Associations of gene‑wide SNPs in SNAI1 and TWIST1 with breast cancer and ovarian cancer susceptibility among Chinese Han women
| Autor: | Xianghong Li, Ying‑Li Sun, Yun‑Tao Xie, Rui Song, Fang Mei, Dong‑Ge Liu, Li Yang, Xin‑Xia Tian, Zi‑Fan Wang, Ya‑Jun Wang, Li‑Yuan Zheng, Lan Chen, Yue‑Hang Geng, Wei‑Gang Fang |
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| Rok vydání: | 2018 |
| Předmět: |
Adult
Cancer Research China animal structures Single-nucleotide polymorphism Breast Neoplasms Biology Polymorphism Single Nucleotide Breast cancer Asian People Polymorphism (computer science) medicine Humans Genetic Predisposition to Disease Allele Gene Genetic Association Studies Genetics Ovarian Neoplasms Multifactor dimensionality reduction Twist-Related Protein 1 Case-control study Cancer Nuclear Proteins General Medicine Middle Aged medicine.disease Oncology Case-Control Studies Female Snail Family Transcription Factors Protein Binding |
| Zdroj: | Oncology reports. 40(6) |
| ISSN: | 1791-2431 |
| Popis: | Extensive evidence suggests that the genetic etiologies of breast cancer (BC) and ovarian cancer (OC) show a certain degree of similarity. This study aimed to find out whether the single nucleotide polymorphisms (SNPs) of genes SNAI1 and TWIST1 may affect BC and OC susceptibility. A total of 7 tagging‑SNPs (tSNPs) were directly genotyped in 1,161 BC cases, 286 OC cases and 1,273 cancer‑free controls among Chinese Han women. Twenty‑eight variants in these 2 genes were genotyped by 'in silico' genotype imputation. Logistic regression (LR) revealed that tSNPs SNAI1 rs6125849, TWIST1 rs4721746 and TWIST1 rs4721745 were protective genetic variants for BC/OC. Allelic association tests of gene‑wide SNPs demonstrated that the minor alleles of SNAI1 rs6125849, TWIST1 rs4721745 and TWIST1 rs11973396 were strongly associated with BC/OC susceptibility. Multivariate LR presented that SNAI1 rs6125849, TWIST1 rs4721745, rs4721746 and rs11973396 affected BC/OC susceptibility independently, and women harboring all four protective genoytpes had the lowest risk. Multifactor dimensionality reduction analysis further showed that SNAI1 rs6125849 and TWIST1 rs4721745 had the strongest synergistic interaction. Functional annotation predicted that the minor alleles of SNAI1 rs6125849 and TWIST1 rs4721745 altered their binding affinities with transcription factors E2F6 and TCF11‑MafG respectively. These results indicate that genetic variants in SNAI1 and TWIST1, most probably SNAI1 rs6125849 and TWIST1 rs4721745, may modulate BC and OC susceptibility. |
| Databáze: | OpenAIRE |
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