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Sökning: WFRF:(Guénel Pascal)

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1.
  • Lawrenson, Kate, et al. (författare)
  • Functional mechanisms underlying pleiotropic risk alleles at the 19p13.1 breast-ovarian cancer susceptibility locus
  • 2016
  • Ingår i: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 7
  • Tidskriftsartikel (refereegranskat)abstract
    • A locus at 19p13 is associated with breast cancer (BC) and ovarian cancer (OC) risk. Here we analyse 438 SNPs in this region in 46,451 BC and 15,438 OC cases, 15,252 BRCA1 mutation carriers and 73,444 controls and identify 13 candidate causal SNPs associated with serous OC (P=9.2 × 10-20), ER-negative BC (P=1.1 × 10-13), BRCA1-associated BC (P=7.7 × 10-16) and triple negative BC (P-diff=2 × 10-5). Genotype-gene expression associations are identified for candidate target genes ANKLE1 (P=2 × 10-3) and ABHD8 (P<2 × 10-3). Chromosome conformation capture identifies interactions between four candidate SNPs and ABHD8, and luciferase assays indicate six risk alleles increased transactivation of the ADHD8 promoter. Targeted deletion of a region containing risk SNP rs56069439 in a putative enhancer induces ANKLE1 downregulation; and mRNA stability assays indicate functional effects for an ANKLE1 3′-UTR SNP. Altogether, these data suggest that multiple SNPs at 19p13 regulate ABHD8 and perhaps ANKLE1 expression, and indicate common mechanisms underlying breast and ovarian cancer risk.
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2.
  • Ahearn, Thomas U., et al. (författare)
  • Common variants in breast cancer risk loci predispose to distinct tumor subtypes
  • 2022
  • Ingår i: Breast Cancer Research. - : Springer Nature. - 1465-5411 .- 1465-542X. ; 24:1
  • Tidskriftsartikel (refereegranskat)abstract
    • BackgroundGenome-wide association studies (GWAS) have identified multiple common breast cancer susceptibility variants. Many of these variants have differential associations by estrogen receptor (ER) status, but how these variants relate with other tumor features and intrinsic molecular subtypes is unclear.MethodsAmong 106,571 invasive breast cancer cases and 95,762 controls of European ancestry with data on 173 breast cancer variants identified in previous GWAS, we used novel two-stage polytomous logistic regression models to evaluate variants in relation to multiple tumor features (ER, progesterone receptor (PR), human epidermal growth factor receptor 2 (HER2) and grade) adjusting for each other, and to intrinsic-like subtypes.ResultsEighty-five of 173 variants were associated with at least one tumor feature (false discovery rate < 5%), most commonly ER and grade, followed by PR and HER2. Models for intrinsic-like subtypes found nearly all of these variants (83 of 85) associated at p < 0.05 with risk for at least one luminal-like subtype, and approximately half (41 of 85) of the variants were associated with risk of at least one non-luminal subtype, including 32 variants associated with triple-negative (TN) disease. Ten variants were associated with risk of all subtypes in different magnitude. Five variants were associated with risk of luminal A-like and TN subtypes in opposite directions.ConclusionThis report demonstrates a high level of complexity in the etiology heterogeneity of breast cancer susceptibility variants and can inform investigations of subtype-specific risk prediction.
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3.
  • Ahrens, Wolfgang, et al. (författare)
  • Occupational exposure to endocrine-disrupting compounds and biliary tract cancer among men
  • 2007
  • Ingår i: Scandinavian Journal of Work, Environment and Health. - : Scandinavian Journal of Work, Environment and Health. - 0355-3140 .- 1795-990X. ; 33:5, s. 387-396
  • Tidskriftsartikel (refereegranskat)abstract
    • Objectives This study investigated the association between cancer of the extrahepatic biliary tract and exposure to endocrine-disrupting compounds. Methods Altogether 183 men with histologically confirmed carcinoma of the extrahepatic biliary tract and 1938 matched controls were interviewed between 1995 and 1997 in the frame of an international multicenter case-control study in six European countries (Denmark, France, Germany, Italy, Spain, and Sweden). Selfreported job descriptions were converted to semiquantitative variables (intensity, probability, and duration of exposure) for 14 endocrine-disrupting compounds. The cases were compared with 1421 population controls and 517 colon adenocarcinoma patients. Odds ratios (OR) and 95% confidence intervals (95% CI) were obtained with unconditional logistic regression and adjusted for age, country, and gallstones. Results Occupational exposure to endocrine-disrupting compounds resulted in an OR of 1.4 (95% CI 1.0-2. 1) with no dose-effect relationship for cumulative exposure (low: OR 1.3, 95% CI 0.6-3.0; medium: OR 1.5, 95% CI0.8-2.7; high: OR 1.4, 95% CI 0.9-2.4) (only index participants). The elevated risk was restricted to extrahepatic bile ducts and ampulla Vateri (OR 1.7, 95% CI 1.0-2.6). The adjusted OR for cancer of the extrahepatic biliary tract after exposure to polychlorinated biphenyls was 2.8 (95% CI 1.3-5.9, only index participants). Conclusions The data show some associations between exposure to endocrine-disrupting compounds in the workplace and the risk for cancer of the extrahepatic biliary tract among men, particularly for the extrahepatic bile duct and ampulla of Vater. Polychlorinated biphenyls could possibly be a strong risk factor.
