Carcinogenesis Advance Access originally published online on April 30, 2008
Carcinogenesis 2008 29(6):1202-1206; doi:10.1093/carcin/bgn101
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Interleukin promoter polymorphisms and prognosis in colorectal cancer
1 Division of Molecular Genetic Epidemiology, German Cancer Research Center (DKFZ), Im Neuenheimer Feld 580, 69120 Heidelberg, Germany
2 Department of Oncology, Norrlands University Hospital, 90187 Umeå, Sweden
3 Department of Public Health and Clinical Medicine/Nutritional Research
4 Department of Medical Biosciences, Umeå University, 90185 Umeå, Sweden
5 Center for Family and Community Medicine, Karolinska Institute, 14183 Huddinge, Sweden
* To whom correspondence should be addressed. Tel: +49 6221 421803; Fax: +49 6221 421810; Email: 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 and 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 versus CC Cox proportional hazard ratio 0.69, 95% confidence intervals 0.46–1.03, TT versus CC 0.32 (0.10–1.03)]. For IL6-174, the CG genotype was associated with a longer survival when compared with 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.
Abbreviations: CI, confidence interval; CRC, colorectal cancer; HR, hazard ratio; IL, interleukin; OR, odds ratio; SNP, single-nucleotide polymorphism
Received January 23, 2008; revised April 7, 2008; accepted April 18, 2008.
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