| 1. |
- Furberg, Helena, et al.
(författare)
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Genome-wide meta-analyses identify multiple loci associated with smoking behavior
- 2010
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Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1546-1718 .- 1061-4036. ; 42:5, s. 134-441
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Tidskriftsartikel (refereegranskat)abstract
- Consistent but indirect evidence has implicated genetic factors in smoking behavior1,2. We report meta-analyses of several smoking phenotypes within cohorts of the Tobacco and Genetics Consortium (n = 74,053). We also partnered with the European Network of Genetic and Genomic Epidemiology (ENGAGE) and Oxford-GlaxoSmithKline (Ox-GSK) consortia to follow up the 15 most significant regions (n > 140,000). We identified three loci associated with number of cigarettes smoked per day. The strongest association was a synonymous 15q25 SNP in the nicotinic receptor gene CHRNA3 (rs1051730[A], b = 1.03, standard error (s.e.) = 0.053, beta = 2.8 x 10(-73)). Two 10q25 SNPs (rs1329650[G], b = 0.367, s. e. = 0.059, beta = 5.7 x 10(-10); and rs1028936[A], b = 0.446, s. e. = 0.074, beta = 1.3 x 10(-9)) and one 9q13 SNP in EGLN2 (rs3733829[G], b = 0.333, s. e. = 0.058, P = 1.0 x 10(-8)) also exceeded genome-wide significance for cigarettes per day. For smoking initiation, eight SNPs exceeded genome-wide significance, with the strongest association at a nonsynonymous SNP in BDNF on chromosome 11 (rs6265[C], odds ratio (OR) = 1.06, 95% confidence interval (Cl) 1.04-1.08, P = 1.8 x 10(-8)). One SNP located near DBH on chromosome 9 (rs3025343[G], OR = 1.12, 95% Cl 1.08-1.18, P = 3.6 x 10(-8)) was significantly associated with smoking cessation.
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| 2. |
- McKay, James D., et al.
(författare)
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A Genome-Wide Association Study of Upper Aerodigestive Tract Cancers Conducted within the INHANCE Consortium
- 2011
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Ingår i: PLOS Genetics. - : Public Library of Science (PLoS). - 1553-7390 .- 1553-7404. ; 7:3
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Tidskriftsartikel (refereegranskat)abstract
- Genome-wide association studies (GWAS) have been successful in identifying common genetic variation involved in susceptibility to etiologically complex disease. We conducted a GWAS to identify common genetic variation involved in susceptibility to upper aero-digestive tract (UADT) cancers. Genome-wide genotyping was carried out using the Illumina HumanHap300 beadchips in 2,091 UADT cancer cases and 3,513 controls from two large European multi-centre UADT cancer studies, as well as 4,821 generic controls. The 19 top-ranked variants were investigated further in an additional 6,514 UADT cancer cases and 7,892 controls of European descent from an additional 13 UADT cancer studies participating in the INHANCE consortium. Five common variants presented evidence for significant association in the combined analysis (p <= 5 x 10(-7)). Two novel variants were identified, a 4q21 variant (rs1494961, p = 1 x 10(-8)) located near DNA repair related genes HEL308 and FAM175A (or Abraxas) and a 12q24 variant (rs4767364, p = 2 x 10(-8)) located in an extended linkage disequilibrium region that contains multiple genes including the aldehyde dehydrogenase 2 (ALDH2) gene. Three remaining variants are located in the ADH gene cluster and were identified previously in a candidate gene study involving some of these samples. The association between these three variants and UADT cancers was independently replicated in 5,092 UADT cancer cases and 6,794 controls non-overlapping samples presented here (rs1573496-ADH7, p = 5 x 10(-8); rs1229984-ADH1B, p = 7 x 10(-9); and rs698-ADH1C, p = 0.02). These results implicate two variants at 4q21 and 12q24 and further highlight three ADH variants in UADT cancer susceptibility.
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| 3. |
- Sandeck, Helmut P., et al.
