J Liver Cancer.  2019 Mar;19(1):46-54. 10.17998/jlc.19.1.46.

Effect of PTEN Polymorphism on the Development of Hepatitis B Virus-associated Hepatocellular Carcinoma

• Kim SS
• Eun JW
• Cho HJ
• Lee HY
• Seo CW
• Lee GH
• Yoon SY
• Noh CK
• Cho SW
• Cheong JY

• KMID: 2448276
• DOI: http://doi.org/10.17998/jlc.19.1.46

Abstract

BACKGROUND/AIMS
Phosphatase and tensin homolog (PTEN) is a known tumor suppressor gene that is downregulated in hepatocellular carcinoma (HCC). Here, we investigated the association between single nucleotide polymorphisms (SNPs) of PTEN and HCC development in patients with hepatitis B virus (HBV) infection.
METHODS
Six SNPs of PTEN at positions rs1234221, rs1903860, rs1234220, rs1903858, rs2299941, and rs17431184 were analyzed in a development population (417 chronic HBV carriers without HCC and 281 chronic HBV carriers with HCC). PTEN rs1903858, rs1903860, and rs2299941 SNPs were further assessed for the development of HCC in a validation population of 200 patients with HBV-related liver cirrhosis.
RESULTS
In the development population, PTEN rs1903860 C allele, rs1903858 G allele, and rs2299941 G allele were associated with a low risk of HCC. The haplotype A-T-A-A-A was associated with an increased risk of HCC (recessive model; odds ratio=2.277, 95% confidence interval [CI] =1.144-4.532, P=0.019). In the validation population, PTEN rs2299941 G allele was the only significant protective genetic polymorphism related to HCC development after adjustment for age and sex (hazard ratio=0.582, 95% CI =0.353-0.962, P=0.035).
CONCLUSIONS
These findings suggest that genetic polymorphisms in PTEN may affect HCC development in patients with chronic HBV infection.

Keyword

PTEN; Polymorphism, single nucleotide; Hepatocellular carcinoma; Hepatitis B virus

MeSH Terms

Alleles
Carcinoma, Hepatocellular*
Genes, Tumor Suppressor
Haplotypes
Hepatitis B virus
Hepatitis B*
Hepatitis*
Humans
Liver Cirrhosis
Polymorphism, Genetic
Polymorphism, Single Nucleotide

Figure

• 

  Figure 1. Linkage disequilibrium blocks and haplotypes of PTEN. (A) Haplotypes of rs1234221, rs1903860, rs1234220, rs1903858, and rs2299941 in PTEN and linkage disequilibrium coefficient (D' and r2 ). (B) Haplotypes of rs1903860, rs1903858, and rs2299941 in PTEN and linkage disequilibrium coefficient (D' and r2 ). PTEN, phosphatase and tensin homolog.

• 

  Figure 2. Kaplan-Meier curves of cumulative probabilities of HCC development in the validation population according to (A) PTEN rs2299941 genotype and (B) haplotype TGA carrier. HCC , hepatocellular carcinoma; PTEN, phosphatase and tensin homolog.

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