Lack of association between genetic polymorphisms in cytokine genes and disease expression in patients with hereditary non-polyposis colorectal cancer.
OBJECTIVE
Hereditary non-polyposis colorectal cancer (HNPCC) is caused by germline mutations in DNA mismatch repair (MMR) genes and is characterized by familial aggregations of early-onset epithelial cancers. Inflammatory cells produce an attractive environment for tumour growth since reactive oxygen and nitrogen species generated by inflammatory cytokine induction can cause damage to DNA and proteins. In this study the objective was to investigate single nucleotide polymorphisms (SNPs) in cytokine genes to assess their impact on disease expression in individuals diagnosed with HNPCC.


METHODS
DNA samples from 220 participants diagnosed with HNPCC were genotyped for SNPs in IL-6, IL-1beta, TNF-alpha, IFN-gamma, IL-10, IL-4 and IL-1RN. The association between the polymorphisms and disease characteristics, i.e. affected or unaffected with colorectal cancer (CRC) and age of diagnosis of CRC, was tested with the Pearson chi2 test and by Kaplan-Meier survival analysis.


RESULTS
There was no significant difference between CRC patients and unaffected MMR gene mutation carriers for any of the SNPs studied and the Kaplan-Meier survival analysis showed no significant difference between age of diagnosis of CRC and genotype.


CONCLUSIONS
The SNPs selected for this study do not appear to modify disease expression in HNPCC. Given the complexity of the inflammatory response, the limited number of SNPs studied does not rule out the notion that other cytokine polymorphisms could act as disease modifiers of disease expression in HNPCC.
Talseth
Bente A
BA
Discipline of Medical Genetic, Faculty of Health, University of Newcastle, and the Hunter Medical Research Institute, NSW, Australia.
Meldrum
Cliff
C
Suchy
Janina
J
Kurzawski
Grzegroz
G
Lubinski
Jan
J
Scott
Rodney J
RJ
D003123:Colorectal Neoplasms, Hereditary Nonpolyposis / Q000453:epidemiology / Q000235:genetics* / Q000378:metabolism; D016207:Cytokines / Q000235:genetics*; D053843:DNA Mismatch Repair; D004273:DNA, Neoplasm / Q000235:genetics*; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D005838:Genotype; D018095:Germ-Line Mutation; D006801:Humans; D015994:Incidence; D008297:Male; D008875:Middle Aged; D009517:New South Wales / Q000453:epidemiology; D011044:Poland / Q000453:epidemiology; D016133:Polymerase Chain Reaction; D011110:Polymorphism, Genetic; D011379:Prognosis; D015996:Survival Rate / Q000639:trends
D016207:Cytokines; D004273:DNA, Neoplasm