(författare)
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Re-evaluation of histological diagnoses of malignant mesothelioma by immunohistochemistry
- 2010
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Ingår i: Diagnostic Pathology. - : Springer Science and Business Media LLC. - 1746-1596. ; 5, s. 47-
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Tidskriftsartikel (refereegranskat)abstract
- Background: In order to provide reliable tissue material for malignant mesothelioma (MM) studies, we re-evaluated biopsies and autopsy material from 61 patients with a diagnosis of MM from the period of 1980-2002. Methods: Basic positive (Calretinin, EMA, Podoplanin, Mesothelin) and negative (CEA, Ber-Ep4) immunohistochemical (IHC) marker reactions were determined. If needed, more markers were used. Histological diagnoses were made by three pathologists. Survival data were calculated. Results: 49 cases (80%) were considered being MM by a high degree of likelihood, five more cases possible MM. Of the remaining seven cases, three were diagnosed as adenocarcinoma, three as pleomorphic lung carcinoma, in one peritoneal case a clear entity diagnosis could not be given. One of the possible MM cases and two of the lung carcinoma cases had this already as primary diagnoses, but were registered as MM. With a sensitivity of 100%, Calretinin and CEA were the most reliable single markers. The amount of MM cells with positive immunoreactivity (IR) for Podoplanin and Mesothelin showed most reliable inverse relation to the degree of atypia. In the confirmed MM cases, there had been applied either no IHC or between one and 18 markers. The cases not confirmed by us had either lacked IHC (n = 1), non-specific markers were used (n = 4), IR was different (n = 1), or specific markers had not shown positive IR in the right part of the tumour cells (n = 3). 46 of the 49 confirmed and three of the not confirmed cases had been diagnosed by us as most likely MM before IHC was carried out. Conclusions: In order to use archival tissue material with an earlier MM diagnosis for studies, histopathological re-evaluation is important. In possible sarcomatous MM cases without any positive IR for positive MM markers, radiology and clinical picture are essential parts of diagnostics. IHC based on a panel of two positive and two negative MM markers has to be adapted to the differential diagnostic needs in each single case. New diagnostic tools and techniques are desirable for cases where IHC and other established methods cannot provide a clear entity diagnosis, and in order to improve MM treatment.
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| 4. |
- Talibov, Madar, et al.
(författare)
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Occupation and Leukemia in Nordic Countries
- 2012
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Ingår i: Journal of Occupational and Environmental Medicine. - : LIPPINCOTT WILLIAMS & WILKINS. - 1076-2752 .- 1536-5948. ; 54:12, s. 1527-1532
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Tidskriftsartikel (refereegranskat)abstract
- Objective: We studied occupational variation of the risk of acute myeloid leukemia, chronic lymphocytic leukemia, and other leukemia in Nordic countries. Methods: The study cohort comprised 15 million persons older than 30 years who participated in the population censuses in 1960, 1970, 1980/1981, 1990, or all of these years in five Nordic countries. Standardized incidence ratios (SIRs) were estimated for 53 occupations and one group of economically inactive persons. Results: Significantly increased risks were observed for acute myeloid leukemia among drivers (SIR = 1.16; 95% confidence interval [CI], 1.07-1.26) and food workers (SIR = 1.13; 95% CI, 1.01-1.27); for chronic lymphocytic leukemia among farmers (SIR = 1.09; 95% CI, 1.04-1.14) and clerical workers (SIR = 1.07; 95% CI, 1.01-1.14); and for other leukemia among seamen (SIR = 1.24; 95% CI, 1.04-1.49), "other health workers" (SIR = 1.22; 95% CI, 1.02-1.47), chemical process workers (SIR = 1.18; 95% CI, 1.01-1.38), and sales agents (SIR = 1.15; 95% CI, 1.06-1.25). Conclusion: Observed modest occupational variation of leukemia risk might be associated with occupational or lifestyle factors.
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| 5. |
- Talibov, Madar, et al.
(författare)
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Occupational exposure to solvents and acute myeloid leukemia : a population-based, case-control study in four Nordic countries
- 2014
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Ingår i: Scandinavian Journal of Work, Environment and Health. - : SCANDINAVIAN JOURNAL WORK ENVIRONMENT & HEALTH. - 0355-3140 .- 1795-990X. ; 40:5, s. 511-517
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Tidskriftsartikel (refereegranskat)abstract
- Objective The aim of the current study was to assess the relation between occupational exposure to solvents and the risk of acute myeloid leukemia (AML). Methods Altogether, this study comprises 15 332 incident cases of AML diagnosed in Finland, Norway, Sweden, and Iceland from 1961-2005 and 76 660 controls matched by year of birth, sex, and country. Occupational records were linked with Nordic Occupational Cancer Study job exposure matrix (JEM) to estimate quantitative values for 26 occupational exposure factors. Hazard ratios (HR) with 95% confidence intervals (95% CI) were estimated by using conditional logistic regression models. Results We did not observe statistically significantly increased risk for exposure to any of the solvents. HR estimates for high levels of toluene (HR 1.35, 95% CI 0.74-2.46), aromatic hydrocarbon solvents (ARHC) (HR 1.18, 95% CI 0.76-1.86), and moderate-to-high levels of trichloroethylene were slightly but non-significantly elevated. We did not observe an association between benzene exposure and AML in this study. Conclusions This study did not provide clear evidence for an association between occupational solvent exposure and AML. There was some indication for an excess risk in the groups of workers exposed to toluene, trichloroethylene, and ARHC.
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