Background: Genetic variants of Patatin-like phospholipase domain-containing protein
3 (PNPLA3) and transmembrane 6 superfamily member 2 (TM6SF2) genes have been
reported with development of hepatocellular carcinoma (HCC). Aim: To explore the
role of The PNPLA3 rs738409 and TM6SF2 rs58542926 single nucleotide
polymorphisms (SNPs) on the incidence and survival of HCV induced HCC in
Method: This case-control study included (120) HCC and (144) Hepatitis
C virus (HCV) patients. Baseline clinical, laboratory, tumor characteristics data, HCC
recurrence, and overall survival were collected. PNPLA3 rs738409 and TM6SF2
rs58542926 polymorphism were detected by TaqMan allelic discrimination assay.
Results: HCC Patients were significantly older with male predominance. A significant
difference between TT genotype of TM6SF2 frequency was observed in HCC
compared with HCV patients. Moreover, T allele of TM6SF2 distributions revealed
significant contribution with different stages of HCC ( p =0.03). Both PNPLA3
rs738409 and TM6SF2 rs58542926 variants showed significant relation with treatment
response according to the modified RECIST criteria. Age and diabetes mellitus were
the independent factors associated with the development of HCC by multivariate
regression analysis. Diabetes, BCLC stage, performance status and response to
treatment were significantly associated with patients’ survival.
Conclusion : TM6SF2 rs58542926 polymorphism not PNPLA3 rs738409 could be implicated in the
development HCV induced HCC and its progression.