An insertion/deletion polymorphism within RERT-lncRNA modulates hepatocellular carcinoma risk

Area of Science:

• Genetics
• Oncology
• Molecular Biology

Background:

• Prolyl hydroxylase 1 (EGLN2) regulates hypoxia-inducible factor degradation, influencing tumorigenesis.
• Polymorphisms in EGLN2 may affect cancer cell survival and susceptibility, especially under hypoxic conditions.

Purpose of the Study:

• To investigate the association between the EGLN2 promoter polymorphism rs10680577 and hepatocellular carcinoma (HCC) risk in Chinese populations.
• To explore the functional impact of rs10680577 on EGLN2 and RERT-lncRNA expression and its potential role in hepatocarcinogenesis.

Main Methods:

• Case-control studies involving 623 HCC cases and 1,242 controls, with replication in an independent cohort (444 cases, 450 controls).
• Logistic regression analysis to assess the association between rs10680577 and HCC risk.
• Genotype-phenotype correlation studies (in vivo and in vitro) and in silico prediction to evaluate the functional effects of the polymorphism.

Main Results:

• The deletion allele of rs10680577 was significantly associated with increased HCC risk in both study cohorts (OR = 1.40-1.49).
• The association was stronger in current smokers compared to nonsmokers.
• The deletion allele correlated with higher EGLN2 and RERT-lncRNA expression, and in silico analysis suggested the insertion allele might disrupt RERT-lncRNA structure.

Conclusions:

• The rs10680577 polymorphism in EGLN2 contributes to hepatocarcinogenesis, likely by affecting RERT-lncRNA structure and subsequently EGLN2 expression.
• This polymorphism represents a potential biomarker for the early diagnosis of HCC.