TY - JOUR
T1 - Investigation of the colorectal cancer susceptibility region on chromosome 8q24.21 in a large German case-control sample
AU - Schafmayer, Clemens
AU - Buch, Stephan
AU - Völzke, Henry
AU - Von Schönfels, Witigo
AU - Egberts, Jan Hendrik
AU - Schniewind, Bodo
AU - Brosch, Mario
AU - Ruether, Andreas
AU - Franke, Andre
AU - Mathiak, Micaela
AU - Sipos, Bence
AU - Henopp, Tobias
AU - Catalcali, Jasmin
AU - Hellmig, Stephan
AU - Elsharawy, Abdou
AU - Katalinic, Alexander
AU - Lerch, Markus M.
AU - John, Ulrich
AU - Fölsch, Ulrich R.
AU - Fändrich, Fred
AU - Kalthoff, Holger
AU - Schreiber, Stefan
AU - Krawczak, Michael
AU - Tepel, Jürgen
AU - Hampe, Jochen
PY - 2009/1/1
Y1 - 2009/1/1
N2 - Human chromosome 8q24.21 has been implicated as a susceptibility region for colorectal cancer (CRC) as a result of genome-wide association and candidate gene studies. To assess the impact of molecular variants at 8q24.21 upon the CRC risk of German individuals and to refine the disease-associated region, a total of 2,713 patients with operated CRC (median age at diagnosis: 63 years) were compared with 2,718 sex-matched control individuals (median age at inclusion: 65 years). Information on microsatellite instability in tumors was available for 901 patients. Association analysis of SNPs rs10505477 and rs6983267 yielded allelic p-values of 1.42 × 10-7 and 2.57 × 10 -7, respectively. For both polymorphisms, the odds ratio was estimated to be 1.50 (95% Cl: 1.29-1.75) under a recessive disease model. The strongest candidate interval, outside of which significance dropped by more than 4 orders of magnitude, was delineated by SNPs rs10505477 and rs7014346 and comprised 17 kb. In a subgroup analysis, the disease association was found to be more pronounced in MSI-stable tumors (odds ratio: 1.71). Our study confirms the role of genetic variation at 8q24.21 as a risk factor for CRC and localizes the corresponding susceptibility gene to a 17 kb candidate region.
AB - Human chromosome 8q24.21 has been implicated as a susceptibility region for colorectal cancer (CRC) as a result of genome-wide association and candidate gene studies. To assess the impact of molecular variants at 8q24.21 upon the CRC risk of German individuals and to refine the disease-associated region, a total of 2,713 patients with operated CRC (median age at diagnosis: 63 years) were compared with 2,718 sex-matched control individuals (median age at inclusion: 65 years). Information on microsatellite instability in tumors was available for 901 patients. Association analysis of SNPs rs10505477 and rs6983267 yielded allelic p-values of 1.42 × 10-7 and 2.57 × 10 -7, respectively. For both polymorphisms, the odds ratio was estimated to be 1.50 (95% Cl: 1.29-1.75) under a recessive disease model. The strongest candidate interval, outside of which significance dropped by more than 4 orders of magnitude, was delineated by SNPs rs10505477 and rs7014346 and comprised 17 kb. In a subgroup analysis, the disease association was found to be more pronounced in MSI-stable tumors (odds ratio: 1.71). Our study confirms the role of genetic variation at 8q24.21 as a risk factor for CRC and localizes the corresponding susceptibility gene to a 17 kb candidate region.
UR - http://www.scopus.com/inward/record.url?scp=58149386907&partnerID=8YFLogxK
U2 - 10.1002/ijc.23872
DO - 10.1002/ijc.23872
M3 - Journal articles
C2 - 18839428
AN - SCOPUS:58149386907
SN - 0020-7136
VL - 124
SP - 75
EP - 80
JO - International Journal of Cancer
JF - International Journal of Cancer
IS - 1
ER -
