Carcinogenesis Advance Access originally published online on January 6, 2009
Carcinogenesis 2009 30(5):758-762; doi:10.1093/carcin/bgn286
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Genetic polymorphisms in the cytokine genes and risk of hepatocellular carcinoma in low-risk non-Asians of USA
1 Department of Pediatrics, Division of Pediatric Epidemiology and Clinical Research, University of Minnesota, MMC 715, 420 Delaware Street S.E., Minneapolis, MN 55455, USA
2 Masonic Cancer Center, University of Minnesota, Minneapolis, MN 55455, USA
* To whom correspondence should be addressed. Tel: +1 612 626 7625; Fax: +1 612 624 7147; Email: ognja001{at}umn.edu
Polymorphisms in cytokine genes responsible for inflammatory and immune responses are associated with risk of hepatocellular carcinoma (HCC) in high-risk Chinese population. Similar data in low-risk populations are lacking. A population-based case–control study of HCC was conducted including 120 HCC patients and 230 matched control subjects of non-Asian residents in Los Angeles County, California. Genetic variants in the interferon 
(IFN), tumor necrosis factor-
(TNF), interleukin-2 (IL-2), IL-4, IL-6, IL-10, IL-12 and IL-18 genes were determined by Taqman assays. The logistic regression method was used to analyze the data. For T helper (Th) 1 genes (IFN, IL-6 and IL-12), relative to the putative high-activity genotypes, individual low-activity genotypes were associated with statistically non-significant increases in HCC risk. The odds ratio (OR) was 1.53 [95% confidence interval (CI) = 0.53–4.39] for three versus zero low-activity genotypes. For Th2 cytokines (IL-4 and IL-10), low- versus high-activity genotypes were associated with statistically non-significant decreases in HCC risk. The OR was 0.64 (95% CI = 0.27–1.55) for two versus zero low-activity genotypes. When the Th1 and Th2 genotypes were examined simultaneously, the highest level of risk was observed in individuals jointly possessing the highest number of low-activity Th1 genotypes and the lowest number of low-activity Th2 genotypes. There was a roughly doubling of risk between these two extreme genetic profiles, which did not reach statistical significance (OR = 1.98, 95% CI = 0.50–7.84, P = 0.08). In contrast to high-risk Chinese, Th1 and Th2 genotypes did not impact in a major way on risk of HCC in USA non-Asians.
Abbreviations: CI, confidence interval; HBV, hepatitis B virus; HCV, hepatitis C virus; HCC, hepatocellular carcinoma; IFN, interferon ; IL, interleukin; OR, odds ratio; Th, T helper
Received November 7, 2008; revised November 7, 2008; accepted December 13, 2008.