Genetic Polymorphisms of Cytochrome P4501A1 (CYP1A1) and Glutathione S-Transferase P1 (GSTP1) and Risk of Hepatocellular Carcinoma Among Chronic Hepatitis C Patients in Egypt

Abstract

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.

The Interaction of Smoking with Gene Polymorphisms on Four Digestive Cancers: A Systematic Review and Meta-Analysis

“…Among 12 studies on the GSTP1 polymorphism in Supplementary Table S1 , no significant correlations were found except one study on liver cancer in non-smokers (OR=7.364, 95% CI 1.671-32.440) 49 . There was no publication bias ( p >0.05).…”

“…Forty-three studies were performed in Asia, 11 studies were performed in Europe, 10 studies were performed in the Americas, and 3 studies were performed in Africa. Among all identified articles, 30 evaluated GSTM1 polymorphism 19 - 48 , 18 evaluated GSTT1 polymorphism 20 - 24 , 30 - 32 , 34 , 35 , 40 , 42 - 48 , 12 evaluated GSTP1 polymorphism 11 , 22 , 30 , 32 , 34 , 35 , 42 , 49 - 53 , 8 evaluated CYP1A1 IIe462Val polymorphism 9 , 27 , 28 , 54 - 58 , 7 evaluated CYP1A1 MspI polymorphism 26 , 28 , 45 , 54 , 57 , 58 , 8 evaluated NAT2 polymorphism 24 , 28 , 36 , 38 , 46 , 59 - 61 , 6 evaluated SULT1A1 polymorphism 24 , 45 , 62 - 65 , 8 evaluated hOGG1 polymorphism 66 - 73 , 7 evaluated XRCC1 polymorphism 52 , 67 , 69 , 74 - 77 , and 6 evaluated p53 polymorphism 78 - 83 .…”

Identification of potential core genes in hepatoblastoma via bioinformatics analysis

“…Similarly, pathway enrichment analyses were performed using the 497 down regulated genes to elucidate the action of hepatoblastoma. SNP in enriched genes such as ADH1B [Shih et al 2018], NAT2 [Farker et al 2003], CYP1A1 [Abo-Hashem et al 2016], CYP2D6 [Agundez et al 1996], GSTA1 [Akhdar et al 2016], MBL2 [Wang et al 2016] C6 [Wang et al 2016] and SERPINE1 [Divella et al 2015] were linked with advancement of hepatocellular carcinoma, but these polymorphic genes may be responsible for progression of hepatoblastoma. Enriched genes such as KMO (kynurenine 3-monooxygenase) [Jin et al 2015], HMGCS2 [Wang et al 2019], LIPG (lipase G, endothelial type) [Cadenas et al 2019], PON3 [Cai et al 2016], AASS (aminoadipate-semialdehyde synthase) [Xue et al 2019], PCK2 [Liu et al 2012], PPARGC1A [Wang et al 2018] and JUNB (JunB proto-oncogene, AP-1 transcription factor subunit) [Kim et al 2001] were associated with proliferation of hepatocellular carcinoma cells, but these genes may be associated with proliferation of hepatoblastoma cells.…”

CircRNA Cdr1as functions as a competitive endogenous RNA to promote hepatocellular carcinoma progression

“…Identifying prognostic biomarkers and treatment targets for HCC is of paramount importance. Some genes have already been identified to participate in the pathogenesis of HCC, including CYP1A1, p53, PTEN, ALDH2, EPHX1, etc [10–14]. Besides, some non-coding RNAs (ncRNAs) have also been proved to regulate the biological processes of HCC, including miRNA-302b, LncRNA DCST1-AS1 and circADAMTS13 [15–17].…”