NOD1 and NOD2 Genetic Variants in Association with Risk of Gastric Cancer and Its Precursors in a Chinese Population.
BACKGROUND
Genetic variants of nucleotide-binding oligomerization domain-containing protein (NOD) may influence the outcome of Helicobacter pylori (H. pylori) infection and gastric carcinogenesis. To explore genetic variants of NOD1 and NOD2 in association with gastric cancer (GC) and its precursors, a population-based study was conducted in Linqu County, China.


METHODS
TagSNPs of NOD1 and NOD2 were genotyped by Sequenom MASS array in 132 GCs, and 1,198 subjects with precancerous gastric lesions, and were correlated with evolution of gastric lesions in 766 subjects with follow-up data.


RESULTS
Among seven tagSNPs, NOD1 rs2709800 and NOD2 rs718226 were associated with gastric lesions. NOD1 rs2709800 TG genotype carriers had a decreased risk of intestinal metaplasia (IM, OR: 0.53; 95% CI: 0.31-0.92), while NOD2 rs718226 G allele (AG/GG) showed increased risks of dysplasia (DYS, OR: 2.96; 95% CI: 1.86-4.71) and GC (OR: 2.35; 95% CI: 1.24-4.46). Moreover, an additive interaction between rs718226 and H. pylori was found in DYS or GC with synergy index of 3.08 (95% CI: 1.38-6.87) or 3.99 (95% CI: 1.55-10.22), respectively. The follow-up data indicated that NOD2 rs2111235 C allele (OR: 0.52; 95% CI: 0.32-0.83) and rs7205423 G allele (OR: 0.56; 95% CI: 0.35-0.89) were associated with decreased risk of progression in H. pylori-infected subjects.


CONCLUSIONS
NOD1 rs2709800, NOD2 rs718226, rs2111235, rs7205423 and interaction between rs718226 and H. pylori infection may be related to risk of gastric lesions.
Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Department of Cancer Epidemiology, Peking University Cancer Hospital & Institute, 52 Fu-cheng Road, Hai-dian District, Beijing 100142, China.
Zhe-Xuan
ZX
Li
Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Department of Cancer Epidemiology, Peking University Cancer Hospital & Institute, 52 Fu-cheng Road, Hai-dian District, Beijing 100142, China.
Yu-Mei
YM
Wang
Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Department of Cancer Epidemiology, Peking University Cancer Hospital & Institute, 52 Fu-cheng Road, Hai-dian District, Beijing 100142, China.
Fu-Bing
FB
Tang
Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Department of Cancer Epidemiology, Peking University Cancer Hospital & Institute, 52 Fu-cheng Road, Hai-dian District, Beijing 100142, China.
Lian
L
Zhang
Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Department of Cancer Epidemiology, Peking University Cancer Hospital & Institute, 52 Fu-cheng Road, Hai-dian District, Beijing 100142, China.
Yang
Y
Zhang
Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Department of Cancer Epidemiology, Peking University Cancer Hospital & Institute, 52 Fu-cheng Road, Hai-dian District, Beijing 100142, China.
Jun-Ling
JL
Ma
Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Department of Cancer Epidemiology, Peking University Cancer Hospital & Institute, 52 Fu-cheng Road, Hai-dian District, Beijing 100142, China.
Tong
T
Zhou
Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Department of Cancer Epidemiology, Peking University Cancer Hospital & Institute, 52 Fu-cheng Road, Hai-dian District, Beijing 100142, China.
Wei-Cheng
WC
You
Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Department of Cancer Epidemiology, Peking University Cancer Hospital & Institute, 52 Fu-cheng Road, Hai-dian District, Beijing 100142, China.
Kai-Feng
KF
Pan
D044466:Asian People / Q000235:genetics*; D018450:Disease Progression; D005260:Female; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease; D016481:Helicobacter Infections / Q000150:complications; D006801:Humans; D008297:Male; D008875:Middle Aged; D053474:Nod1 Signaling Adaptor Protein / Q000235:genetics*; D053473:Nod2 Signaling Adaptor Protein / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D011230:Precancerous Conditions / Q000235:genetics* / Q000473:pathology; D012307:Risk Factors; D013274:Stomach Neoplasms / Q000235:genetics* / Q000382:microbiology
C119067:NOD1 protein, human; C429018:NOD2 protein, human; D053474:Nod1 Signaling Adaptor Protein; D053473:Nod2 Signaling Adaptor Protein