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4.
  • Ahrens, Wolfgang, et al. (författare)
  • Risk factors for extrahepatic biliary tract carcinoma in men: medical conditions and lifestyle: results from a European multicentre case-control study
  • 2007
  • Ingår i: European Journal of Gastroenterology and Hepathology. - 1473-5687. ; 19:8, s. 623-630
  • Tidskriftsartikel (refereegranskat)abstract
    • OBJECTIVES: To identify risk factors of carcinoma of the extrahepatic biliary tract in men. METHODS: Newly diagnosed and histologically confirmed patients, 35-70 years old, were interviewed between 1995 and 1997 in Denmark, Sweden, France, Germany and Italy. Population controls were frequency-matched by age and region. Adjusted odds ratios and 95%-confidence intervals were estimated by logistic regression. RESULTS: The analysis included 153 patients and 1421 controls. The participation proportion was 71% for patients and 61% for controls. Gallstone disease was corroborated as a risk factor for extrahepatic biliary tract carcinoma in men (odds ratio 2.49; 95% confidence interval 1.32-4.70), particularly for gall bladder tumors (odds ratio 4.68; 95% confidence interval 1.85-11.84). For a body mass index [height (m) divided by squared weight (kg2)] >30 at age 35 years, an excess risk was observed (odds ratio 2.58; 95% confidence interval 1.07-6.23, reference: body mass index 18.5-25) that was even stronger if the body mass index was >30 for the lowest weight in adulthood (odds ratio 4.68; 95% confidence interval 1.13-19.40). Infection of the gall bladder, chronic inflammatory bowel disease, hepatitis or smoking showed no clear association, whereas some increase in risk was suggested for consumption of 40-80 g alcohol per day and more. CONCLUSIONS: Our study corroborates gallstones as a risk indicator in extrahepatic biliary tract carcinoma. Permanent overweight and obesity in adult life was identified as a strong risk factor for extrahepatic biliary tract carcinoma, whereas we did not find any strong lifestyle-associated risk factors. Inconsistent results across studies concerning the association of extrahepatic biliary tract carcinoma with overweight and obesity may be explained by the different approaches to assess this variable.
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5.
  • 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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6.
  • Behrens, Thomas, et al. (författare)
  • Occupational exposure to electromagnetic fields and sex-differential risk of uveal melanoma
  • 2010
  • Ingår i: Occupational and Environmental Medicine. - : BMJ. - 1470-7926 .- 1351-0711. ; 67:11, s. 751-759
  • Tidskriftsartikel (refereegranskat)abstract
    • Objectives The association between occupational exposure to electromagnetic fields (EMF) and the risk of uveal melanoma was investigated in a case-control study in nine European countries. Methods Incident cases of uveal melanoma and population as well as hospital controls were included and frequency matched by country, 5-year birth cohort and sex. Subjects were asked whether they had worked close to high-voltage electrical transmission installations, computer screens and various electrical machines, or in complex electrical environments. Measurements of two Scandinavian job-exposure matrices were applied to estimate lifelong cumulative EMF exposure. Unconditional logistic regression analyses, stratified by sex and eye colour were calculated, adjusting for several potential confounders. Results 293 patients with uveal melanoma and 3198 control subjects were interviewed. Women exposed to electrical transmission installations showed elevated risks (OR 5.81, 95% CI 1.72 to 19.66). Positive associations with exposure to control rooms were seen among men and women, but most risk increases were restricted to subjects with dark iris colour. Application of published EMF measurements revealed stronger risk increases among women compared to men. Again, elevated risks were restricted to subjects with dark eye colour. Conclusion Although based on a low prevalence of exposure to potential occupational sources of EMF, our data indicate that exposed dark-eyed women may be at particular risk for uveal melanoma.
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7.
