Polymorphism of DNA Methyltransferase 3b and Association with Development and Prognosis in Gastric Cancer.
OBJECTIVE
DNA methyltransferase 3b (DNMT3b) plays an important role in abnormal methylation during tumorigenesis. Polymorphism of the DNMT3b gene may influence DNMT3b activity and be associated with cancer risk. This study aimed to investigate the association between single nucleotide polymorphisms (SNPs) of the DNMT3b gene and susceptibility and prognosis of gastric cancer.


METHODS
Four hundred and forty-seven histologically-confirmed gastric cancer cases, 111 gastric atrophy cases and 961 tumor-free controls were enrolled into the study. Five tag SNPs (rs6119954, rs1569686, rs4911107, rs4911259 and rs8118663) of the DNMT3b gene were genotyped by TaqMan assay. DNMT3b expression was evaluated in 104 cancer tissues by immunohistochemistry method.


RESULTS
The median follow-up time for 422 gastric patients with prognosis information was 55.1 (51.8-58.5) month. We found that individuals with the rs1569686 variant genotype (TG/GG) were significantly associated with poor prognosis in gastric cancer compared to those carrying the TT genotype (HR = 1.43, 95%CI: 1.02-1.99). This trend was more evident in the long-term survival of gastric cancer. Similar results were observed for the G allele carriers of rs4911107 and T allele carriers of rs4911259 as these two sites were in complete linkage disequilibrium with rs1569686. The rs8118663 GG carriers tended to live shorter than AA/AG genotype (HR = 2.72, 95%CI: 1.45-5.12) in patients living longer than 2.0 years. None of the five SNPs was associated with the risks of gastric cancer or gastric atrophy. And no relationship was found between each of the five SNPs and DNMT3b expression.


CONCLUSIONS
This study provides evidence that DNMT3b polymorphisms may predict long-term survival of gastric cancer. However, further studies are needed to reveal the underlying biological roles of DNMT3b polymorphism.
Division of Clinical Epidemiology, First Hospital of Jilin University, Changchun, Jilin, 130021, China.
Chuan
C
Wang
Division of Clinical Epidemiology, First Hospital of Jilin University, Changchun, Jilin, 130021, China.
Zhifang
Z
Jia
Division of Clinical Epidemiology, First Hospital of Jilin University, Changchun, Jilin, 130021, China.
Donghui
D
Cao
Division of Clinical Epidemiology, First Hospital of Jilin University, Changchun, Jilin, 130021, China.
Lili
L
You
Division of Pathology, First Hospital of Jilin University, Changchun, Jilin, 130021, China.
Meishan
M
Jin
Division of Clinical Epidemiology, First Hospital of Jilin University, Changchun, Jilin, 130021, China.
Xing
X
Wu
Division of Clinical Epidemiology, First Hospital of Jilin University, Changchun, Jilin, 130021, China.
Simin
S
Wen
Department of Gastric and Colorectal Surgery, First Hospital of Jilin University, Changchun, Jilin, 130021, China.
Xueyuan
X
Cao
Division of Clinical Epidemiology, First Hospital of Jilin University, Changchun, Jilin, 130021, China.
Jing
J
Jiang
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000483:Alleles; D016022:Case-Control Studies; D004248:DNA (Cytosine-5-)-Methyltransferases / Q000235:genetics*; D005260:Female; D005500:Follow-Up Studies; D005757:Gastritis, Atrophic / Q000235:genetics; D015870:Gene Expression; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D060787:Neoplasm Grading; D009367:Neoplasm Staging; D020641:Polymorphism, Single Nucleotide; D011379:Prognosis; D013274:Stomach Neoplasms / Q000188:drug therapy / Q000235:genetics* / Q000401:mortality* / Q000473:pathology; D047368:Tumor Burden; D000097584:DNA Methyltransferase 3B
D004248:DNA (Cytosine-5-)-Methyltransferases; D000097584:DNA Methyltransferase 3B