Objective: To elucidate the association of genetic polymorphisms of key molecules in JAK/STAT signaling pathway with susceptibility of hepatocellular carcinoma (HCC).
Methods: A total of 367 HCC patients and 367 healthy controls were recruited in this sex- and age-matched case-control study. Genetic polymorphisms of IL-6 (rs1800796, -572C > G), STAT3 (rs744166, +26312T > C; rs3816769, +42240T > C; rs6503695, +40980T > C), EGFR (rs11543848, +142530A > G), and mTOR (rs7211818, +170278A > G; rs9674559, +196983A > G; rs11653499, +65678G > A) were genotyped using a mass spectrometry method. Odds ratio (OR) and 95% confidence interval (CI) were calculated.
Results: Genotype frequency of the 8 polymorphisms of IL-6, STAT3, EGFR, and mTOR were not significantly different between the patients with HCC and the controls. When stratified by sex, the female subjects who carried STAT3 +26312CC, +42240CC, or +40980CC had a decreased risk of HCC when compared to those who carried TT allele (OR = 0.192, 95%CI: 0.047 - 0.784; OR = 0.180, 95%CI: 0.045 - 0.725; OR = 0.198, 95%CI: 0.049 - 0.806, respectively). When compared with AA genotype on the site of EGFR +142530, the (AG + GG) genotype reduced the risk of HCC in women (OR = 0.422, 95%CI: 0.179 - 0.994).
Conclusion: The polymorphisms of IL-6 (rs1800796) and mTOR (rs7211818, rs9674559, and rs11653499) were not associated with the HCC susceptibility. Those carrying CC allele in three loci (rs744166, rs3816769, and rs6503695) of STAT3 and (AG + GG) in rs11543848 of EGFR had a decreased risk of HCC in women. However, these results need to be validated using larger sample size.