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.
Original language | English (US) |
---|---|
Article number | 17369 |
Journal | Scientific reports |
Volume | 5 |
DOIs | |
State | Published - Dec 1 2015 |
ASJC Scopus subject areas
- General
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Meta-analysis of genome-wide association studies identifies common susceptibility polymorphisms for colorectal and endometrial cancer near SH2B3 and TSHZ1. / Cheng, Timothy H.T.; Thompson, Deborah; Painter, Jodie; Omara, Tracy; Gorman, Maggie; Martin, Lynn; Palles, Claire; Jones, Angela; Buchanan, Daniel D.; Ko Win, Aung; Hopper, John; Jenkins, Mark; Lindor, Noralane M.; Newcomb, Polly A.; Gallinger, Steve; Conti, David; Schumacher, Fred; Casey, Graham; Giles, Graham G.; Pharoah, Paul; Peto, Julian; Cox, Angela; Swerdlow, Anthony; Couch, Fergus; Cunningham, Julie M.; Goode, Ellen L.; Winham, Stacey J.; Lambrechts, Diether; Fasching, Peter; Burwinkel, Barbara; Brenner, Hermann; Brauch, Hiltrud; Chang-Claude, Jenny; Salvesen, Helga B.; Kristensen, Vessela; Darabi, Hatef; Li, Jingmei; Liu, Tao; Lindblom, Annika; Hall, Per; 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; 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; Njolstad, Tormund S.; Tham, Emma; Mints, Miriam; Runnebaum, Ingo; Hillemanns, Peter; Dörk, Thilo; Amant, Frederic; Schrauwen, Stefanie; Hein, Alexander; Beckmann, Matthias W.; Ekici, Arif; Czene, Kamila; Meindl, Alfons; Bolla, Manjeet K.; Michailidou, Kyriaki; Tyrer, Jonathan P.; Wang, Qin; Ahmed, Shahana; Healey, Catherine S.; Shah, Mitul; 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; Tenesa, Albert; Campbell, Harry; Haile, Robert W.; Hodgson, Shirley; Carvajal-Carmona, Luis; Cheadle, Jeremy P.; Easton, Douglas; Dunlop, Malcolm; Houlston, Richard; Spurdle, Amanda; Tomlinson, Ian.
In: Scientific reports, Vol. 5, 17369, 01.12.2015.Research output: Contribution to journal › Article › peer-review
}
TY - JOUR
T1 - Meta-analysis of genome-wide association studies identifies common susceptibility polymorphisms for colorectal and endometrial cancer near SH2B3 and TSHZ1
AU - Cheng, Timothy H.T.
AU - Thompson, Deborah
AU - Painter, Jodie
AU - Omara, Tracy
AU - Gorman, Maggie
AU - Martin, Lynn
AU - Palles, Claire
AU - Jones, Angela
AU - Buchanan, Daniel D.
AU - Ko Win, Aung
AU - Hopper, John
AU - Jenkins, Mark
AU - Lindor, Noralane M.
AU - Newcomb, Polly A.
AU - Gallinger, Steve
AU - Conti, David
AU - Schumacher, Fred
AU - Casey, Graham
AU - Giles, Graham G.
AU - Pharoah, Paul
AU - Peto, Julian
AU - Cox, Angela
AU - Swerdlow, Anthony
AU - Couch, Fergus
AU - Cunningham, Julie M.
AU - Goode, Ellen L.
AU - Winham, Stacey J.
AU - Lambrechts, Diether
AU - Fasching, Peter
AU - Burwinkel, Barbara
AU - Brenner, Hermann
AU - Brauch, Hiltrud
AU - Chang-Claude, Jenny
AU - Salvesen, Helga B.
AU - Kristensen, Vessela
AU - Darabi, Hatef
AU - Li, Jingmei
AU - Liu, Tao
AU - Lindblom, Annika
AU - Hall, Per
AU - De Polanco, Magdalena Echeverry
AU - Sans, Monica
AU - Carracedo, Angel
AU - Castellvi-Bel, Sergi
AU - Rojas-Martinez, Augusto
AU - Aguiar Jnr, Samuel
AU - Teixeira, Manuel R.
AU - Dunning, Alison M.
