8 (95% CI 1.3-5.9); male breast cancer with exposure to trichloroethylene; OR 1.9 (95% CI 1.1-3.3); bone sarcoma with job as a carpenter/joiner; OR 4.3 (95% CI 1.7-10.5); and uveal melanoma with job as a welder/sheet metal worker; OR 1.95 (95% CI 1.08-3.52); and cook; OR 2.4 (95% CI 1.4-4.3). A confirmatory study of printers enhanced suspicion of 1,2-dichloropropane as a risk for biliary tract cancer. Results contributed to evidence for classification of welding and 1,2-dichloropronane as human carcinogens. However, despite efforts across nine countries, for some cancer sites only about 100 cases were interviewed. The Rare Cancer Study illustrated both the strengths and limitations of explorative studies for identification of etiological leads.


Assuntos
Neoplasias/etiologia , Doenças Profissionais/etiologia , Exposição Ocupacional/efeitos adversos , Doenças Raras/etiologia , Adulto , Idoso , Estudos de Casos e Controles , Europa (Continente)/epidemiologia , Feminino , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Neoplasias/epidemiologia , Doenças Profissionais/epidemiologia , Doenças Raras/epidemiologia , Fatores de Risco
10.
Am J Respir Crit Care Med ; 202(3): 412-421, 2020 08 01.
Artigo em Inglês | MEDLINE | ID: mdl-32330394

RESUMO

Rationale: Millions of workers around the world are exposed to respirable crystalline silica. Although silica is a confirmed human lung carcinogen, little is known regarding the cancer risks associated with low levels of exposure and risks by cancer subtype. However, little is known regarding the disease risks associated with low levels of exposure and risks by cancer subtype.Objectives: We aimed to address current knowledge gaps in lung cancer risks associated with low levels of occupational silica exposure and the joint effects of smoking and silica exposure on lung cancer risks.Methods: Subjects from 14 case-control studies from Europe and Canada with detailed smoking and occupational histories were pooled. A quantitative job-exposure matrix was used to estimate silica exposure by occupation, time period, and geographical region. Logistic regression models were used to estimate exposure-disease associations and the joint effects of silica exposure and smoking on risk of lung cancer. Stratified analyses by smoking history and cancer subtypes were also performed.Measurements and Main Results: Our study included 16,901 cases and 20,965 control subjects. Lung cancer odds ratios ranged from 1.15 (95% confidence interval, 1.04-1.27) to 1.45 (95% confidence interval, 1.31-1.60) for groups with the lowest and highest cumulative exposure, respectively. Increasing cumulative silica exposure was associated (P trend < 0.01) with increasing lung cancer risks in nonsilicotics and in current, former, and never-smokers. Increasing exposure was also associated (P trend ≤ 0.01) with increasing risks of lung adenocarcinoma, squamous cell carcinoma, and small cell carcinoma. Supermultiplicative interaction of silica exposure and smoking was observed on overall lung cancer risks; superadditive effects were observed in risks of lung cancer and all three included subtypes.Conclusions: Silica exposure is associated with lung cancer at low exposure levels. An exposure-response relationship was robust and present regardless of smoking, silicosis status, and cancer subtype.


Assuntos
Adenocarcinoma de Pulmão/epidemiologia , Carcinoma de Células Pequenas/epidemiologia , Carcinoma de Células Escamosas/epidemiologia , Neoplasias Pulmonares/epidemiologia , Exposição Ocupacional/estatística & dados numéricos , Dióxido de Silício , Silicose/epidemiologia , Adulto , Idoso , Canadá/epidemiologia , Fumar Cigarros , Europa (Continente)/epidemiologia , Feminino , Humanos , Exposição por Inalação , Neoplasias Pulmonares/patologia , Masculino , Pessoa de Meia-Idade
11.
Am J Respir Crit Care Med ; 202(3): 402-411, 2020 08 01.
Artigo em Inglês | MEDLINE | ID: mdl-32330395

