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1.
  • Behrens, Thomas, et al. (författare)
  • Hormonal exposures and the risk of uveal melanoma
  • 2010
  • Ingår i: Cancer Causes and Control. - : Springer Science and Business Media LLC. - 1573-7225 .- 0957-5243. ; 21:10, s. 1625-1634
  • Tidskriftsartikel (refereegranskat)abstract
    • Several studies suggest that hormonal mechanisms may be associated with the development of uveal melanoma. Therefore, the association between the risk of uveal melanoma and exposure to hormonal exposures was investigated in a case-control study from nine European countries. Incident cases of uveal melanoma were frequency-matched to population and hospital controls by country, age, and sex. Female subjects were asked about their reproductive history, use of menopausal hormone replacement therapy and oral contraceptives. Among men, occupational handling of oils while working with transformers or capacitors which contain polychlorinated biphenyls (PCB) was solicited. Unconditional logistic regression analyses were calculated, adjusting for several potential confounders. Analyses were stratified by sex. Two hundred and ninety-three cases (165 men, 128 women) and 3,198 control subjects (2,121 men, 1,077 women) were interviewed. Among women, no associations were observed with hormonal status variables, intake of hormonal therapy or intake of oral contraceptives. Men showed an increased risk with occupational exposure to transformer/capacitor oils (OR = 2.74; Bonferroni-corrected 99.3% CI 1.07-7.02). However, these results were based on few exposed subjects only. The results of this study do not support the hypothesis of a hormonal influence in the carcinogenesis of uveal melanoma. Our finding of a potentially increased risk with PCB-containing oils requires further research.
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2.
  • Guénel, Pascal, et al. (författare)
  • Alcohol drinking may increase risk of breast cancer in men : a European population-based case-control study
  • 2004
  • Ingår i: Cancer Causes and Control. - 1573-7225 .- 0957-5243. ; 15:6, s. 80-571
  • Tidskriftsartikel (refereegranskat)abstract
    • OBJECTIVE: It has been estimated that alcohol drinking increases the risk of breast cancer in women by approximately 7% for each increment of 10 g alcohol per day. However, the few studies conducted on breast cancer among men have failed to detect an association with quantitative measures of alcohol drinking, even if the alcohol intake is generally higher in men than in women. On the other hand, increased risks of male breast cancer were inconsistently reported in alcoholics or patients with liver cirrhosis. We have investigated the role of alcohol drinking in male breast cancer using data collected in a population-based case-control study on seven rare cancers, conducted in Denmark, France, Germany, Italy, and Sweden.METHODS: The cases were 74 histologically verified male breast cancer patients aged 35-70 years. The controls (n = 1432) were selected from population registers, and frequency-matched to the cases by age group and geographic area. To check for consistency, a separate analysis was conducted using as controls the patients with a rare cancer other than male breast recruited simultaneously in the European study (n = 519 men).RESULTS: Based on population controls, the risk of developing breast cancer in men increased by 16% (95% CI: 7-26%) per 10 g alcohol /day (p < 0.001). An odds ratio of 5.89 (95% CI: 2.21-15.69) was observed for alcohol intake greater than 90 g per day, as compared with light consumers (< 15 g per day). Similar associations were observed when other rare cancers patients were used as controls.CONCLUSION: We found that the relative risk of breast cancer in men is comparable to that in women for alcohol intakes below 60 g per day. It continues to increase at high consumption levels not usually studied in women.
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3.
