Genetic polymorphisms of epidermal growth factor in relation to risk of hepatocellular carcinoma: two case-control studies
1 Division of Cancer Control and Population Sciences, University of Pittsburgh Cancer Institute, UPMC Cancer Pavilion, Suite 4C, 5150 Centre Avenue, Pittsburgh, PA, 15232, USA
2 Department of Epidemiology, University of Pittsburgh Graduate School of Public Health, A529 Crabtree Hall, 130 DeSoto Street, Pittsburgh, PA, 15261, USA
3 Masonic Cancer Center, University of Minnesota, 554 CCRB, 425 East River Road, Minneapolis, MN, 55455, USA
4 Masonic Cancer Center, University of Minnesota, 1-185 Moos Tower, 515 Delaware Street SE, Minneapolis, MN, 55455, USA
5 The USC/Norris Comprehensive Cancer Center, Keck School of Medicine, University of Southern California, 1441 Eastlake Avenue, Los Angeles, CA, 90089, USA
6 Department of Pathology, Rancho Los Amingo Medical Center, 7601 E. Imperial Highway, JPI Building Basement, Downey, CA, 90242, USA
BMC Gastroenterology 2013, 13:32 doi:10.1186/1471-230X-13-32Published: 18 February 2013
Earlier, we reported a highly statistically significant association between T-helper 1 (Th1) and Th2 cytokine genotypes and hepatocellular carcinoma (HCC) risk among natives of southern Guangxi, China, a hyperendemic region for HCC. Epidermal growth factor (EGF) plays a critical role in malignant transformation of hepatocytes and tumor progression. A polymorphism in the EGF gene (61A > G) results in elevation of EGF in liver tissues and blood. Epidemiological data are sparse on the possible association between EGF genetic polymorphism and HCC risk.
The EGF 61A > G polymorphism, multiple Th1 and Th2 genotypes, and environmental risk factors for HCC were determined on 117 HCC cases and 225 healthy control subjects among non-Asians of Los Angeles County, California, a low-risk population for HCC, and 250 HCC cases and 245 controls of southern Guangxi, China.
Following adjustment for all known or suspected HCC risk factors, non-Asians in Los Angeles who possessed at least one copy of the high activity 61*G allele of the EGF gene showed a statistically non-significant, 78% increased risk of HCC compared with those possessing the EGF A/A genotype. This EGF-HCC risk association significantly strengthened among heavy users of alcohol [odds ratio (OR) = 3.44, 95% confidence interval (CI) = 0.93–12.76, P = 0.065)], and among individuals carrying the high-risk Th1/Th2 genotypes for HCC (OR = 3.34, 95% CI = 1.24-9.03, P = 0.017). No association between EGF genotype and HCC risk was observed among Chinese in southern Guangxi, China.
Genetic polymorphism in the EGF gene resulting in elevated level of EGF, may contribute to HCC risk among low-risk non-Asians in Los Angeles.