RESUMO

Rationale: Although the carcinogenicity of diesel engine exhaust has been demonstrated in multiple studies, little is known regarding exposure-response relationships associated with different exposure subgroups and different lung cancer subtypes.Objectives: We expanded on a previous pooled case-control analysis on diesel engine exhaust and lung cancer by including three additional studies and quantitative exposure assessment to evaluate lung cancer and subtype risks associated with occupational exposure to diesel exhaust characterized by elemental carbon (EC) concentrations.Methods: We used a quantitative EC job-exposure matrix for exposure assessment. Unconditional logistic regression models were used to calculate lung cancer odds ratios and 95% confidence intervals (CIs) associated with various metrics of EC exposure. Lung cancer excess lifetime risks (ELR) were calculated using life tables accounting for all-cause mortality. Additional stratified analyses by smoking history and lung cancer subtypes were performed in men.Measurements and Main Results: Our study included 16,901 lung cancer cases and 20,965 control subjects. In men, exposure response between EC and lung cancer was observed: odds ratios ranged from 1.09 (95% CI, 1.00-1.18) to 1.41 (95% CI, 1.30-1.52) for the lowest and highest cumulative exposure groups, respectively. EC-exposed men had elevated risks in all lung cancer subtypes investigated; associations were strongest for squamous and small cell carcinomas and weaker for adenocarcinoma. EC lung cancer exposure response was observed in men regardless of smoking history, including in never-smokers. ELR associated with 45 years of EC exposure at 50, 20, and 1 µg/m3 were 3.0%, 0.99%, and 0.04%, respectively, for both sexes combined.Conclusions: We observed a consistent exposure-response relationship between EC exposure and lung cancer in men. Reduction of workplace EC levels to background environmental levels will further reduce lung cancer ELR in exposed workers.


Assuntos
Adenocarcinoma de Pulmão/epidemiologia , Carcinoma de Células Grandes/epidemiologia , Carcinoma de Células Pequenas/epidemiologia , Carcinoma de Células Escamosas/epidemiologia , Fumar Cigarros/epidemiologia , Neoplasias Pulmonares/epidemiologia , Exposição Ocupacional/estatística & dados numéricos , Emissões de Veículos , Adulto , Idoso , Canadá/epidemiologia , Carbono , Europa (Continente)/epidemiologia , Feminino , Humanos , Exposição por Inalação , Masculino , Pessoa de Meia-Idade , Razão de Chances , Fatores Sexuais
12.
PLoS One ; 15(1): e0228187, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-31999731

RESUMO

BACKGROUND: GSTM1 and GSTT1 are involved in detoxification of xenobiotics, products of oxidative stress and in steroid hormones metabolism. We investigated whether GSTM1 and GSTT1 gene deletion was associated with DTC risk and explored interaction with non-genetic risk factors of DTC. METHODS: The study included 661 DTC cases and 736 controls from two case-control studies conducted in France and New Caledonia. Odds ratios (OR) and their confidence interval (CI) for DTC associated with GST genotypes, alcohol drinking, tobacco smoking, body mass index and hormonal factors were calculated using logistic regression models. RESULTS: Results are presented for Europeans and Melanesians combined, as no heterogeneity between groups was detected. We found that DTC risk increased with obesity and decrease with alcohol drinking. After stratification by gene deletion status, the OR for obesity was 5.75, (95%CI 2.25-14.7) among individuals with GSTT1 and GSTM1-deleted genotype, and 1.26, (95%CI 0.89-1.77) in carriers of both genes (p-interaction = 0.02). The OR for drinking ≥1 glass/week was 0.33 (95%CI 0.15-0.74) in GSTT1-null individuals while it was 1.01 (95%CI 0.67-1.52) in non-null carriers of the gene (p-interaction = 0.01). No interaction between GST genotypes and other non-genetic risk factors was detected. CONCLUSION: GSTM1 and GSTT1 genotypes may modulate the DTC risk associated with BMI and alcohol consumption.


Assuntos
Glutationa Transferase/genética , Estilo de Vida , Neoplasias da Glândula Tireoide/genética , Consumo de Bebidas Alcoólicas/efeitos adversos , Índice de Massa Corporal , Estudos de Casos e Controles , Feminino , Deleção de Genes , Genótipo , Hormônios Esteroides Gonadais/metabolismo , Comportamentos de Risco à Saúde , Humanos , Masculino , Pessoa de Meia-Idade , Nova Caledônia , Obesidade/complicações , Neoplasias da Glândula Tireoide/etiologia
13.
Am J Epidemiol ; 189(2): 95-107, 2020 02 28.
Artigo em Inglês | MEDLINE | ID: mdl-31509174

