Common genetic variants at the CRAC1 (HMPS) locus on chromosome 15q13.3 influence colorectal cancer risk.
Jaeger E., Webb E., Howarth K., Carvajal-Carmona L., Rowan A., Broderick P., Walther A., Spain S., Pittman A., Kemp Z., Sullivan K., Heinimann K., Lubbe S., Domingo E., Barclay E., Martin L., Gorman M., Chandler I., Vijayakrishnan J., Wood W., Papaemmanuil E., Penegar S., Qureshi M., CORGI Consortium None., Farrington S., Tenesa A., Cazier J-B., Kerr D., Gray R., Peto J., Dunlop M., Campbell H., Thomas H., Houlston R., Tomlinson I.
We mapped a high-penetrance gene (CRAC1; also known as HMPS) associated with colorectal cancer (CRC) in the Ashkenazi population to a 0.6-Mb region on chromosome 15 containing SCG5 (also known as SGNE1), GREM1 and FMN1. We hypothesized that the CRAC1 locus harbored low-penetrance variants that increased CRC risk in the general population. In a large series of colorectal cancer cases and controls, SNPs near GREM1 and SCG5 were strongly associated with increased CRC risk (for rs4779584, P = 4.44 x 10(-14)).