- Title
- Meta-analysis of genome-wide association studies identifies common susceptibility polymorphisms for colorectal and endometrial cancer near SH2B3 and TSHZ1
- Creator
- Cheng, Timothy H. T.; Thompson, Deborah; Hopper, John; Tomlinson, Ian; Jenkins, Mark; Lindor, Noralane M.; Newcomb, Polly A.; Gallinger, Steve; Conti, David; Schumacher, Fred; Casey, Graham; Giles, Graham G.; Pharoah, Paul; Painter, Jodie; Peto, Julian; Cox, Angela; Swerdlow, Anthony; Couch, Fergus; Cunningham, Julie M.; Goode, Ellen L.; Winham, Stacey J.; Lambrechts, Diether; Fasching, Peter; Burwinkel, Barbara; O'Mara, Tracy; Brenner, Hermann; Brauch, Hiltrud; Chang-Claude, Jenny; Salvesen, Helga B.; Kristensen, Vessela; Darabi, Hatef; Li, Jingmei; Liu, Tao; Lindblom, Annika; Hall, Per; Gorman, Maggie; de Polanco, Magdalena Echeverry; Sans, Monica; Carracedo, Angel; Castellvi-Bel, Sergi; Rojas-Martinez, Augusto; Aguiar Jnr, Samuel; Teixeira, Manuel R.; Dunning, Alison M.; Dennis, Joe; Otton, Geoffrey; Martin, Lynn; Proietto, Tony; Holliday, Elizabeth; Attia, John; Ashton, Katie; Scott, Rodney J.; McEvoy, Mark; Dowdy, Sean C.; Fridley, Brooke L.; Werner, Henrica M. J.; Trovik, Jone; Palles, Claire; Njolstad, Tormund S.; Tham, Emma; Mints, Miriam; Runnebaum, Ingo; Hillemanns, Peter; Dörk, Thilo; Amant, Frederic; Schrauwen, Stefanie; Hein, Alexander; Beckmann, Matthias W.; Jones, Angela; Ekici, Arif; Czene, Kamila; Meindl, Alfons; Bolla, Manjeet K.; Michailidou, Kyriaki; Tyrer, Jonathan P.; Wang, Qin; Ahmed, Shahana; Healey, Catherine S.; Shah, Mitul; Buchanan, Daniel D.; Annibali, Daniela; Depreeuw, Jeroen; Al-Tassan, Nada A.; Harris, Rebecca; Meyer, Brian F.; Whiffin, Nicola; Hosking, Fay J.; Kinnersley, Ben; Farrington, Susan M.; Timofeeva, Maria; Ko Win, Aung; Tenesa, Albert; Campbell, Harry; Haile, Robert W.; Hodgson, Shirley; Carvajal-Carmona, Luis; Cheadle, Jeremy P.; Easton, Douglas; Dunlop, Malcolm; Houlston, Richard; Spurdle, Amanda
- Relation
- Scientific Reports Vol. 5, p. 17369-.
- Publisher Link
- http://dx.doi.org/10.1038/srep17369
- Publisher
- Nature Publishing Group
- Resource Type
- journal article
- Date
- 2015
- Description
- High-risk mutations in several genes predispose to both colorectal cancer (CRC) and endometrial cancer (EC). We therefore hypothesised that some lower-risk genetic variants might also predispose to both CRC and EC. Using CRC and EC genome-wide association series, totalling 13,265 cancer cases and 40,245 controls, we found that the protective allele [G] at one previously-identified CRC polymorphism, rs2736100 near TERT, was associated with EC risk (odds ratio (OR)=1.08, P=0.000167); this polymorphism influences the risk of several other cancers. A further CRC polymorphism near TERC also showed evidence of association with EC (OR=0.92; P=0.03). Overall, however, there was no good evidence that the set of CRC polymorphisms was associated with EC risk, and neither of two previously-reported EC polymorphisms was associated with CRC risk. A combined analysis revealed one genome-wide significant polymorphism, rs3184504, on chromosome 12q24 (OR=1.10, P=7.23×10⁻⁹) with shared effects on CRC and EC risk. This polymorphism, a missense variant in the gene SH2B3, is also associated with haematological and autoimmune disorders, suggesting that it influences cancer risk through the immune response. Another polymorphism, rs12970291 near gene TSHZ1, was associated with both CRC and EC (OR=1.26, P=4.82×10⁻⁸), with the alleles showing opposite effects on the risks of the two cancers.
- Subject
- high-risk mutations; CRC; cancer risk; genes
- Identifier
- http://hdl.handle.net/1959.13/1329594
- Identifier
- uon:26195
- Identifier
- ISSN:2045-2322
- Rights
- This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/
- Language
- eng
- Full Text
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