RESUMO

Despite research efforts, current knowledge of the etiology of thyroid carcinoma remains limited. To explore the potential role of diet-induced inflammation, we examined the association between differentiated thyroid cancer risk and the energy-adjusted Dietary Inflammatory Index (E-DII) in a population-based case-control study conducted in New Caledonia, a Pacific archipelago with one of the highest recorded thyroid cancer incidence rates in the world. The E-DII was computed from food frequency questionnaire information on usual dietary intake. Logistic regression analyses were performed on data from 324 histologically confirmed cases of papillary or follicular carcinoma, diagnosed from 1993 to 1999, and 402 controls. Positive associations between E-DII and thyroid cancer risk were observed (comparing extreme tertiles, odds ratio = 1.67, 95% confidence interval: 1.08, 2.58; P for trend = 0.002), with stronger associations found for larger carcinomas (P for trend = 0.0005). Stratified analyses showed an increased risk of thyroid cancer associated with the E-DII among Southern province residents (P for trend = 0.003), Melanesian women (P for trend = 0.02), obese participants (P for trend = 0.006), and ever-smokers (P for trend = 0.0005). Our results suggest that a proinflammatory diet-especially when concomitant with other inflammation-inducing conditions or habits (e.g., obesity, smoking)-is associated with increased risk of thyroid carcinoma.


Assuntos
Carcinoma/epidemiologia , Dieta Saudável/estatística & dados numéricos , Dieta/efeitos adversos , Inflamação/epidemiologia , Neoplasias da Glândula Tireoide/epidemiologia , Adulto , Idoso , Carcinoma/etiologia , Estudos de Casos e Controles , Inquéritos sobre Dietas , Feminino , Humanos , Inflamação/etiologia , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Nova Caledônia/epidemiologia , Razão de Chances , Fatores de Risco , Neoplasias da Glândula Tireoide/etiologia
14.
J Proteome Res ; 18(11): 3985-3998, 2019 11 01.
Artigo em Inglês | MEDLINE | ID: mdl-31566983

RESUMO

Lung cancer is the leading cause of cancer death in women living in the United States, which accounts for approximately the same percentage of cancer deaths in women as breast, ovary, and uterine cancers combined. Targeted blood plasma glycomics represents a promising source of noninvasive diagnostic and prognostic biomarkers for lung cancer. Here, 208 samples from lung cancer patients and 207 age-matched controls enrolled in the Women Epidemiology Lung Cancer (WELCA) study were analyzed by a bottom-up glycan "node" analysis approach. Glycan features, quantified as single analytical signals, including 2-linked mannose, α2-6 sialylation, ß1-4 branching, ß1-6 branching, 4-linked GlcNAc, and antennary fucosylation, exhibited abilities to distinguish cases from controls (ROC AUCs: 0.68-0.92) and predict survival in patients (hazard ratios: 1.99-2.75) at all stages. Notable alterations of glycan features were observed in stages I-II. Diagnostic and prognostic glycan features were mostly independent of smoking status, age, gender, and histological subtypes of lung cancer.


Assuntos
Biomarcadores Tumorais/metabolismo , Glicômica/métodos , Neoplasias Pulmonares/metabolismo , Polissacarídeos/metabolismo , Idoso , Biomarcadores Tumorais/sangue , Estudos de Casos e Controles , Feminino , Glicosilação , Humanos , Neoplasias Pulmonares/diagnóstico , Neoplasias Pulmonares/epidemiologia , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Polissacarídeos/sangue , Prognóstico , Curva ROC , Análise de Sobrevida
15.
Cancer Epidemiol ; 61: 133-138, 2019 08.
Artigo em Inglês | MEDLINE | ID: mdl-31254794

RESUMO

PURPOSE: Hardly anything is known about the aetiology of thymoma. This paper presents data regarding tobacco smoking and alcohol consumption in relation to thymoma from the first case-control study performed on this rare tumour. METHODS: A European multi-centre case-control study including incident cases aged 35-69 years with thymoma between 1995 and 1997, was conducted in seven countries. A set of controls, used in seven parallel case-control studies by the same research group was used, including population-based controls from five countries and hospital controls with colon cancer from two countries. Altogether 103 cases, accepted by a reference pathologist, 712 colon cancer controls, and 2071 population controls were interviewed. RESULTS: Tobacco smoking was moderately related with thymoma (OR 1.4, 95% CI 0.9-2.2), and a tendency to dose-response was shown (p = 0.04), with an increased risk for heavy smokers defined as ≥41 pack-years (OR 2.1, 95% CI 1.1-3.9). A high consumption of spirits defined as ≥25 g of alcohol per day was associated with an increased risk of thymoma (OR 2.4, 95% CI 1.1-5.4), whereas no association was found with beer or wine. CONCLUSIONS: Tobacco smoking and a high intake of spirits were indicated as risk factors for thymoma.


