Genetic Polymorphisms of TGFB1, TGFBR1, SNAI1 and TWIST1 Are Associated with Endometrial Cancer Susceptibility in Chinese Han Women
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.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2016 |
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| Erschienen: |
2016 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:11 |
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| Enthalten in: |
PloS one - 11(2016), 5 vom: 02., Seite e0155270 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Yang, Li [VerfasserIn] |
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| Links: |
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| Anmerkungen: |
Date Completed 10.07.2017 Date Revised 07.12.2022 published: Electronic-eCollection Citation Status MEDLINE |
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| doi: |
10.1371/journal.pone.0155270 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM260274682 |
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| 100 | 1 | |a Yang, Li |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a Genetic Polymorphisms of TGFB1, TGFBR1, SNAI1 and TWIST1 Are Associated with Endometrial Cancer Susceptibility in Chinese Han Women |
| 264 | 1 | |c 2016 | |
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| 500 | |a Date Revised 07.12.2022 | ||
| 500 | |a published: Electronic-eCollection | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a 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 | ||
| 650 | 4 | |a Journal Article | |
| 650 | 7 | |a Nuclear Proteins |2 NLM | |
| 650 | 7 | |a Receptors, Transforming Growth Factor beta |2 NLM | |
| 650 | 7 | |a SNAI1 protein, human |2 NLM | |
| 650 | 7 | |a Snail Family Transcription Factors |2 NLM | |
| 650 | 7 | |a TGFB1 protein, human |2 NLM | |
| 650 | 7 | |a TWIST1 protein, human |2 NLM | |
| 650 | 7 | |a Transforming Growth Factor beta1 |2 NLM | |
| 650 | 7 | |a Twist-Related Protein 1 |2 NLM | |
| 650 | 7 | |a Protein Serine-Threonine Kinases |2 NLM | |
| 650 | 7 | |a EC 2.7.11.1 |2 NLM | |
| 650 | 7 | |a Receptor, Transforming Growth Factor-beta Type I |2 NLM | |
| 650 | 7 | |a EC 2.7.11.30 |2 NLM | |
| 650 | 7 | |a TGFBR1 protein, human |2 NLM | |
| 650 | 7 | |a EC 2.7.11.30 |2 NLM | |
| 700 | 1 | |a Wang, Ya-Jun |e verfasserin |4 aut | |
| 700 | 1 | |a Zheng, Li-Yuan |e verfasserin |4 aut | |
| 700 | 1 | |a Jia, Yu-Mian |e verfasserin |4 aut | |
| 700 | 1 | |a Chen, Yi-Lin |e verfasserin |4 aut | |
| 700 | 1 | |a Chen, Lan |e verfasserin |4 aut | |
| 700 | 1 | |a Liu, Dong-Ge |e verfasserin |4 aut | |
| 700 | 1 | |a Li, Xiang-Hong |e verfasserin |4 aut | |
| 700 | 1 | |a Guo, Hong-Yan |e verfasserin |4 aut | |
| 700 | 1 | |a Sun, Ying-Li |e verfasserin |4 aut | |
| 700 | 1 | |a Tian, Xin-Xia |e verfasserin |4 aut | |
| 700 | 1 | |a Fang, Wei-Gang |e verfasserin |4 aut | |
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