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

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 Ht

AU - Thompson, Deborah

AU - Painter, Jodie

AU - O'Mara, 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 Mj

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

PY - 2015

Y1 - 2015

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.

U2 - 10.1038/srep17369

DO - 10.1038/srep17369

M3 - SCORING: Journal article

C2 - 26621817

VL - 5

SP - 17369

JO - SCI REP-UK

JF - SCI REP-UK

SN - 2045-2322

ER -