Meta-analysis of genome-wide association studies identifies common susceptibility polymorphisms for colorectal and endometrial cancer near SH2B3 and TSHZ1

Cheng THT, Thompson D, Painter J, O'Mara T, Gorman M, Martin L, Palles C, Jones A, Buchanan DD, Win AK, Hopper J, Jenkins M, Lindor NM, Newcomb PA, Gallinger S, Conti D, Schumacher F, Casey G, Giles GG, Pharoah P, Peto J, Cox A, Swerdlow A, Couch F, Cunningham JM, Goode EL, Winham SJ, Lambrechts D, Fasching PA, Burwinkel B, Brenner H, Brauch H, Chang-Claude J, Salvesen HB, Kristensen V, Darabi H, Li J, Liu T, Lindblom A, Hall P, Echeverry De Polanco M, Sans M, Carracedo A, Castellvi-Bel S, Rojas-Martinez A, Aguiar S, Teixeira MR, Dunning AM, Dennis J, Otton G, Proietto T, Holliday E, Attia J, Ashton K, Scott RJ, Mcevoy M, Dowdy SC, Fridley BL, Werner HMJ, Trovik J, Njolstad TS, Tham E, Mints M, Runnebaum I, Hillemanns P, Doerk T, Amant F, Schrauwen S, Hein A, Beckmann M, Ekici AB, Czene K, Meindl A, Bolla MK, Michailidou K, Tyrer JP, Wang Q, Ahmed S, Healey CS, Shah M, Annibali D, Depreeuw J, Al-Tassan NA, Harris R, Meyer BF, Whiffin N, Hosking FJ, Kinnersley B, Farrington SM, Timofeeva M, Tenesa A, Campbell H, Haile RW, Hodgson S, Carvajal-Carmona L, Cheadle JP, Easton D, Dunlop M, Houlston R, Spurdle A, Tomlinson I (2015)

Publication Type: Journal article

Publication year: 2015

Journal

Book Volume: 5

Pages Range: 17369

DOI: 10.1038/srep17369

Abstract

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.

Authors with CRIS profile

Involved external institutions

University Hospital Leuven (UZ) / Universitaire ziekenhuizen Leuven Belgium (BE) Katholieke Universiteit Leuven (KUL) / Catholic University of Leuven Belgium (BE) Karolinska Institute Sweden (SE) Technische Universität München (TUM) Germany (DE) University of Cambridge United Kingdom (GB) King Faisal Specialist Hospital & Research Centre Saudi Arabia (SA) Cardiff University United Kingdom (GB) University of Edinburgh United Kingdom (GB) Stanford University United States (USA) (US) St George's, University of London (SGUL) / St George's Hospital Medical School United Kingdom (GB) University of California Davis (UCDAVIS) United States (USA) (US) QIMR Berghofer Medical Research Institute (früher: the Queensland Institute of Medical Research) Australia (AU) University of Oxford United Kingdom (GB) Oslo University Hospital / Oslo Universitetssykehus Rikshospitalet Norway (NO) Instituto Português de Oncologia Francisco Gentil (IPO) / Portuguese Oncology Institute Portugal (PT) The University of Melbourne Australia (AU) Mayo Clinic United States (USA) (US) Fred Hutchinson Cancer Research Center United States (USA) (US) Mount Sinai Hospital (MSH) Canada (CA) University of Southern California (USC) United States (USA) (US) London School of Hygiene and Tropical Medicine United Kingdom (GB) University of Sheffield United Kingdom (GB) University College London (UCL) United Kingdom (GB) Deutsches Krebsforschungszentrum (DKFZ) Germany (DE) University of Bergen / Universitetet i Bergen Norway (NO) Universidad del Tolima Colombia (CO) University of the Republic / Universidad de la República (UdelaR) Uruguay (UY) Universidade de Santiago Compostela (USC) Spain (ES) Hospital Clínic de Barcelona Spain (ES) Universidad Autónoma de Nuevo León Mexico (MX) A.C.Camargo Cancer Center Brazil (BR) University of Newcastle (UoN) Australia (AU) John Hunter Hospital Australia (AU) University of Kansas (KU) United States (USA) (US) Friedrich-Schiller-Universität Jena Germany (DE) Medizinische Hochschule Hannover (MHH) / Hannover Medical School Germany (DE) University of California Los Angeles (UCLA) United States (USA) (US)

How to cite

APA:

Cheng, T.H.T., Thompson, D., Painter, J., O'Mara, T., Gorman, M., Martin, L.,... Tomlinson, I. (2015). Meta-analysis of genome-wide association studies identifies common susceptibility polymorphisms for colorectal and endometrial cancer near SH2B3 and TSHZ1. Scientific Reports, 5, 17369. https://doi.org/10.1038/srep17369

MLA:

Cheng, Timothy H. T., et al. "Meta-analysis of genome-wide association studies identifies common susceptibility polymorphisms for colorectal and endometrial cancer near SH2B3 and TSHZ1." Scientific Reports 5 (2015): 17369.

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