Genetic polymorphisms in the cytokine genes and risk of hepatocellular carcinoma in low-risk non-Asians of USA.
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 gamma (IFNgamma), tumor necrosis factor-alpha (TNFalpha), 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 (IFNgamma, 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.
Ognjanovic
Simona
S
Department of Pediatrics, Division of Pediatric Epidemiology and Clinical Research, University of Minnesota, MMC 715, 420 Delaware Street S.E., Minneapolis, MN 55455, USA. ognja001@umn.edu
Yuan
Jian-Min
JM
Chaptman
Ann K
AK
Fan
Yunhua
Y
Yu
Mimi C
MC
D044383:Black People / Q000235:genetics; D006528:Carcinoma, Hepatocellular / Q000453:epidemiology / Q000235:genetics*; D016207:Cytokines / Q000235:genetics*; D048909:Diabetes Complications / Q000453:epidemiology; D003920:Diabetes Mellitus / Q000453:epidemiology; D005260:Female; D014644:Genetic Variation; D005838:Genotype; D006801:Humans; D007249:Inflammation / Q000453:epidemiology; D007371:Interferon-gamma / Q000235:genetics; D007378:Interleukins / Q000235:genetics; D008113:Liver Neoplasms / Q000453:epidemiology / Q000235:genetics*; D015141:Los Angeles / Q000453:epidemiology; D008297:Male; D011110:Polymorphism, Genetic; D044469:Racial Groups / Q000235:genetics; D012044:Regression Analysis; D012307:Risk Factors; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics; D014481:United States / Q000453:epidemiology; D044465:White People / Q000235:genetics; D001741:Black or African American
D016207:Cytokines; D007378:Interleukins; D014409:Tumor Necrosis Factor-alpha; D007371:Interferon-gamma