Meta-analysis of genome-wide association studies identifies common susceptibility polymorphisms for colorectal and endometrial cancer near SH2B3 and TSHZ1
Authors: Cheng Timothy HT , Thompson Deborah , Painter Jodie , O’Mara Tracy , Gorman Maggie , Martin Lynn , Palles Claire , Jones Angela , Buchanan Daniel D. , Win Aung Ko , 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 MJ , 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 
Published: December 2015

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.