Common variation near CDKN1A, POLD3 and SHROOM2 influences colorectal cancer risk.
Dunlop MG., Dobbins SE., Farrington SM., Jones AM., Palles C., Whiffin N., Tenesa A., Spain S., Broderick P., Ooi L-Y., Domingo E., Smillie C., Henrion M., Frampton M., Martin L., Grimes G., Gorman M., Semple C., Ma YP., Barclay E., Prendergast J., Cazier J-B., Olver B., Penegar S., Lubbe S., Chander I., Carvajal-Carmona LG., Ballereau S., Lloyd A., Vijayakrishnan J., Zgaga L., Rudan I., Theodoratou E., Colorectal Tumour Gene Identification (CORGI) Consortium None., Starr JM., Deary I., Kirac I., Kovacević D., Aaltonen LA., Renkonen-Sinisalo L., Mecklin J-P., Matsuda K., Nakamura Y., Okada Y., Gallinger S., Duggan DJ., Conti D., Newcomb P., Hopper J., Jenkins MA., Schumacher F., Casey G., Easton D., Shah M., Pharoah P., Lindblom A., Liu T., Swedish Low-Risk Colorectal Cancer Study Group None., Smith CG., West H., Cheadle JP., COIN Collaborative Group None., Midgley R., Kerr DJ., Campbell H., Tomlinson IP., Houlston RS.
We performed a meta-analysis of five genome-wide association studies to identify common variants influencing colorectal cancer (CRC) risk comprising 8,682 cases and 9,649 controls. Replication analysis was performed in case-control sets totaling 21,096 cases and 19,555 controls. We identified three new CRC risk loci at 6p21 (rs1321311, near CDKN1A; P = 1.14 × 10(-10)), 11q13.4 (rs3824999, intronic to POLD3; P = 3.65 × 10(-10)) and Xp22.2 (rs5934683, near SHROOM2; P = 7.30 × 10(-10)) This brings the number of independent loci associated with CRC risk to 20 and provides further insight into the genetic architecture of inherited susceptibility to CRC.