Investigation of the colorectal cancer susceptibility region on chromosome 8q24.21 in a large German case-control sample.
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 x 10(-7) and 2.57 x 10(-7), respectively. For both polymorphisms, the odds ratio was estimated to be 1.50 (95% CI: 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.
Department of General and Thoracic Surgery, University Hospital Schleswig-Holstein, Kiel, Germany.
Clemens
C
Schafmayer
Stephan
S
Buch
Henry
H
Völzke
Witigo
W
von Schönfels
Jan Hendrik
JH
Egberts
Bodo
B
Schniewind
Mario
M
Brosch
Andreas
A
Ruether
Andre
A
Franke
Micaela
M
Mathiak
Bence
B
Sipos
Tobias
T
Henopp
Jasmin
J
Catalcali
Stephan
S
Hellmig
Abdou
A
ElSharawy
Alexander
A
Katalinic
Markus M
MM
Lerch
Ulrich
U
John
Ulrich R
UR
Fölsch
Fred
F
Fändrich
Holger
H
Kalthoff
Stefan
S
Schreiber
Michael
M
Krawczak
Jürgen
J
Tepel
Jochen
J
Hampe
D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D016022:Case-Control Studies; D002898:Chromosomes, Human, Pair 8; D015179:Colorectal Neoplasms / Q000175:diagnosis / Q000453:epidemiology* / Q000235:genetics*; D005260:Female; D020022:Genetic Predisposition to Disease; D005858:Germany; D006801:Humans; D008297:Male; D018895:Microsatellite Repeats; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide