title: 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.
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: chi(2) = 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.
authors: Department of Epidemiology and Biostatistics, Cancer Research Center of Nanjing Medical University, Nanjing, China.
authors: Guangfu
authors: G
authors: Jin
authors: Ruifen
authors: R
authors: Miao
authors: Yimei
authors: Y
authors: Deng
authors: Zhibin
authors: Z
authors: Hu
authors: Yan
authors: Y
authors: Zhou
authors: Yongfei
authors: Y
authors: Tan
authors: Jianming
authors: J
authors: Wang
authors: Zhaolai
authors: Z
authors: Hua
authors: Weiliang
authors: W
authors: Ding
authors: Lina
authors: L
authors: Wang
authors: Wensen
authors: W
authors: Chen
authors: Jing
authors: J
authors: Shen
authors: Xinru
authors: X
authors: Wang
authors: Yaochu
authors: Y
authors: Xu
authors: Hongbing
authors: H
authors: Shen
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000428:Alcohol Drinking; D044466:Asian People; D016022:Case-Control Studies; D002681:China; D004815:Epidermal Growth Factor / Q000235:genetics*; D005260:Female; D005787:Gene Frequency; D005838:Genotype; D006239:Haplotypes; D006801:Humans; D008297:Male; D008875:Middle Aged; D011110:Polymorphism, Genetic; D011401:Promoter Regions, Genetic; D012044:Regression Analysis; D012307:Risk Factors; D012907:Smoking; D013274:Stomach Neoplasms / Q000235:genetics*
chemical_list: D004815:Epidermal Growth Factor