Inflammatory response gene polymorphisms and their relationship with colorectal cancer risk.
BACKGROUND
Patients with chronic inflammatory bowel disease (IBD) are at an increased risk of colorectal cancer (CRC) and it is estimated that one in six persons diagnosed with IBD will develop CRC. This fact suggests that genetic variations in inflammatory response genes may act as CRC disease risk modifiers.


METHODS
In order to test this hypothesis we investigated a series of polymorphisms in 6 genes (NOD2, DLG5, OCTN1, OCTN2, IL4, TNFalpha) associated with the inflammatory response on a group of 607 consecutive newly diagnosed colorectal cancer patients and compared the results to controls (350 consecutive newborns and 607 age, sex and geographically matched controls).


RESULTS
Of the six genes only one polymorphism in TNFalpha(-1031T/T) showed any tendency to be associated with disease risk (64.9% for controls and 71.4% for CRC) which we further characterized on a larger cohort of CRC patients and found a more profound relationship between the TNFalpha -1031T/T genotype and disease (64.5% for controls vs 74.7% for CRC cases above 70 yrs). Then, we investigated this result and identified a suggestive tendency, linking the TNFalpha -1031T/T genotype and a previously identified change in the CARD15/NOD2 gene (OR = 1.87; p = 0,02 for CRC cases above 60 yrs).


CONCLUSIONS
The association of polymorphisms in genes involved in the inflammatory response and CRC onset suggest that there are genetic changes capable of influencing disease risk in older persons.
Suchy
Janina
J
International Hereditary Cancer Center-Department of Genetics and Pathology, Pomeranian Medical University, Szczecin, Poland. jansuch@interia.pl
Kłujszo-Grabowska
Ewa
E
Kładny
Józef
J
Cybulski
Cezary
C
Wokołorczyk
Dominika
D
Szymańska-Pasternak
Jolanta
J
Kurzawski
Grzegorz
G
Scott
Rodney J
RJ
Lubiński
Jan
J
D000328:Adult; D000367:Age Factors; D000368:Aged; D000369:Aged, 80 and over; D016022:Case-Control Studies; D015179:Colorectal Neoplasms / Q000209:etiology / Q000235:genetics*; D005260:Female; D020022:Genetic Predisposition to Disease; D005820:Genetic Testing; D006801:Humans; D015212:Inflammatory Bowel Diseases / Q000150:complications / Q000235:genetics*; D015847:Interleukin-4 / Q000235:genetics; D008297:Male; D008565:Membrane Proteins / Q000235:genetics; D008875:Middle Aged; D053473:Nod2 Signaling Adaptor Protein / Q000235:genetics; D027701:Organic Cation Transport Proteins / Q000235:genetics; D011110:Polymorphism, Genetic; D012307:Risk Factors; D000074058:Solute Carrier Family 22 Member 5; D027981:Symporters; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics*; D025521:Tumor Suppressor Proteins / Q000235:genetics
C114461:DLG5 protein, human; D008565:Membrane Proteins; C429018:NOD2 protein, human; D053473:Nod2 Signaling Adaptor Protein; D027701:Organic Cation Transport Proteins; C109807:SLC22A4 protein, human; C492020:SLC22A5 protein, human; D000074058:Solute Carrier Family 22 Member 5; D027981:Symporters; D014409:Tumor Necrosis Factor-alpha; D025521:Tumor Suppressor Proteins; D015847:Interleukin-4