Chitinase 3‐like‐1, Tolloid‐like protein 1, and intergenic gene polymorphisms are predictors for hepatocellular carcinoma development after hepatitis C virus eradication by direct‐acting antivirals

Abstract

Hepatocellular carcinoma (HCC) is a major cause of cancer death in Egypt. There is still a risk for HCC development even after eradicating hepatitis C virus (HCV) by direct-acting antivirals (DAAs). Chitinase-3-like-protein-1 (CHI3L1), a biomarker for predicting many diseases, plays an essential role in inflammation, angiogenesis, and antiapoptosis. Tolloid-like protein 1 (TLL1) may be involved in hepatic fibrogenesis and carcinogenesis. This study aimed to determine the role and combined effect of CHI3L1 (rs880633), TLL1 (rs1503298), and an intergenic (rs597533) polymorphisms on the risk of developing HCC in Egyptian patients after achieving sustained virological response (SVR) by DAAs. Blood samples were collected from 68 HCC patients, 77 non-HCC subjects, and 80 healthy controls. The DNA was extracted and analyzed for rs880633, rs1503298, and rs597533 using Genotyping TaqMan™ assay. The result of the present study showed a significant difference in genotypes and alleles frequencies in both (rs880633) and (rs597533) in HCC group as compared to healthy control and also as compared to the non-HCC group. However, regarding to (rs1503298) genotypes and alleles between the HCC and non-HCC groups, there were no significant differences. Combined polymorphism in more than one gene simultaneously showed a higher risk to HCC after SVR than an individual locus. Both allelic and genotypic variations of the CHI3L1 gene (rs880633) and an intergenic (rs597533) seemed to be significant predictors confirming a great risk for HCC susceptibility in Egyptian patients achieved SVR. Patients with a polymorphism in more than one gene showed an increased risk to HCC after SVR rather than individual locus.

Functional variants of the chitinase 3‐like 1 gene are associated with clinicopathologic outcomes and progression of prostate cancer

“…They were associated with influencing the occurrence, severity, or progression of different cancer types. Additionally, these genetic variants were linked to modulation of the expression of the CHI3L1 gene 19–22 . The allelic discrimination of these four CHI3L1 SNPs including rs4950928 (assay ID: C_27832042_10), rs6691378 (assay ID: C_29933614_10), rs880633 (assay ID: C_11891591_1) and rs10399805 (assay ID: C_29969647_10) was evaluated by utilizing the TaqMan SNP Genotyping Assay.…”

“…Additionally, these genetic variants were linked to modulation of the expression of the CHI3L1 gene. 19 , 20 , 21 , 22 The allelic discrimination of these four CHI3L1 SNPs including rs4950928 (assay ID: C_27832042_10), rs6691378 (assay ID: C_29933614_10), rs880633 (assay ID: C_11891591_1) and rs10399805 (assay ID: C_29969647_10) was evaluated by utilizing the TaqMan SNP Genotyping Assay. This analysis was conducted using the ABI StepOnePlus™ Real‐Time PCR System, a product of Thermo Fisher Scientific.…”

“…Therefore, the CHI3L1 rs4950928 C allele was reported to be associated with risk of rectal cancer and increased serum levels of CHI3L1 in Egyptians 19 . Moreover, the CHI3L1 rs880633 C allele was also correlated with the risk of liver cancer and higher serum CHI3L1 levels compared with the rs880633 T allele 20 . Furthermore, Su et al.…”

“…19 Moreover, the CHI3L1 rs880633 C allele was also correlated with the risk of liver cancer and higher serum CHI3L1 levels compared with the rs880633 T allele. 20…”

“… 19 Moreover, the CHI3L1 rs880633 C allele was also correlated with the risk of liver cancer and higher serum CHI3L1 levels compared with the rs880633 T allele. 20 Furthermore, Su et al. indicated a significant association of the homozygous phenotype (AA) for the minor allele of CHI3L1 rs10399805 and rs6691378 with a lower risk of developing lymph node (LN) metastasis in Taiwanese with oral cancer.…”