Assuntos
Consumo de Bebidas Alcoólicas/efeitos adversos , Timoma/etiologia , Fumar Tabaco/efeitos adversos , Adulto , Idoso , Estudos de Casos e Controles , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Fatores de Risco
17.
Artigo em Inglês | MEDLINE | ID: mdl-30669331

RESUMO

Exposure to environmental chemicals with hormonal effects, such as organochlorine compounds (OCs), during developmental periods of breast cells may have an impact on the incidence of breast cancer later in life. However, the assessment of exposure to these chemicals that occurred in early life at the time of breast cancer development in adult women is a difficult challenge in epidemiological studies. Plasma levels of the OCs p,p'-dichlorodiphenyl dichloroethene (DDE) and polychlorinated biphenyl congener 153 (PCB153) were measured in 695 cases and 1055 controls of a population-based case-control study conducted in France (CECILE study). Based on these values, we used a physiologically-based pharmacokinetic (PBPK) model to estimate PCB153 levels at age 11⁻20 years when the women were adolescents. Overall, there was no clear association between breast cancer risk and measured levels of DDE and PCB153 at the time of diagnosis, but there was a trend of decreasing odds ratios of breast cancer with increasing DDE and PCB153 levels in women aged 50 years and over. The PBPK model revealed that PCB153 concentrations estimated during adolescence were highest in the youngest women born after 1960 who reached adolescence at a time when environmental contamination was maximum, and very low in the oldest women who attained adolescence before the contamination peak. Negative associations between breast cancer and PCB153 estimates during adolescence were also found. The negative associations between DDE and PCB153 levels measured at the time of diagnosis or estimated during adolescence in our study were unexplained. Further investigations are needed to clarify whether this finding is real or related to study artifacts. However, this study suggests that using PBPK models in epidemiological studies to back-estimate OC exposures during early life stages may be useful to address critical questions on cancer development.


Assuntos
Neoplasias da Mama/sangue , Disruptores Endócrinos/sangue , Poluentes Ambientais/sangue , Hidrocarbonetos Clorados/sangue , Neoplasias da Mama/diagnóstico , Neoplasias da Mama/epidemiologia , Estudos de Casos e Controles , Feminino , França/epidemiologia , Avaliação do Impacto na Saúde , Humanos , Pessoa de Meia-Idade , Modelos Biológicos , Razão de Chances , Farmacocinética , Vigilância da População
18.
Int J Hyg Environ Health ; 222(1): 22-29, 2019 01.
Artigo em Inglês | MEDLINE | ID: mdl-30174219

RESUMO

BACKGROUND: Recent and comprehensive estimates for the number of new cancer cases in France attributable to occupational exposures are lacking. OBJECTIVES: To estimate the number of new cancer cases attributable to occupational exposures, using a newly developed methodology and the most recent data, for a comprehensive set of occupational carcinogens in France in 2015. METHODS: Surveys among employees, the national labor force data, a cohort of agricultural workers, national monitoring of workers exposed to ionizing radiation and job-exposure matrix in France were used. The number and proportion of new cancer cases attributable to established occupational carcinogens (Group 1) was estimated using estimation of lifetime exposure and risk estimates from cohort studies. Cancer data were obtained from the French Cancer Registries Network. RESULTS: In France in 2015, an estimated 7905 new cancer cases, 7336 among men and 569 among women, were attributable to occupational exposures, representing 2.3% of all new cancer cases (3.9% and 0.4% among men and women respectively). Among men and women, lung cancer was impacted the most, followed by mesothelioma and bladder cancer in men, and by mesothelioma and ovary in women. These cancers contributed to 89% of the total cancers attributable to occupational carcinogens in men, and to 80% in women. The main contributing occupational agent was asbestos among men (45%) and women (60%). CONCLUSIONS: Currently, occupational exposures contribute to a substantial burden of cancer in France. Enhanced monitoring and implementation of protective labor policies could potentially prevent a large proportion of these cancers.


