Heat shock protein A1B 1267 polymorphism is highly associated with risk and prognosis of hepatocellular carcinoma: a case-control study.
We conducted a case-control study to elucidate the role of heat shock protein A1B (HSPA1B) 1267 single nucleotide polymorphism (SNP) on the risk and prognosis of hepatocellular carcinoma (HCC). Subjects enrolled included 150 pairs of sex- and age-matched HCC patients and unrelated controls. Genomic DNA was typed for HSPA1B1267 SNP using polymerase chain reaction with restriction fragment length polymorphism. The frequencies of the HSPA1B P2/P2 genotype and the HSPA1B P2 allele in HCC patients were higher than in unrelated controls (each p = 0.0001). Multivariate analysis identified the following independent risk factors for HCC: HSPA1B P1/P2 genotype (odds ratio [OR], 2.34; 95% confidence interval [CI], 1.07-5.11), HSPA1B P2/P2 genotype (OR, 12.06; 95% CI, 4.43-32.79), hepatitis B surface antigen (HBsAg) (OR, 25.95; 95% CI, 11.88-56.68), and antibodies to hepatitis C virus (anti-HCV) (OR, 70.43; 95% CI, 21.89-226.64). There was an additive interaction between HSPA1B P2 allele carriers and the presence of either HBsAg (synergy index = 2.48) or anti-HCV (synergy index = 1.52). However, as HSPA1B1267 SNP is a silent mutation, it is a surrogate genetic marker for increasing risk of HCC. Our findings indicate that patients with chronic hepatitis B/hepatitis C virus infection who harbor this SNP represent a high-risk group for HCC. They should receive more intensive surveillance for early detection of HCC. Moreover, patients with the HSPA1B P2 allele had significantly longer survival (p = 0.002).The limitations of this study include the unknown functional significance of the HSPA1B1267 polymorphism, the relatively small sample size, the fact that this was not a prospective study of cases and controls, and the questionable generalizability of the findings given the specific ethnic composition of the population studied.
Jeng
Jen-Eing
JE
From Department of Clinical Laboratory (JEJ, JGC) and Internal Medicine (JFT, ZYL, MYH, SCC, WLC, LYW, MLY, CYD), and Department of Clinical Laboratory, Internal Medicine, and Biochemistry (LYC), Faculty of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan; and the Institute of Biomedical Sciences (MSH), Academia Sinica, Taipei, Taiwan.
Tsai
Jung-Fa
JF
Chuang
Lea-Yea
LY
Ho
Mei-Shang
MS
Lin
Zu-Yau
ZY
Hsieh
Min-Yuh
MY
Chen
Shin-Chern
SC
Chuang
Wan-Lung
WL
Wang
Liang-Yen
LY
Yu
Ming-Lung
ML
Dai
Chia-Yen
CY
Chang
Jan-Gowth
JG
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000483:Alleles; D006528:Carcinoma, Hepatocellular / Q000209:etiology*; D016022:Case-Control Studies; D004247:DNA / Q000032:analysis; D042241:Early Diagnosis; D005260:Female; D005787:Gene Frequency; D005819:Genetic Markers / Q000235:genetics; D005838:Genotype; D018840:HSP70 Heat-Shock Proteins / Q000235:genetics*; D006514:Hepatitis B Surface Antigens / Q000032:analysis; D019694:Hepatitis B, Chronic / Q000150:complications; D018937:Hepatitis C Antibodies / Q000032:analysis; D019698:Hepatitis C, Chronic / Q000150:complications; D006801:Humans; D008113:Liver Neoplasms / Q000209:etiology*; D008297:Male; D008875:Middle Aged; D009154:Mutation / Q000235:genetics; D016133:Polymerase Chain Reaction; D012150:Polymorphism, Restriction Fragment Length; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D011379:Prognosis; D012307:Risk Factors
D005819:Genetic Markers; D018840:HSP70 Heat-Shock Proteins; C525621:HSPA1B protein, human; D006514:Hepatitis B Surface Antigens; D018937:Hepatitis C Antibodies; D004247:DNA