No Association between Circulating Levels and Genetic Variants of IL-6 and TNF-alpha and Colon Adenoma
Abstract
Background: Interleukin 6 (IL-6) and tumor necrosis factor alpha (TNF-alpha), two important inflammatory cytokines, have been inconsistently associated with risk of colon neoplasia in epidemiological studies. However, research to date has not adequately assessed whether race-specific differences may exist in associations between biomarkers and genetic variants of these cytokines and colorectal adenoma - the precursor lesions of colorectal cancer. We sought to determine whether circulating levels of IL-6 and TNF-alpha, or genetic polymorphisms in IL-6and TNF-alpha were associated with colon adenoma and if so, whether that association differed by race.
Methods: We analyzed the associations of circulating levels and single nucleotide polymorphisms (SNPs) of IL-6 and TNF-alpha with risk of colon adenomas in a colonoscopy -based case-control study of 401 incident adenoma cases and 1,050 controls. We used multivariate unconditional logistic regression models to estimate the odds ratios (OR) and 95% confidence intervals (95% CI) for levels or genotypes (log additive models) of IL-6 and TNF-alpha.
Results: Compared to the bottom tertile of IL-6, the adjusted ORs were 1.06 (0.75 - 1.44) and 1.01 (0.72 - 1.40), respectively for the 2nd and 3rd tertiles (Ptrend = 0.10); the corresponding ORs for TNF-alpha were: 0.85 (0.63 - 1.15) and 1.01 (0.75 - 1.36), respectively (Ptrend = 0.39). Race-stratified analyses did not reveal any significant associations. There were also no statistically significant associations between IL-6 and TNF-alpha SNPs and colon adenoma.
Conclusions: Our results do not support pre-diagnostic levels of IL-6, TNF-alpha or their genetic variants as significant risk factors for the development of colon adenoma.
doi: http://dx.doi.org/10.4021/gr529w