  • Holmila, Reetta, et al. (författare)
  • COX-2 and p53 in human sinonasal cancer: COX-2 expression is associated with adenocarcinoma histology and wood-dust exposure
  • 2008
  • Ingår i: International Journal of Cancer. - : Wiley. - 0020-7136. ; 122:9, s. 2154-2159
  • Tidskriftsartikel (refereegranskat)abstract
    • The causal role of wood-dust exposure in sinonasal cancer (SNC) has been established in epidemiological studies, but the mechanisms of SNC carcinogenesis are still largely unknown. Increased amounts of COX-2 are found in both premalignant and malignant tissues, and experimental evidence link COX-2 to development of cancer. Many signals that activate COX-2 also induce tumor suppressor p53, a transcription factor central in cellular stress response. We investigated COX-2 and p53 expressions by immunohistochemistry in 50 SNCs (23 adenocarcinomas, and 27 squamous cell carcinomas (SCC); 48 analyzed for COX-2; 41 for p53). Occupational histories and smoking habits were available for majority of the cases. Most of the adenocarcinoma cases with exposure history data had been exposed to wood dust at work in the past (88%, 14/16). For smokers, 63% (12/19) presented with SSC, whereas 64% (7/11) of nonsmokers displayed adenocarcinoma. COX-2 was expressed at higher levels in adenocarcinoma as compared to SSC (p < 0.001). COX-2 expression showed significant association with occupational exposure to wood dust (p = 0.024), and with nonsmoking status (p = 0.001). No statistically significant associations between the exposures and p53 accumulation were found; however, the p53 accumulation pattern (p = 0.062 for wood dust exposure) resembled that of COX-2 expression. In summary, our findings show increased COX-2 expression in SNC adenocarcinoma with wood dust exposure, suggesting a role for inflammatory components in the carcinogenesis process. In contrast, SCCs predominated among smokers and expressed COX-2 rarely; this may suggest at least partially different molecular mechanisms.
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4.
  • Holmila, Reetta, et al. (författare)
  • Mutations in TP53 tumor suppressor gene in wood dust-related sinonasal cancer
  • 2010
  • Ingår i: International Journal of Cancer. - : Wiley. - 0020-7136 .- 1097-0215. ; 127:3, s. 578-588
  • Tidskriftsartikel (refereegranskat)abstract
    • The causal role of work-related exposure to wood dust in the development of sinonasal cancer has long been established by numerous epidemiologic studies. To study molecular changes in these tumors, we analyzed TP53 gene mutations in 358 sinonasal cancer cases with or without occupational exposure to wood dust, using capillary electrophoresis single-strand conformation polymorphism analysis and direct sequencing. A significant association between wood-dust exposure and adenocarcinoma histology was observed [adjusted odds ratio (OR) 12.6, 95% confidence interval (Cl), 5.0-31.6]. TP53 mutations occurred in all histologies, with an overall frequency of 77%. TP53 mutation positive status was most common in adenocarcinoma (OR 2.0, 95% Cl, 1.1-3.7; compared with squamous cell carcinoma), and mutation positivity showed an overall, nonsignificant association with wood-dust exposure (OR 1.6, 95% Cl, 0.8-3.1). Risk of TP53 mutation was significantly increased in association with duration (>= 24 years, OR 5.1, 95% Cl, 1.5-17.1), average level (>2 mg/m(3); OR 3.6, 95% Cl, 1.2-10.8) and cumulative level (>= 30 mg/m(3) x years; OR 3.5, 95% Cl, 1.2-10.7) of wood-dust exposure; adjustment for formaldehyde affected the ORs only slightly. Smoking did not influence the occurrence of TP53 mutation; however, it was associated with multiple mutations (p = 0.03). As far as we are aware, this is the first study to demonstrate a high prevalence of TP53 mutation-positive cases in a large collection of sinonasal cancers with data on occupational exposure. Our results indicate that mutational mechanisms, in particular TP53 mutations, are associated with work-related exposure to wood dust in sinonasal cancer.
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5.
