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Genetic variations in the SMAD4 gene and gastric cancer susceptibility
Dong-Mei Wu, Hai-Xia Zhu, Qing-Hong Zhao, Zhi-Zhong Zhang, Shi-Zhi Wang, Mei-Lin Wang, Wei-Da Gong, Ming Tan, Zheng-Dong Zhang
Dong-Mei Wu, Zhi-Zhong Zhang, Shi-Zhi Wang, Mei-Lin Wang, Zheng-Dong Zhang, Department of Molecular and Genetic Toxicology, School of Public Health, Cancer Center, Nanjing Medical University, Nanjing 210029, Jiangsu Province, China
Hai-Xia Zhu, Core laboratory, Nantong Tumor Hospital, Nantong 226001, Jiangsu Province, China
Qing-Hong Zhao, Department of General Surgery, The Second Affiliated Hospital of Nanjing Medical University, Nanjing 210029, Jiangsu Province, China
Wei-Da Gong, Department of Surgery, Yixing People’s Hospital, Yixing 214200, Jiangsu Province, China
Ming Tan, Department of General Surgery, Institute of Cancer Research, Yangzhong People’s Hospital, Yangzhong 212200, Jiangsu Province, China
Author contributions: Wu DM, Zhu HX and Zhao QH contributed equally to this work; Wu DM, Zhu HX and Zhang ZD designed the research; Zhu HX performed the majority of the experiments; Zhao QH, Gong WD and Tan M coordinated the collection of the human samples; Wu DM analyzed the data and wrote the manuscript; Zhang ZZ, Wang ML and Wang SZ were involved in editing the manuscript.
Supported by The National Natural Science Foundation of China, No. 30800926, No. 30872084, No. 81001274, and No. 30972444; and the Natural Science Foundation of Jiangsu Province, No. BK2010080
Correspondence to: Zheng-Dong Zhang, Professor, Department of Molecular and Genetic Toxicology, School of Public Health, Cancer Center, Nanjing Medical University, 140 Hanzhong Road, Nanjing 210029, Jiangsu Province, China. drzdzhang@gmail.com
Telephone: +86-25-86862937 Fax: +86-25-86527613
Received: May 24, 2010
Revised: August 26, 2010
Accepted: September 3, 2010
Published online: November 28, 2010
AIM: To explore the association between mothers against decapentaplegic homolog 4 (SMAD4) gene polymorphisms and gastric cancer risk.
METHODS: 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 reactionrestriction fragment length polymorphism method. Immunohistochemistry was used to examine SMAD4 protein expression in 10 normal gastric tissues adjacent to tumors.
RESULTS: 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).
CONCLUSION: These results suggest that genetic variants in the SMAD4 gene play a protective role in gastric cancer in a Chinese population.
