Carcinogenesis Advance Access published online on April 30, 2008
Carcinogenesis, doi:10.1093/carcin/bgn101
Interleukin Promoter Polymorphisms and Prognosis in Colorectal Cancer
1 Division of Molecular Genetic Epidemiology, German Cancer Research Center (DKFZ), Heidelberg, Germany
2 Department of Oncology, Norrlands University Hospital, Umeå, Sweden
3 Department of Public Health and Clinical Medicine/Nutritional Research, Umeå University, Sweden
4 Department of Medical Biosciences, Umeå University, Sweden
5 Center for Family and Community Medicine, Karolinska Institute, Huddinge, Sweden
* Corresponding author: Asta Försti, German Cancer Research Center (DKFZ), Molecular Genetic Epidemiology, Im Neuenheimer Feld 580, 69120 Heidelberg, Germany Tel.: +49-6221-421803, Fax: +49-6221-421810, E-mail: a.foersti{at}dkfz.de
There is strong evidence that cancer associated inflammation promotes tumor growth and progression. This is especially true for colorectal cancer (CRC). Interleukins (ILs) are important modulators for inflammation. We examined whether promoter polymorphisms in key IL genes (IL4, IL4R, IL6, IL8, IL10) are associated with the risk or clinical outcome of CRC. Five single nucleotide polymorphisms (SNPs) were analyzed in genomic DNA from a cohort including 308 Swedish incident cases of CRC with data on Dukes’ stage and up to 16 years of follow-up, and 585 healthy controls. The selected SNPs have previously been shown to be functional and/or associated with cancer. None of the analyzed SNPs associated with the risk of CRC. When stratifying by tumor stage, significantly more patients carrying at least one G allele of IL10-1082 had tumors with Dukes’ stages A+B than with stages C+D (ptrend=0.035 for genotype distribution). Analyzing associations with overall survival time, we found the rare T allele of IL4-590 to be related to a longer survival [CT vs. CC Cox proportional hazard ratio (HR) 0.69, 95% confidence intervals (CIs) 0.46-1.03; TT vs. CC 0.32 (0.10-1.03)]. For IL6-174, the CG genotype was associated with a longer survival when compared to the CC genotype [0.64 (0.40-1.01)]. The present study was particularly suitable for survival analysis, because all patients were sampled before the diagnosis of CRC. Our results suggest that the SNPs IL4-590 and IL6-174 may be useful markers for CRC prognosis. The predicted biological effect of these SNPs in relation to promotion of cancer progression is consistent with the observed increased survival time.
Received January 23, 2008; revised April 7, 2008; accepted April 18, 2008.