AU - Dennis, Joe
AU - Otton, Geoffrey
AU - Proietto, Tony
AU - Holliday, Elizabeth
AU - Attia, John
AU - Ashton, Katie
AU - Scott, Rodney J.
AU - McEvoy, Mark
AU - Dowdy, Sean C.
AU - Fridley, Brooke L.
AU - Werner, Henrica M.J.
AU - Trovik, Jone
AU - Njolstad, Tormund S.
AU - Tham, Emma
AU - Mints, Miriam
AU - Runnebaum, Ingo
AU - Hillemanns, Peter
AU - Dörk, Thilo
AU - Amant, Frederic
AU - Schrauwen, Stefanie
AU - Hein, Alexander
AU - Beckmann, Matthias W.
AU - Ekici, Arif
AU - Czene, Kamila
AU - Meindl, Alfons
AU - Bolla, Manjeet K.
AU - Michailidou, Kyriaki
AU - Tyrer, Jonathan P.
AU - Wang, Qin
AU - Ahmed, Shahana
AU - Healey, Catherine S.
AU - Shah, Mitul
AU - Annibali, Daniela
AU - Depreeuw, Jeroen
AU - Al-Tassan, Nada A.
AU - Harris, Rebecca
AU - Meyer, Brian F.
AU - Whiffin, Nicola
AU - Hosking, Fay J.
AU - Kinnersley, Ben
AU - Farrington, Susan M.
AU - Timofeeva, Maria
AU - Tenesa, Albert
AU - Campbell, Harry
AU - Haile, Robert W.
AU - Hodgson, Shirley
AU - Carvajal-Carmona, Luis
AU - Cheadle, Jeremy P.
AU - Easton, Douglas
AU - Dunlop, Malcolm
AU - Houlston, Richard
AU - Spurdle, Amanda
AU - Tomlinson, Ian
N1 - Funding Information: We are grateful for funding to the Oxford NIHR Comprehensive Biomedical Research Centre. Core funding to the Wellcome Trust Centre for Human Genetics was provided by the Wellcome Trust (090532/Z/09/Z). The European colorectal cancer data were supported by COST Action BM1206. We thank Breakthrough Breast Cancer and the Institute of Cancer Research for support and funding of the Breakthrough Generations Study, and the study participants, study staff, and the doctors, nurses and other health care providers and health information sources who have contributed to the study. We acknowledge NHS funding to the Royal Marsden/ICR NIHR Biomedical Research Centre. The Colon CFR was supported by grant UM1 CA167551 from the National Cancer Institute and through cooperative agreements with the following CCFR centres: Australasian Colorectal Cancer Family Registry, Mayo Clinic Cooperative Family Registry for Colon Cancer Studies, Ontario Familial Colorectal Cancer Registry, Seattle Colorectal Cancer Family Registry, USC Consortium Colorectal Cancer Family Registry. The Colon CFR GWAS was supported by funding from the National Cancer Institute, National Institutes of Health (U01 CA122839 and R01 CA143237 to Graham Casey). The content of this manuscript does not necessarily reflect the views or policies of the National Cancer Institute or any of the collaborating centres in the Colon Cancer Family Registry (CCFR), nor does mention of trade names, commercial products, or organizations imply endorsement by the US Government or the CCFR. Jeremy P. Cheadle was funded by the Bobby Moore Fund from Cancer Research UK, Tenovus, the Kidani Trust, Cancer Research Wales and the National Institute for Social Care and Health Research Cancer Genetics Biomedical Research Unit. Nada A. Al-Tassan and Brian F. Meyer were funded and supported by KFSHRC. Luis Carvajal-Carmona receives founding from The V Foundation for Cancer Research.The authors would also like to acknowledge The Australian Ovarian Cancer Study (AOCS) group. A full list of the participants and their affiliations appears in the suppplementary information file that is appended to this article.
PY - 2015/12/1
Y1 - 2015/12/1
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=84949294759&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84949294759&partnerID=8YFLogxK
U2 - 10.1038/srep17369
DO - 10.1038/srep17369
M3 - Article
C2 - 26621817
AN - SCOPUS:84949294759
VL - 5
JO - Scientific Reports
JF - Scientific Reports
SN - 2045-2322
M1 - 17369
ER -