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- Hung, Rayjean J, et al.
(författare)
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A susceptibility locus for lung cancer maps to nicotinic acetylcholine receptor subunit genes on 15q25
- 2008
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Ingår i: Nature. - : Nature Publishing Group. - 0028-0836 .- 1476-4687. ; 452:7187, s. 633-637
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Tidskriftsartikel (refereegranskat)abstract
- Lung cancer is the most common cause of cancer death worldwide, with over one million cases annually. To identify genetic factors that modify disease risk, we conducted a genome-wide association study by analysing 317,139 single-nucleotide polymorphisms in 1,989 lung cancer cases and 2,625 controls from six central European countries. We identified a locus in chromosome region 15q25 that was strongly associated with lung cancer (P = 9 x 10(-10)). This locus was replicated in five separate lung cancer studies comprising an additional 2,513 lung cancer cases and 4,752 controls (P = 5 x 10(-20) overall), and it was found to account for 14% (attributable risk) of lung cancer cases. Statistically similar risks were observed irrespective of smoking status or propensity to smoke tobacco. The association region contains several genes, including three that encode nicotinic acetylcholine receptor subunits (CHRNA5, CHRNA3 and CHRNB4). Such subunits are expressed in neurons and other tissues, in particular alveolar epithelial cells, pulmonary neuroendocrine cells and lung cancer cell lines, and they bind to N'-nitrosonornicotine and potential lung carcinogens. A non-synonymous variant of CHRNA5 that induces an amino acid substitution (D398N) at a highly conserved site in the second intracellular loop of the protein is among the markers with the strongest disease associations. Our results provide compelling evidence of a locus at 15q25 predisposing to lung cancer, and reinforce interest in nicotinic acetylcholine receptors as potential disease candidates and chemopreventative targets.
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- Jansson, C, et al.
(författare)
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Relation between gastroesophageal reflux symptoms and socioeconomic factors : a population-based study (the HUNT Study)
- 2007
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Ingår i: Clinical Gastroenterology and Hepatology. - : Elsevier BV. - 1542-3565 .- 1542-7714. ; 5:9, s. 1029-1034
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND & AIMS: Gastroesophageal reflux constitutes a major public health problem in the Western world. Few population-based studies have addressed socioeconomic factors in relation to reflux. METHODS: We conducted a case-control study based on 2 health surveys performed in the Norwegian county of Nord-Trondelag in 1984-1986 and 1995-1997, respectively. Reflux was assessed in the second survey, comprising 65,333 participants representing 70% of the county's adult population. Among 58,596 persons responding to questions regarding reflux symptoms, 3153 persons reporting severe symptoms represented the cases, and 40,210 persons without symptoms represented the controls. Data collected in questionnaires included socioeconomic status (SES) based on occupation, education, and material deprivation; family situation; and potential confounders. Odds ratios (ORs) with 95% confidence intervals (CIs) were estimated from unconditional logistic regression in crude models and models adjusted for age, sex, smoking, and body mass. RESULTS: The risk of reflux increased with decreasing levels of SES based on occupation, education, and material deprivation. Increased risks of reflux were seen among unskilled laborers (OR, 1.6; 95% CI, 1.3-2.0), skilled laborers (OR, 1.4; 95% CI, 1.1-1.7), and self-employed and farmers (OR, 1.3; 95% CI, 1.1-1.6). A 1.9-fold (95% CI, 1.7-2.2) increased risk of reflux was observed among persons with low education, compared with highly educated persons. Reflux was more common among materially deprived persons (OR, 3.4; 95% CI, 2.9-4.1). The results were similar in crude and adjusted models. CONCLUSIONS: This large population-based study reveals a link between low SES and reflux symptoms that is not explained by the known risk factors of smoking or obesity. This finding deserves further research.
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