Genetic Polymorphisms of Cytochrome P4501A1 (CYP1A1) and Glutathione S-Transferase P1 (GSTP1) and Risk of Hepatocellular Carcinoma Among Chronic Hepatitis C Patients in Egypt.
Cytochrome P450 1A1 (CYP1A1) and Glutathione S-transferase P1 (GSTP1) genes are involved in the metabolism of many carcinogens. Polymorphisms in these genes with altered enzyme activity have been reported. The present study evaluated the synergistic effect between CYP1A1 and GSTP1 gene polymorphisms and smoking on development of HCV-related liver disease and hepatocellular carcinoma (HCC). The patients group comprised 40 patients with HCC and 40 patients with liver cirrhosis. The control group comprised 40 healthy subjects having no history of malignancy. The genetic polymorphisms were studied using polymerase chain reaction restriction fragment length polymorphism (PCR RFLP) technique on blood samples. The number of current or former smoker among HCC and cirrhotic patients as well as the median Pack/year of cigarette smoked were significantly higher in HCC and liver cirrhotic patients than in control group. Subjects with CYP1A1 gene variants (m1 and m3) had no significant risk to develop cirrhosis or HCC compared to control group. Individuals carrying the Ile/Val genotype of GSTP1 had a significant increased risk of HCC (OR of 2.2, 95 % CI 1.143-4.261) and had larger tumor size. No significant risk was observed on combining both genes variants or on combining smoking with variants of both genes. In conclusion, the GSTP1 Ile/Val genotype and Val allele are associated with an increased risk of HCC. CYP1A1 and GSTP1 genes variants interaction did not increase the risk of HCC.
Department of Clinical Pathology, Faculty of Medicine, Mansoura University, Mansoura, 35516, Egypt.
Ekbal M
EM
Abo-Hashem
Department of Clinical Pathology, Faculty of Medicine, Mansoura University, Mansoura, 35516, Egypt. dr.wafaelemshaty@yahoo.com.
Wafaa M
WM
El-Emshaty
Department of Tropical Medicine, Mansoura University, Mansoura, Egypt.
Raghda El Sayed
Rel S
Farag
Department of Tropical Medicine, Mansoura University, Mansoura, Egypt.
Sahar
S
Zakaria
Department of Tropical Medicine, Mansoura University, Mansoura, Egypt.
Mohammed
M
Abd El-Aziz
Department of Clinical Pathology, Mansoura New General Hospital, Mansoura, Egypt.
Azza
A
Ghonaim
D006528:Carcinoma, Hepatocellular / Q000235:genetics*; D019363:Cytochrome P-450 CYP1A1 / Q000235:genetics*; D004534:Egypt; D005260:Female; D020022:Genetic Predisposition to Disease; D051549:Glutathione S-Transferase pi / Q000235:genetics*; D019698:Hepatitis C, Chronic / Q000235:genetics*; D006801:Humans; D008113:Liver Neoplasms / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D012907:Smoking / Q000009:adverse effects
C569463:CYP1A1 protein, human; D019363:Cytochrome P-450 CYP1A1; C496556:GSTP1 protein, human; D051549:Glutathione S-Transferase pi
CYP1A1; GSTP1; HCC; HCV; Smoking