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

Meta-analysis of genome-wide association studies identifies common susceptibility polymorphisms for colorectal and endometrial cancer near SH2B3 and TSHZ1. Cheng, T. H. T., Thompson, D., Painter, J., O'Mara, T., Gorman, M., Martin, L., Palles, C., Jones, A., Buchanan, D. D., Win, A. K., Hopper, J., Jenkins, M., Lindor, N. M., Newcomb, P. A., Gallinger, S., Conti, D., Schumacher, F., Casey, G., Giles, G. G., Pharoah, P., Peto, J., Cox, A., Swerdlow, A., Couch, F., Cunningham, J. M., Goode, E. L., Winham, S. J., Lambrechts, D., Fasching, P., Burwinkel, B., Brenner, H., Brauch, H., Chang-Claude, J., Salvesen, H. B., Kristensen, V., Darabi, H., Li, J., Liu, T., Lindblom, A., Hall, P., de Polanco, M. E., Sans, M., Carracedo, A., Castellvi-Bel, S., Rojas-Martinez, A., Aguiar Jnr, S., Teixeira, M. R., Dunning, A. M., Dennis, J., Otton, G., Proietto, T., Holliday, E., Attia, J., Ashton, K., Scott, R. J., McEvoy, M., Dowdy, S. C., Fridley, B. L., Werner, H. M. J., Trovik, J., Njolstad, T. S., Tham, E., Mints, M., Runnebaum, I., Hillemanns, P., Dörk, T., Amant, F., Schrauwen, S., Hein, A., Beckmann, M. W., Ekici, A., Czene, K., Meindl, A., Bolla, M. K., Michailidou, K., Tyrer, J. P., Wang, Q., Ahmed, S., Healey, C. S., Shah, M., Annibali, D., Depreeuw, J., Al-Tassan, N. A., Harris, R., Meyer, B. F., Whiffin, N., Hosking, F. J., Kinnersley, B., Farrington, S. M., Timofeeva, M., Tenesa, A., Campbell, H., Haile, R. W., Hodgson, S., Carvajal-Carmona, L., Cheadle, J. P., Easton, D., Dunlop, M., Houlston, R., Spurdle, A., & Tomlinson, I. Scientific Reports, 5:17369, 2015.
doi abstract bibtex

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.

@article{cheng_meta-analysis_2015,
	title = {Meta-analysis of genome-wide association studies identifies common susceptibility polymorphisms for colorectal and endometrial cancer near {SH2B3} and {TSHZ1}},
	volume = {5},
	issn = {2045-2322},
	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.},
	language = {eng},
	journal = {Scientific Reports},
	author = {Cheng, Timothy H. T. and Thompson, Deborah and Painter, Jodie and O'Mara, Tracy and Gorman, Maggie and Martin, Lynn and Palles, Claire and Jones, Angela and Buchanan, Daniel D. and Win, Aung Ko and Hopper, John and Jenkins, Mark and Lindor, Noralane M. and Newcomb, Polly A. and Gallinger, Steve and Conti, David and Schumacher, Fred and Casey, Graham and Giles, Graham G. and Pharoah, Paul and Peto, Julian and Cox, Angela and Swerdlow, Anthony and Couch, Fergus and Cunningham, Julie M. and Goode, Ellen L. and Winham, Stacey J. and Lambrechts, Diether and Fasching, Peter and Burwinkel, Barbara and Brenner, Hermann and Brauch, Hiltrud and Chang-Claude, Jenny and Salvesen, Helga B. and Kristensen, Vessela and Darabi, Hatef and Li, Jingmei and Liu, Tao and Lindblom, Annika and Hall, Per and de Polanco, Magdalena Echeverry and Sans, Monica and Carracedo, Angel and Castellvi-Bel, Sergi and Rojas-Martinez, Augusto and Aguiar Jnr, Samuel and Teixeira, Manuel R. and Dunning, Alison M. and Dennis, Joe and Otton, Geoffrey and Proietto, Tony and Holliday, Elizabeth and Attia, John and Ashton, Katie and Scott, Rodney J. and McEvoy, Mark and Dowdy, Sean C. and Fridley, Brooke L. and Werner, Henrica M. J. and Trovik, Jone and Njolstad, Tormund S. and Tham, Emma and Mints, Miriam and Runnebaum, Ingo and Hillemanns, Peter and Dörk, Thilo and Amant, Frederic and Schrauwen, Stefanie and Hein, Alexander and Beckmann, Matthias W. and Ekici, Arif and Czene, Kamila and Meindl, Alfons and Bolla, Manjeet K. and Michailidou, Kyriaki and Tyrer, Jonathan P. and Wang, Qin and Ahmed, Shahana and Healey, Catherine S. and Shah, Mitul and Annibali, Daniela and Depreeuw, Jeroen and Al-Tassan, Nada A. and Harris, Rebecca and Meyer, Brian F. and Whiffin, Nicola and Hosking, Fay J. and Kinnersley, Ben and Farrington, Susan M. and Timofeeva, Maria and Tenesa, Albert and Campbell, Harry and Haile, Robert W. and Hodgson, Shirley and Carvajal-Carmona, Luis and Cheadle, Jeremy P. and Easton, Douglas and Dunlop, Malcolm and Houlston, Richard and Spurdle, Amanda and Tomlinson, Ian},
	year = {2015},
	pmid = {26621817},
	pmcid = {PMC4664893},
	keywords = {Alleles, Colorectal Neoplasms, Endometrial Neoplasms, Female, Genetic Predisposition to Disease, Genome-Wide Association Study, Homeodomain Proteins, Humans, Intracellular Signaling Peptides and Proteins, Male, Neoplasm Proteins, Polymorphism, Genetic, Proteins},
	pages = {17369},
}

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