The NOD2 3020insC mutation and the risk of colorectal cancer.
Several predispositions to colorectal cancer have been identified, but little is known about genetic susceptibilities to disease in older persons. Colorectal cancer is a risk in Crohn's disease and is believed to be associated with an inappropriate inflammatory response. Recently, the NOD2 gene has been associated with Crohn's disease, which further strengthens the notion that the inflammatory response plays a crucial role in this disease. Several mutations have been identified in the NOD2 gene, which appear with significantly higher frequency in patients with the disease. One such mutation (3020insC) is believed to be clearly causative because it results in a prematurely truncated protein with a predicted reduction in functional efficiency. In this report, we have examined the frequency of the 3020insC mutation in a series of 856 individuals including 556 patients with colorectal cancer. The frequency of the 3020insC mutation in a consecutive series of 250 non-hereditary nonpolyposis colorectal cancer patients >50 years of age was significantly elevated compared with the control population (odds ratio, 2.23; P = 0.0046). The results indicate that NOD2 may be a predisposing factor to colorectal cancer characterized by an older average age of disease onset in persons who do not harbor any other genetic predisposition to disease.
Kurzawski
Grzegorz
G
International Hereditary Cancer Center, Department of Genetics and Pathology, Szczecin, Poland. gkurz@sci.pam.szczecin.pl
Suchy
Janina
J
Kładny
Józef
J
Grabowska
Ewa
E
Mierzejewski
Marek
M
Jakubowska
Anna
A
Debniak
Tadeusz
T
Cybulski
Cezary
C
Kowalska
Elsbieta
E
Szych
Zbigniew
Z
Domagała
Wenancjusz
W
Scott
Rodney J
RJ
Lubiński
Jan
J
D000328:Adult; D000368:Aged; D002352:Carrier Proteins / Q000235:genetics*; D015179:Colorectal Neoplasms / Q000209:etiology* / Q000235:genetics; D003424:Crohn Disease / Q000235:genetics*; D020022:Genetic Predisposition to Disease; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins; D008875:Middle Aged; D009154:Mutation; D053473:Nod2 Signaling Adaptor Protein; D012306:Risk
D002352:Carrier Proteins; D047908:Intracellular Signaling Peptides and Proteins; C429018:NOD2 protein, human; D053473:Nod2 Signaling Adaptor Protein