ArticleMolecular biology reports2020
Correlation of MLH1 polymorphisms, survival statistics, in silico assessment and gene downregulation with clinical outcomes among breast cancer cases.
Article in Molecular biology reports, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 7 papers.
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Who cites it
7 citing papers in PubMed, 13 citations in OpenAlex.
- Genetic Variation ofInternational journal of dentistry · 2026Article
- MLH1 Promoter Variant -93G>A and Breast Cancer Susceptibility: Evidence from Azerbaijan.Biomedicines · 2025Article
- Genome-Wide Screening in Haploid Stem Cells Reveals Synthetic Lethality Targeting MLH1 and TP53 Deficient Tumours.Cell proliferation · 2025Article
- Molecular Basis of Breast Tumor Heterogeneity.Advances in experimental medicine and biology · 2025Review
- A novel long non-coding RNA TTN-AS1/microRNA-589-5p/FOXP1 positive feedback loop increases the proliferation, migration and invasion of pancreatic cancer cell lines.Oncology letters · 2021Article
- Correlation of MSH2 exonic deletions and protein downregulation with breast cancer biomarkers and outcome in Pakistani women/patients.Environmental science and pollution research international · 2021Article
- DNA Mismatch Repair System Imbalances in Breast Adenocarcinoma.Cancer diagnosis & prognosisReview
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Authors and funding
8 authors at 5 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
This study aimed to investigate the role of MLH1 polymorphisms, respective protein structure prediction, survival analysis, related clinicopathological details and MLH1 expression in breast cancer (BC). Genotyping of selected SNPs in BC patients (493) and age matched controls (387) were performed by Tetra-ARMS PCR. Gene expression among breast tumors (127) and adjacent control tissues were analysed using reverse transcriptase PCR (RT-PCR) and immunohistochemistry. Statistical analysis was performed by SPSS and MedCalc. Conditional logistic regression analysis was applied to compute the odds ratio and confidence interval. Phyre2 and I-TASSER were used to generate MLH1 protein structures and verified by a variety of computational tools. Genotyping illustrated that MLH1 polymorphisms (rs63749795 and rs63749820) were significantly associated (P ≤ 0.05) with risk of developing BC. Down regulation of MLH1 gene expression/loss of the MLH1 protein (OR 12; CI 2.8-53.1) was observed in BC cases, illustrating its potential role in disease development. Moreover, loss of the MLH1 protein was found to be associated with higher grade cancer (P = 0.02) and lymph node positivity (P = 0.03), highlighting its essential role, as a component of the mismatch repair (MMR) machinery. Bioinformatics analysis confirmed that nonsense mutations produce a truncated MLH1 protein, causing a reduction in MMR efficiency. No association between MLH1 polymorphisms and overall and progression free survival statistics was observed among BC cases, possibly due to short follow-up study. Results at DNA, RNA and protein levels, along with in silico analysis, highlights the potential role of MLH1 in DNA repair mechanisms, within BC. Therefore, it was concluded that MLH1 may contribute towards BC development and progression.
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