Abstract
BackgroundColorectal cancer (CRC) is one of the most common cancers worldwide, and genetic variations exert distinct roles in its pathogenesis. Single nucleotide polymorphisms (SNPs) in interleukin 1 alpha (IL1A) were reported to be correlated to the susceptibility of diverse cancers. The aim of this study was to assess the association of IL1A SNPs with the risk of colorectal cancer in a Chinese Han population.MethodsTo evaluate the correlation between IL1A polymorphisms and CRC risk, Agena MassARRAY platform was used for genotype determination among 248 CRC patients and 463 controls. The relationships between IL1A variants and CRC susceptibility were examined by logistic regression analysis. Stratified analysis was conducted for the association detection in males and females. Haplotype construction and analysis were applied to evaluate the potential relationship between the genetic block and the risk of CRC. SNP functional exploration was performed with available bioinformatics datasets.ResultsAfter adjusting for age and gender, the “AA” genotype of rs2856838 exhibited a risk association with colorectal cancer in the recessive model (adjusted OR = 1.98, 95% CI: 1.05–3.72, p = 0.036). With stratified analysis, the recessive models of rs3783550 (OR = 2.17, 95% CI: 1.03–4.60, p = 0.043), rs2856838 (OR = 2.58, 95% CI: 1.13–5.87, p = 0.024), rs1609682 (OR = 2.20, 95% CI: 1.04–4.65, p = 0.040), and rs3783521 (OR = 2.13, 95% CI: 1.01–4.49, p = 0.048) revealed significant relationships between these variants and an increased CRC risk only in females. Bioinformatics analysis also revealed the putative functions of the selected SNPs.ConclusionsThis study demonstrated that rs2856838 could influence the susceptibility to CRC in Chinese Han population from northwest China. IL1A variants rs3783550, rs2856838, rs1609682, and rs3783521 were associated with CRC risk only in females.
Highlights
Colorectal cancer (CRC) is one of the most common cancers worldwide, and genetic variations exert distinct roles in its pathogenesis
We investigated the effects of five interleukin 1 alpha (IL1A) variants on the susceptibility to CRC, which is supposed to provide more evidence for IL1A in CRC pathogenesis and contribute to early CRC risk estimation among the individuals of Chinese Han ancestry
Population characteristics The demographic information of the enrolled CRC patients and healthy controls are listed in Additional file 1: Table S2
Summary
Colorectal cancer (CRC) is one of the most common cancers worldwide, and genetic variations exert distinct roles in its pathogenesis. Single nucleotide polymorphisms (SNPs) in interleukin 1 alpha (IL1A) were reported to be correlated to the susceptibility of diverse cancers. The aim of this study was to assess the association of IL1A SNPs with the risk of colorectal cancer in a Chinese Han population. Inflammatory and tumour cells could produce cytokines and chemokines that facilitate tumour promotion and progression [6]. Together with IL-1β, IL-1α, encoded by IL1A (interleukin 1 alpha), is defined as an “alarm cytokine” that belongs to IL-1 cluster and plays dual roles in malignant tumour progression [22]. Secretable form of IL-1α in the microenvironment of tumour cells has been proved to facilitate tumour invasiveness and angiogenesis [21]
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