Assuntos
Carcinógenos/toxicidade , Neoplasias/induzido quimicamente , Exposição Ocupacional/efeitos adversos , Feminino , França/epidemiologia , Humanos , Masculino , Neoplasias/epidemiologia , Exposição Ocupacional/estatística & dados numéricos
19.
Int J Cancer ; 144(8): 1896-1908, 2019 04 15.
Artigo em Inglês | MEDLINE | ID: mdl-30303517

RESUMO

Single nucleotide polymorphisms (SNPs) in genes involved in xenobiotics metabolism (XM) are suspected to play a role in breast cancer risk. However, previous findings based on a SNP by SNP approach need to be replicated taking into account the combined effects of multiple SNPs. We used a gene-set analysis method to study the association between breast cancer risk and genetic variation in XM genes (seen as a set of SNPs) and in the XM pathway (seen as a set of genes). We also studied the interaction between variants in XM genes and tobacco smoking. The analysis was conducted in a case-control study of 1,125 cases and 1,172 controls. Using a dedicated chip, genotyping data of 585 SNPs in 68 XM genes were available. Genetic variation in the whole XM pathway was significantly associated with premenopausal breast cancer risk (p = 0.008). This association was mainly driven by genetic variation in NAT2, CYP2C18, CYP2C19, AKR1C2 and ALDH1A3. The association between the XM gene pathway and breast cancer was observed among current and previous smokers, but not among never smokers (p = 0.013 for interaction between XM genes and tobacco smoking status). The association with breast cancer risk indicates that XM genes variants may play a role in breast carcinogenesis through their detoxification function of environmental pollutants, such as those contained in tobacco smoke.


Assuntos
Neoplasias da Mama/genética , Predisposição Genética para Doença , Redes e Vias Metabólicas/genética , Fumar Tabaco/efeitos adversos , Xenobióticos/metabolismo , Adulto , Idoso , Neoplasias da Mama/epidemiologia , Neoplasias da Mama/etiologia , Carcinogênese/genética , Estudos de Casos e Controles , Feminino , Genótipo , Humanos , Incidência , Pessoa de Meia-Idade , Polimorfismo de Nucleotídeo Único , Fatores de Risco , Fumaça/efeitos adversos , Tabaco/efeitos adversos , Fumar Tabaco/epidemiologia
20.
Occup Environ Med ; 75(8): 586-592, 2018 08.
Artigo em Inglês | MEDLINE | ID: mdl-29777039

RESUMO

OBJECTIVE: To estimate the impact of intensity of both smoking and occupational exposure to asbestos on the risk of lung cancer throughout the whole exposure history. METHODS: Data on 2026 male cases and 2610 male controls came from the French ICARE (Investigation of occupational and environmental causes of respiratory cancers) population-based, case-control study. Lifetime smoking history and occupational history were collected from standardised questionnaires and face-to-face interviews. Occupational exposure to asbestos was assessed using a job exposure matrix. The effects of annual average daily intensity of smoking (reported average number of cigarettes smoked per day) and asbestos exposure (estimated average daily air concentration of asbestos fibres at work) were estimated using a flexible weighted cumulative index of exposure in logistic regression models. RESULTS: Intensity of smoking in the 10 years preceding diagnosis had a much stronger association with the risk of lung cancer than more distant intensity. By contrast, intensity of asbestos exposure that occurred more than 40 years before diagnosis had a stronger association with the risk of lung cancer than more recent intensity, even if intensity in the 10 years preceding diagnosis also had a significant effect. CONCLUSION: Our results illustrate the dynamic of the effect of intensity of both smoking and occupational exposure to asbestos on the risk of lung cancer. They confirm that the timing of exposure plays an important role, and suggest that standard analytical methods assuming equal weights of intensity over the whole exposure history may be questionable.


Assuntos
Neoplasias Pulmonares/etiologia , Doenças Profissionais/etiologia , Exposição Ocupacional/efeitos adversos , Fumar/efeitos adversos , Adolescente , Adulto , Idoso , Asbestos , Estudos de Casos e Controles , Feminino , Humanos , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Razão de Chances , Neoplasias do Sistema Respiratório , Fatores de Risco , Adulto Jovem
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