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World J Gastroenterol. 2010 Nov 28;16(44):5635-41.

Genetic variations in the SMAD4 gene and gastric cancer susceptibility.

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  • 1Department of Molecular and Genetic Toxicology, School of Public Health, Cancer Center, Nanjing Medical University, 140 Hanzhong Road, Nanjing 210029, Jiangsu Province, China.



To explore the association between mothers against decapentaplegic homolog 4 (SMAD4) gene polymorphisms and gastric cancer risk.


Five tagging single nucleotide polymorphisms (tSNPs) in the SMAD4 gene were selected and genotyped in 322 gastric cancer cases and 351 cancer-free controls in a Chinese population by using the polymerase chain reaction restriction fragment length polymorphism method. Immunohistochemistry was used to examine SMAD4 protein expression in 10 normal gastric tissues adjacent to tumors.


In the single-locus analysis, two significantly decreased risk polymorphisms for gastric cancer were observed: the SNP3 rs17663887 TC genotype (adjusted odds ratio = 0.38, 95% confidence interval: 0.21-0.71), compared with the wild-type TT genotype and the SNP5 rs12456284 GG genotype (0.31, 0.16-0.60), and with the wild-type AA genotype. In the combined analyses of these two tSNPs, the combined genotypes with 2-3 protective alleles (SNP3 C and SNP5 G allele) had a significantly decreased risk of gastric cancer (0.28, 0.16-0.49) than those with 0-1 protective allele. Furthermore, individuals with 0-1 protective allele had significantly decreased SMAD4 protein expression levels in the normal tissues adjacent to tumors than those with 2-3 protective alleles (P = 0.025).


These results suggest that genetic variants in the SMAD4 gene play a protective role in gastric cancer in a Chinese population.

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