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Träfflista för sökning "WFRF:(Hainaut Pierre) ;pers:(Boffetta Paolo)"

Sökning: WFRF:(Hainaut Pierre) > Boffetta Paolo

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  • Hung, Rayjean J, et al. (författare)
  • A susceptibility locus for lung cancer maps to nicotinic acetylcholine receptor subunit genes on 15q25
  • 2008
  • Ingår i: Nature. - : Nature Publishing Group. - 0028-0836 .- 1476-4687. ; 452:7187, s. 633-637
  • 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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3.
  • Krais, Annette M., et al. (författare)
  • Carcinogen-DNA Adducts
  • 2019. - Third Edition
  • Ingår i: Encyclopedia of Cancer. - 9780128124857 ; , s. 282-295
  • Bokkapitel (refereegranskat)abstract
    • Carcinogen-DNA adducts result from the covalent interaction of electrophilic chemical carcinogens with nucleophilic sites in DNA. Some highly reactive genotoxic carcinogens are capable of directly binding to DNA but most carcinogens require metabolic activation. DNA adducts, if not repaired, can lead to mutations, and mutations in critical genes are a characteristic feature of tumors. Thus DNA adduct formation is considered a critical step in the initiation of carcinogenesis. DNA adducts formed in human tissues can be detected by a variety of sensitive techniques including 32P-postlabeling, mass spectrometry, accelerator mass spectrometry, and immunoassays. Their detection and characterization in human tissues can provide clues on the etiology of human cancer.
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