  • Behrens, Thomas, et al. (författare)
  • Occupational exposure to endocrine-disrupting chemicals and the risk of uveal melanoma
  • 2012
  • Ingår i: Scandinavian Journal of Work, Environment and Health. - : Scandinavian Journal of Work, Environment and Health. - 0355-3140 .- 1795-990X. ; 38:5, s. 476-483
  • Tidskriftsartikel (refereegranskat)abstract
    • Objectives We investigated the association between occupational exposure to endocrine-disrupting chemicals (EDC) and the risk of uveal melanoma using international data of a case control study from nine European countries. Methods After exclusion of proxy interviews, 280 cases and 3084 control subjects were included in the final analysis. Information on possible exposure to EDC was derived from 27 job-specific questionnaires (JSQ), which solicited detailed questions on occupational tasks. Relative risk estimates were based on the JSQ and potential exposure to a group of endocrine-disrupting agents. We constructed several exposure scores, taking into account intensity of exposure, use of personal protective equipment, and exposure duration. We calculated unconditional logistic regression analyses, adjusting for country, age, sex, eye color and a history of ocular damage due to intense ultraviolet (UV) exposure. Results The overall exposure prevalence to EDC was low reaching a maximum of 11% for heavy metals with endocrine-disrupting properties. Although working in some industries was associated with increased melanoma risk [such as dry cleaning: odds ratio (OR) 6.15, 95% confidence interval (95% CI) 2.0-18.96 and working in the glass manufacturing industry: OR 3.49, 95% CI 1.10-11.10], agent-specific risks were not elevated. The strongest possible risk increase was observed for organic solvents with endocrine-disrupting properties (OR 1.31, 95% CI 0.78-2.21). Calculation of exposure scores did not indicate consistently elevated results with higher score values. Sensitivity analyses did not alter these results. Conclusion Occupational exposure to EDC was not associated with an increased risk for uveal melanoma.
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8.
  • Behrens, Thomas, et al. (författare)
  • Pesticide exposure in farming and forestry and the risk of uveal melanoma
  • 2012
  • Ingår i: Cancer Causes and Control. - : Springer. - 0957-5243 .- 1573-7225. ; 23:1, s. 141-151
  • Tidskriftsartikel (refereegranskat)abstract
    • Since pesticides are disputed risk factors for uveal melanoma, we studied the association between occupational pesticide exposure and uveal melanoma risk in a case-control study from nine European countries.Incident cases of uveal melanoma and population as well as hospital controls were included and frequency-matched by country, 5-year age groups and sex. Self-reported exposure was quantified with respect to duration of exposure and pesticide application method. We calculated the exposure intensity level based on application method and use of personal protective equipment. Odds ratios (OR) and 95% confidence intervals (95% CI) were estimated by unconditional logistic regression analyses and adjusted for several potential confounders.293 case and 3,198 control subjects were interviewed. We did not identify positive associations with activities in farming or forestry, pesticide application or pesticide mixing. No consistent positive associations were seen with exposure intensity level scores either. The only statistically significantly raised association in this study was for exposure to chemical fertilizers in forestry (OR = 8.93; 95% CI 1.73-42.13), but this observation was based on only six exposed subjects. Results did not change when we restricted analyses to morphologically verified cases and excluded proxy interviews as well as cancer controls. We did not observe effect modification by sex or eye color.Risk estimates for pesticide exposures and occupational activities in agriculture and forestry were not increased and did not indicate a hormonal mechanism due to these exposures.
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9.
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10.
  • Cook, Michael B, et al. (författare)
  • Tobacco and Alcohol in Relation to Male Breast Cancer: An Analysis of the Male Breast Cancer Pooling Project Consortium.
  • 2015
  • Ingår i: Cancer Epidemiology Biomarkers & Prevention. - 1538-7755. ; 24:3, s. 520-531
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: The etiology of male breast cancer is poorly understood, partly due to its relative rarity. Although tobacco and alcohol exposures are known carcinogens, their association with male breast cancer risk remains ill-defined. Methods: The Male Breast Cancer Pooling Project consortium provided 2,378 cases and 51,959 controls for analysis from 10 case-control and 10 cohort studies. Individual participant data were harmonized and pooled. Unconditional logistic regression was used to estimate study design-specific (case-control/cohort) odds ratios (OR) and 95% confidence intervals (CI), which were then combined using fixed effects meta-analysis. Results: Cigarette smoking status, smoking pack-years, duration, intensity, and age at initiation were not associated with male breast cancer risk. Relations with cigar and pipe smoking, tobacco chewing, and snuff use were also null. Recent alcohol consumption and average grams of alcohol consumed per day were also not associated with risk; only one sub-analysis of very high recent alcohol consumption (>60 grams/day) was tentatively associated with male breast cancer (ORunexposed referent=1.29, 95%CI:0.97-1.71; OR>0-<7 g/day referent=1.36, 95%CI:1.04-1.77). Specific alcoholic beverage types were not associated with male breast cancer. Relations were not altered when stratified by age or body mass index. Conclusions: In this analysis of the Male Breast Cancer Pooling Project we found little evidence that tobacco and alcohol exposures were associated with risk of male breast cancer. Impact: Tobacco and alcohol do not appear to be carcinogenic for male breast cancer. Future studies should aim to assess these exposures in relation to subtypes of male breast cancer.
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