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A susceptibility locus for lung cancer maps to nicotinic acetylcholine receptor subunit genes on 15q25
| Content Provider | Semantic Scholar |
|---|---|
| Author | Hung, Rayjean J. McKay, James D. Gaborieau, Valérie Boffetta, Paolo Hashibe, Mia Zaridze, David Mukeria, Anush Szeszenia-Dabrowska, Neonilia Lissowska, Jolanta Rudnai, Péter Fabiánová, Eleonóra Mates, Dana Bencko, Vladimír Foretová, Lenka Janout, Vladimír Chen, Chu Goodman, Gary E. Field, John K. Liloglou, Triantafillos Xinarianos, George Cassidy, Adrian McLaughlin, John Liu, Geoffrey Narod, Steven A. Krokan, Hans Einar Skorpen, Frank Elvestad, Maiken Bratt Hveem, Kristian Vatten, Lars Linseisen, Jakob Clavel-Chapelon, Françoise Vineis, Paolo Bueno-De-Mesquita, H. B. As Lund, Eiliv Martı́nez, Carmen Bingham, Sa Rasmuson, Torgny Hainaut, P. Riboli, Elio Ahrens, Wolfgang Benhamou, Simone Lagiou, Pagona Trichopoulos, Dimitrios Holcatova, Ivana Merletti, Franco Kjaerheim, Kristina Agudo, Antonio Macfarlane, Gary John Talamini, Renato Simonato, Lorenzo Lowry, Ray Conway, David Ian Znaor, Ariana Healy, Claire M. Zélénika, Diana Boland, Anne Delépine, Marc Foglio, Mario Eusébio Lechner, Doris Matsuda, Fumihiko Blanché, Hélène Heath, Simon Lathrop, Mark Brennan, Paul |
| Copyright Year | 2008 |
| 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 × 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 × 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. |
| Starting Page | 633 |
| Ending Page | 637 |
| Page Count | 5 |
| File Format | PDF HTM / HTML |
| DOI | 10.1038/nature06885 |
| PubMed reference number | 18385738 |
| Journal | Medline |
| Volume Number | 452 |
| Alternate Webpage(s) | https://iris.unito.it/retrieve/handle/2318/102453/5671/nature06885.pdf |
| Alternate Webpage(s) | http://www.tara.tcd.ie/bitstream/handle/2262/67628/A%20susceptibility%20locus%20.pdf;jsessionid=E3F66D14F4CD27257FA9DB289DDB83DF?sequence=1 |
| Alternate Webpage(s) | http://homes.mpimf-heidelberg.mpg.de/~mhelmsta/pdf/2008%20Hung%20..%20Brennan%20Nature.pdf |
| Alternate Webpage(s) | http://www.tara.tcd.ie/bitstream/handle/2262/67628/A%20susceptibility%20locus%20.pdf?isAllowed=y&sequence=1 |
| Alternate Webpage(s) | https://doi.org/10.1038/nature06885 |
| Journal | Nature |
| Language | English |
| Access Restriction | Open |
| Content Type | Text |
| Resource Type | Article |
