IngentaConnect Variant genotypes and haplotypes of the epidermal growth factor g...

Authors: Jin, Guangfu; Miao, Ruifen¹; Deng, Yimei¹; Hu, Zhibin¹; Zhou, Yan²; Tan, Yongfei²; Wang, Jianming³; Hua, Zhaolai³; Ding, Weiliang²; Wang, Lina¹; Chen, Wensen¹; Shen, Jing¹; Wang, Xinru⁴; Xu, Yaochu¹; Shen, Hongbing

Source: Cancer Science, Volume 98, Number 6, June 2007 , pp. 864-868(5)

Publisher: Blackwell Publishing

Abstract:

Epidermal growth factor (EGF), a ligand of the EGF receptor, plays a critical role in the development of gastric cancer. Genetic variants in its promoter region may influence transcription activity and contribute to gastric cancer predisposition. To test this hypothesis, we genotyped three EGF promoter polymorphisms (G61A, G-1380A, and A-1744G) in a case-control study of 675 gastric cancer cases and 704 cancer-free controls. We found that the variant genotypes of EGF 61GA/AA were associated with a significantly decreased risk of gastric cancer (OR = 0.77, 95% CI = 0.61-0.95), when compared with wild-type homozygote 61GG. In the combined analysis with all three loci of EGF, subjects carrying one or more variant loci had a significantly decreased risk of gastric cancer in a dose-response manner (adjusted OR = 0.58, 95% CI = 0.42-0.80 for subjects carrying one variant locus and OR = 0.46, 95% CI = 0.32-0.66 for those carrying two to three variant loci, respectively; trend test: χ² = 16.14, P < 0.001). Compared with the most common haplotype GGA, haplotypes AGA, GGG and GAA (each containing one variant allele) were associated with 33%, 29% and 34% significantly decreased risk of gastric cancer (adjusted OR = 0.67, 95% CI = 0.55-0.82 for AGA; OR = 0.71, 95% CI = 0.57-0.88 for GGG and OR = 0.66, 95% CI = 0.52-0.84 for GAA, respectively). Our findings indicate that variant genotypes and haplotypes of EGF promoter might play a role in gastric carcinogenesis. (Cancer Sci 2007; 98: 864-868)

Document Type: Research article

DOI: 10.1111/j.1349-7006.2007.00463.x

Affiliations: 1: Department of Epidemiology and Biostatistics, Cancer Research Center of Nanjing Medical University, Nanjing 210029; 2: Yixing People's Hospital, Yixing City 214200, Jiangsu Province; and 3: Yangzhong Cancer Institute, Yangzhong City 212200, Jiangsu Province, China 4: Laboratory of Toxicology, Nanjing Medical University School of Public Health, Nanjing 210029;

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Variant genotypes and haplotypes of the epidermal growth factor gene promoter are associated with a decreased risk of gastric cancer in a high-risk Chinese population