title: A Functional Polymorphism (rs2494752) in the AKT1 Promoter Region and Gastric Adenocarcinoma Risk in an Eastern Chinese Population.
abstract: AKT is an important signal transduction protein that plays a crucial role in cancer development. Therefore, we evaluated associations between single nucleotide polymorphisms (SNPs) in the AKT promoter region and gastric cancer (GCa) risk in a case-control study of 1,110 GCa patients and 1,114 matched cancer-free controls. We genotyped five SNPs (AKT1 rs2494750G >C, AKT1 rs2494752A >G, AKT1 rs10138227C >T, AKT2 rs7254617G>A and AKT2 rs2304186G >T) located in the 5' upstream regulatory, first intron or promoter regions. In the logistic regression analysis, a significantly elevated GCa risk was associated with the rs2494752 AG/GG variant genotypes (adjusted odds ratio [OR] = 1.20, 95% confidence interval [CI] = 1.02-1.42) under a dominant genetic model, and this risk was more evident in subgroups of ever drinkers. The luciferase reporter assay showed that the rs2494752 G allele significantly increased luciferase activity. Our results suggest that the potentially functional AKT1 rs2494752 SNP may affect GCa susceptibility, likely by modulating the AKT1 promoter transcriptional activity. Larger, independent studies are warranted to validate our findings.
authors.affiliation: Cancer Institute, Collaborative Innovation Center for Cancer Medicine, Fudan University Shanghai Cancer Center, Shanghai 200032, China.|Department of Oncology, Shanghai Medical College, Fudan University, Shanghai 200032, China.
authors.forename: Meng-Yun
authors.initials: MY
authors.lastname: Wang
authors.affiliation: Cancer Institute, Collaborative Innovation Center for Cancer Medicine, Fudan University Shanghai Cancer Center, Shanghai 200032, China.|Department of Pediatric Surgery, Guangzhou Women and Children's Medical Center, Guangzhou Medical University, Guangzhou 510623, Guangdong, China.
authors.forename: Jing
authors.initials: J
authors.lastname: He
authors.affiliation: Cancer Institute, Collaborative Innovation Center for Cancer Medicine, Fudan University Shanghai Cancer Center, Shanghai 200032, China.|Department of Oncology, Xin Hua Hospital Affiliated To Shanghai Jiao Tong University School of Medicine, Shanghai 200092, China.
authors.forename: Mei-Ling
authors.initials: ML
authors.lastname: Zhu
authors.affiliation: Cancer Institute, Collaborative Innovation Center for Cancer Medicine, Fudan University Shanghai Cancer Center, Shanghai 200032, China.|Department of Oncology, Shanghai Medical College, Fudan University, Shanghai 200032, China.
authors.forename: Xiao-Yan
authors.initials: XY
authors.lastname: Teng
authors.affiliation: Cancer Institute, Collaborative Innovation Center for Cancer Medicine, Fudan University Shanghai Cancer Center, Shanghai 200032, China.|Department of Oncology, Shanghai Medical College, Fudan University, Shanghai 200032, China.
authors.forename: Qiao-Xin
authors.initials: QX
authors.lastname: Li
authors.affiliation: Department of Pathology, Fudan University Shanghai Cancer Center, Shanghai 200032, China.
authors.forename: Meng-Hong
authors.initials: MH
authors.lastname: Sun
authors.affiliation: Ministry of Education Key Laboratory of Contemporary Anthropology, State Key Laboratory of Genetic Engineering, School of Life Sciences, Fudan University, Shanghai 200433, China.|Fudan-Taizhou Institute of Health Sciences, Taizhou 225300, Jiangsu, China.
authors.forename: Xiao-Feng
authors.initials: XF
authors.lastname: Wang
authors.affiliation: Ministry of Education Key Laboratory of Contemporary Anthropology, State Key Laboratory of Genetic Engineering, School of Life Sciences, Fudan University, Shanghai 200433, China.|Fudan-Taizhou Institute of Health Sciences, Taizhou 225300, Jiangsu, China.
authors.forename: Ya-Jun
authors.initials: YJ
authors.lastname: Yang
authors.affiliation: Ministry of Education Key Laboratory of Contemporary Anthropology, State Key Laboratory of Genetic Engineering, School of Life Sciences, Fudan University, Shanghai 200433, China.|Fudan-Taizhou Institute of Health Sciences, Taizhou 225300, Jiangsu, China.
authors.forename: Jiu-Cun
authors.initials: JC
authors.lastname: Wang
authors.affiliation: Ministry of Education Key Laboratory of Contemporary Anthropology, State Key Laboratory of Genetic Engineering, School of Life Sciences, Fudan University, Shanghai 200433, China.|Fudan-Taizhou Institute of Health Sciences, Taizhou 225300, Jiangsu, China.
authors.forename: Li
authors.initials: L
authors.lastname: Jin
authors.affiliation: Department of Abdominal Surgery, Fudan University Shanghai Cancer Center, Shanghai 200032, China.
authors.forename: Ya-Nong
authors.initials: YN
authors.lastname: Wang
authors.affiliation: Cancer Institute, Collaborative Innovation Center for Cancer Medicine, Fudan University Shanghai Cancer Center, Shanghai 200032, China.|Duke Cancer Institute, Duke University Medical Center, Durham, NC 27710, USA.
authors.forename: Qing-Yi
authors.initials: QY
authors.lastname: Wei
mesh_terms: D000230:Adenocarcinoma / Q000235:genetics* / Q000473:pathology; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000483:Alleles; D044466:Asian People; D016022:Case-Control Studies; D002681:China; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D015810:Linkage Disequilibrium; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D020641:Polymorphism, Single Nucleotide; D011401:Promoter Regions, Genetic; D051057:Proto-Oncogene Proteins c-akt / Q000235:genetics*; D012307:Risk Factors; D013274:Stomach Neoplasms / Q000235:genetics* / Q000473:pathology; D014158:Transcription, Genetic; D055815:Young Adult
chemical_list: C494918:AKT1 protein, human; C494921:AKT2 protein, human; D051057:Proto-Oncogene Proteins c-akt
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