title: Single nucleotide polymorphism of rs430397 in the fifth intron of GRP78 gene and clinical relevance of primary hepatocellular carcinoma in Han Chinese: risk and prognosis.
abstract: Large number of data showed that allele variants in certain genes are markers for hepatocellular carcinoma (HCC). GRP78 is a stress-associated protein which is a central regulator of endoplasmic reticulum homeostasis due to its multiple functional roles in the folding, maturation and transport of proteins. A case-control study was conducted on 576 HCC patients, and 539 age- and gender-matched healthy subjects to examine whether rs430397 polymorphism in the fifth intron of GRP78 gene is associated with the development and prognosis of HCC. Polymorphism in rs430397 was analyzed by resequencing and TaqMan real-time PCR. Allele A, genotype AA and combined genotypes (AG+AA) displayed significantly increased risk for HCC (OR = 1.48, 95%CI = 1.07-1.79, p = 0.010; OR = 2.25, 95%CI = 1.08-3.38, p = 0.019; and OR = 1.50, 95%CI = 1.09-1.85, p = 0.012, respectively). Genotypes AA and AG were mainly associated with HBV-related HCC (85.8%; p < 0.00001 versus HBV noncarriers with HCC) and cirrhosis-related HCC (90%; p = 0.011 versus noncirrhosis HCC). Patients carrying the AA genotype had a shorter survival time (median 23.0 months in all cases; median 21.0 months in the cases carrying HBsAg). Like HBV and cirrhosis, the rs430397 is an independent prognostic factor influencing the survival of HCC. In conclusion, allele A and genotypes AA and AG of rs430397 may represent high risk and poor prognosis for HCC.
authors.affiliation: State Key Laboratory of Oncology in South China, Cancer Center, Sun Yat-sen University, Guangzhou, People's Republic of China.
authors.forename: Xiao
authors.initials: X
authors.lastname: Zhu
authors.forename: Min-Shan
authors.initials: MS
authors.lastname: Chen
authors.forename: Lin-Wei
authors.initials: LW
authors.lastname: Tian
authors.forename: Dong-Pei
authors.initials: DP
authors.lastname: Li
authors.forename: Pei-Lin
authors.initials: PL
authors.lastname: Xu
authors.forename: Marie C M
authors.initials: MC
authors.lastname: Lin
authors.forename: Dan
authors.initials: D
authors.lastname: Xie
authors.forename: Hsiang-Fu
authors.initials: HF
authors.lastname: Kung
mesh_terms: D000328:Adult; D000368:Aged; D044466:Asian People / Q000235:genetics*; D006528:Carcinoma, Hepatocellular / Q000150:complications / Q000235:genetics* / Q000821:virology; D016022:Case-Control Studies; D000091342:Endoplasmic Reticulum Chaperone BiP; D005260:Female; D005838:Genotype; D006360:Heat-Shock Proteins / Q000235:genetics*; D006509:Hepatitis B / Q000150:complications / Q000235:genetics; D006515:Hepatitis B virus / Q000502:physiology; D006801:Humans; D007438:Introns / Q000235:genetics*; D008113:Liver Neoplasms / Q000150:complications / Q000235:genetics* / Q000821:virology; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D011379:Prognosis; D012307:Risk Factors; D015996:Survival Rate
chemical_list: D000091342:Endoplasmic Reticulum Chaperone BiP; C000717247:HSPA5 protein, human; D006360:Heat-Shock Proteins