title: Genetic Polymorphisms of TGFB1, TGFBR1, SNAI1 and TWIST1 Are Associated with Endometrial Cancer Susceptibility in Chinese Han Women.
abstract: Endometrial cancer (EC) is a complex disease involving multiple gene-gene and gene-environment interactions. TGF-β signaling plays pivotal roles in EC development. This study aimed to investigate whether the genetic polymorphisms of TGF-β signaling related genes TGFB1, TGFBR1, SNAI1 and TWIST1 contribute to EC susceptibility. Using the TaqMan Genotyping Assay, 19 tagging-SNPs of these four genes were genotyped in 516 EC cases and 707 controls among Chinese Han women. Logistic regression (LR) showed that the genetic variants of TGFB1 rs1800469, TGFBR1 rs6478974 and rs10733710, TWIST1 rs4721745 were associated with decreased EC risk, and these four loci showed a dose-dependent effect (Ptrend < 0.0001). Classification and regression tree (CART) demonstrated that women carrying both the genotypes of TGFBR1 rs6478974 TT and rs10512263 TC/CC had the highest risk of EC (aOR = 7.86, 95% CI = 3.42-18.07, P<0.0001). Multifactor dimensionality reduction (MDR) revealed that TGFB1 rs1800469 plus TGFBR1 rs6478974 was the best interactional model to detect EC risk. LR, CART and MDR all revealed that TGFBR1 rs6478974 was the most important protective locus for EC. In haplotype association study, TGFBR1 haplotype CACGA carrier showed the lowest EC risk among women with longer menarche-first full term pregnancy intervals (˃11 years) and BMI˂24 (aOR = 0.39, 95% CI = 0.17-0.90, P = 0.0275). These results suggest that polymorphisms in TGFB1, TGFBR1, SNAI1 and TWIST1 may modulate EC susceptibility, both separately and corporately.
authors.affiliation: Department of Pathology, Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Peking University Health Science Center, Beijing, China.|Department of Pathology, Peking University Third Hospital, Beijing, China.
authors.forename: Li
authors.initials: L
authors.lastname: Yang
authors.affiliation: Department of Pathology, Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Peking University Health Science Center, Beijing, China.|Department of Pathology, Peking University Third Hospital, Beijing, China.
authors.forename: Ya-Jun
authors.initials: YJ
authors.lastname: Wang
authors.affiliation: Department of Pathology, Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Peking University Health Science Center, Beijing, China.
authors.forename: Li-Yuan
authors.initials: LY
authors.lastname: Zheng
authors.affiliation: Department of Pathology, Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Peking University Health Science Center, Beijing, China.|Department of Pathology, Peking University Third Hospital, Beijing, China.
authors.forename: Yu-Mian
authors.initials: YM
authors.lastname: Jia
authors.affiliation: Department of Pathology, Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Peking University Health Science Center, Beijing, China.|Department of Pathology, Peking University Third Hospital, Beijing, China.
authors.forename: Yi-Lin
authors.initials: YL
authors.lastname: Chen
authors.affiliation: Department of Pathology, Beijing Hospital, Beijing, China.
authors.forename: Lan
authors.initials: L
authors.lastname: Chen
authors.affiliation: Department of Pathology, Beijing Hospital, Beijing, China.
authors.forename: Dong-Ge
authors.initials: DG
authors.lastname: Liu
authors.affiliation: Department of Pathology, Peking University School of Oncology, Beijing Cancer Hospital & Institute, Beijing, China.
authors.forename: Xiang-Hong
authors.initials: XH
authors.lastname: Li
authors.affiliation: Department of Gynecology, Peking University Third Hospital, Beijing, China.
authors.forename: Hong-Yan
authors.initials: HY
authors.lastname: Guo
authors.affiliation: Key Laboratory of Genomic and Precision Medicine, Chinese Academy of Sciences, Beijing, China.
authors.forename: Ying-Li
authors.initials: YL
authors.lastname: Sun
authors.affiliation: Department of Pathology, Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Peking University Health Science Center, Beijing, China.|Department of Pathology, Peking University Third Hospital, Beijing, China.
authors.forename: Xin-Xia
authors.initials: XX
authors.lastname: Tian
authors.affiliation: Department of Pathology, Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Peking University Health Science Center, Beijing, China.|Department of Pathology, Peking University Third Hospital, Beijing, China.
authors.forename: Wei-Gang
authors.initials: WG
authors.lastname: Fang
mesh_terms: D044466:Asian People / Q000235:genetics*; D015992:Body Mass Index; D016022:Case-Control Studies; D016889:Endometrial Neoplasms / Q000235:genetics*; D004843:Epistasis, Genetic; D005006:Ethnicity / Q000235:genetics; D005260:Female; D005799:Genes, Dominant; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease; D006239:Haplotypes / Q000235:genetics; D006801:Humans; D015810:Linkage Disequilibrium / Q000235:genetics; D016015:Logistic Models; D008957:Models, Genetic; D058011:Multifactor Dimensionality Reduction; D015999:Multivariate Analysis; D009687:Nuclear Proteins / Q000235:genetics*; D010802:Phylogeny; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D017346:Protein Serine-Threonine Kinases / Q000235:genetics*; D000077293:Receptor, Transforming Growth Factor-beta Type I; D018125:Receptors, Transforming Growth Factor beta / Q000235:genetics*; D012307:Risk Factors; D000071250:Snail Family Transcription Factors / Q000235:genetics*; D053773:Transforming Growth Factor beta1 / Q000235:genetics*; D051879:Twist-Related Protein 1 / Q000235:genetics*
chemical_list: D009687:Nuclear Proteins; D018125:Receptors, Transforming Growth Factor beta; C000604407:SNAI1 protein, human; D000071250:Snail Family Transcription Factors; C508960:TGFB1 protein, human; C103173:TWIST1 protein, human; D053773:Transforming Growth Factor beta1; D051879:Twist-Related Protein 1; D017346:Protein Serine-Threonine Kinases; D000077293:Receptor, Transforming Growth Factor-beta Type I; C000625841:TGFBR1 protein, human