  • Holmila, Reetta, et al. (författare)
  • Profile of TP53 gene mutations in sinonasal cancer
  • 2010
  • Ingår i: Mutation Research - Fundamental and Molecular Mechanisms of Mutagenesis. - : Elsevier BV. - 1879-2871 .- 0027-5107. ; 686:1-2, s. 9-14
  • Tidskriftsartikel (refereegranskat)abstract
    • Genetic alterations underlying the development of the cancer of the nose and paranasal sinuses (sinonasal cancer, SNC), a rare cancer that can be included in the group of head and neck cancers, are still largely unknown. We recently reported that TP53 mutations are a common feature of SNC, with an overall frequency of 77%, and they show association to adenocarcinoma and wood-dust exposure [15]. In this study, we report in detail the sequence change for 159 TP53 mutations identified by direct sequencing. More than half of the mutations (60%, 95/159) were missense mutations; there were also 28(18%) frameshift or nonsense mutations, and 36 (23%) intronic or silent mutations. In coding region, the most common base change detected was C --> T transition (43/125; 34% of base changes in the coding region). G --> T transversions occurred at a frequency of 10% (12/125), which is less than reported in mutation databases for head and neck squamous cell carcinoma (24%). Characteristically, in our SNC series, the mutations were scattered over a large number of codons, codon 248 being the most frequent target of base substitution. Codon 135 was the second most frequently mutated codon; this nucleotide position has not been reported before as frequently mutated in head and neck cancer or human cancer in general. About half of all tumours with TP53 mutations carried more than one mutation. Interestingly, 86% (19/22) of the silent mutations detected had occurred in tumours with multiple mutations. (C) 2009 Elsevier B.V. All rights reserved.
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6.
  • Morales-Suarez-Varela, Maria M., et al. (författare)
  • Occupational Exposure to Chlorinated and Petroleum Solvents and Mycosis Fungoides
  • 2013
  • Ingår i: Journal of Occupational and Environmental Medicine. - : Lippincott Williams & Wilkins. - 1076-2752 .- 1536-5948. ; 55:8, s. 924-931
  • Tidskriftsartikel (refereegranskat)abstract
    • Objective: To evaluate the potential association between occupational exposure to chlorinated and petroleum solvents and mycosis fungoides (MF). Methods: A questionnaire on lifetime job history was administered to 100 patients diagnosed with MF and 2846 controls. Odds ratios (ORs) were calculated as the measure of the association between exposure to each specific solvent and MF. Results: In the total sample and in men, cases and controls did not differ in relation to exposure to any of the solvents studied. In women, an association with MF was seen for the highest level of estimated exposure to perchloroethylene (OR = 11.38; 95% confidence interval: 1.04 to 124.85) and for exposure less than the median to kerosene/fuel/gasoil (OR = 8.53; 95% confidence interval: 1.11 to 65.62). Conclusions: These results do not provide conclusive evidence that exposure to solvents may increase risk of MF because they were not found in men.
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7.
  • Villeneuve, Sara, et al. (författare)
  • Occupation and occupational exposure to endocrine disrupting chemicals in male breast cancer: a case-control study in Europe
  • 2010
  • Ingår i: Occupational and Environmental Medicine. - : BMJ. - 1470-7926 .- 1351-0711. ; 67:12, s. 837-844
  • Tidskriftsartikel (refereegranskat)abstract
    • Objectives Male breast cancer is a rare disease of largely unknown aetiology. In addition to genetic and hormone-related risk factors, a large number of environmental chemicals are suspected of playing a role in breast cancer. The identification of occupations or occupational exposures associated with an increased incidence of breast cancer in men may help to identify mammary carcinogens in the environment. Methods Occupational risk factors for male breast cancer were investigated in a multi-centre case-control study conducted in eight European countries which included 104 cases and 1901 controls. Lifetime work history was obtained during in-person interviews. Occupational exposures to endocrine disrupting chemicals (alkylphenolic compounds, phthalates, polychlorinated biphenyls and dioxins) were assessed on a case-by-case basis using expert judgement. Results Male breast cancer incidence was particularly increased in motor vehicle mechanics (OR 2.1, 95% CI 1.0 to 4.4) with a dose-effect relationship with duration of employment. It was also increased in paper makers and painters, forestry and logging workers, health and social workers, and furniture manufacture workers. The OR for exposure to alkylphenolic compounds above the median was 3.8 (95% CI 1.5 to 9.5). This association persisted after adjustment for occupational exposures to other environmental oestrogens. Conclusion These findings suggest that some environmental chemicals are possible mammary carcinogens. Petrol, organic petroleum solvents or polycyclic aromatic hydrocarbons are suspect because of the consistent elevated risk of male breast cancer observed in motor vehicle mechanics. Endocrine disruptors such as alkylphenolic compounds may play a role in breast cancer.
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8.
  • 2019
  • Tidskriftsartikel (refereegranskat)
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