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Single-nucleotide polymorphisms (SNPs) in cytokine genes can affect gene expression and thereby modulate inflammation and carcinogenesis. However, the data on the association between SNPs in the interleukin 1 beta gene ( IL1B ) and colorectal cancer (CRC) are conflicting. We found an association between a 4-SNP haplotype block of the  IL1B  (-3737C/-1464G/-511T/-31C) and CRC risk, and this association was exclusively observed in individuals with a higher proportion of African ancestry, such as individuals from the Coastal Colombian region (odds ratio, OR 2.06; 95% CI 1.31–3.25;  p  < 0.01). Moreover, a significant interaction between this CRC risk haplotype and local African ancestry dosage was identified in locus  2q14 (p  = 0.03). We conclude that Colombian individuals with high African ancestry proportions at locus  2q14  harbour more  IL1B-CGTC  copies and are consequently at an increased risk of CRC. This haplotype has been previously found to increase the  IL1B  promoter activity and is the most frequent haplotype in African Americans. Despite of limitations in the number of samples and the lack of functional analysis to examine the effect of these haplotypes on CRC cell lines, our results suggest that inflammation and ethnicity play a major role in the modulation of CRC risk.

IL1B-CGTC haplotype is associated with colorectal cancer in admixed individuals with increased African ancestry