HFE variants in colorectal cancer and their clinicopathological correlations
| Autor: | S. M. K. Gamage, Sharmin Aktar, Farhadul Islam, Cu T. Lu, Lakal Dissabandara, Katherine Ting-Wei Lee, Chamath D. Ranaweera, Vinod Gopalan, Tracie Cheng, Alfred King-Yin Lam |
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| Rok vydání: | 2021 |
| Předmět: |
Adult
Male congenital hereditary and neonatal diseases and abnormalities Colorectal cancer Pathological staging Adenocarcinoma medicine.disease_cause Pathology and Forensic Medicine symbols.namesake medicine Humans Clinical significance Hemochromatosis Protein Aged Sanger sequencing Mutation business.industry nutritional and metabolic diseases Cancer Microsatellite instability Middle Aged medicine.disease Real-time polymerase chain reaction Cancer research symbols Female Colorectal Neoplasms business |
| Zdroj: | Human Pathology. 117:9-30 |
| ISSN: | 0046-8177 |
| DOI: | 10.1016/j.humpath.2021.07.013 |
| Popis: | Summary The study aimed to screen mutation of human homeostatic iron regulator (HFE) in colorectal carcinoma (CRC) and detect their associations with clinicopathological parameters. Expression of HFE was determined by quantitative polymerase chain reaction in matched CRC and non neoplastic colorectal mucosal tissue of 76 patients. Genomic DNA extracted were subjected to high high-resolution melt curve analysis and Sanger sequencing to detect mutations in HFE. The associations of the identified mutations with a variety of clinical features were determined. Approximately 60% of CRC showed low HFE expression. Of the ten 10 mutations identified in exons 2 and 4, c.187C>G (H63D), c845G>A (C282Y), c.193A>T (S65C), g.3828T>C, g.5795T>C, and g.5728G>A were known mutations. Four novel mutations were discovered; : c.184G>A, c.220T>G, c.322A>C, and c.324T>C. Heterozygous H63D and C282Y mutations were seen in 71% and 49% of cancer tissue, respectively. Tumour site (p = 0.048) and gender (p = 0.039) were significantly associated with H63D and C282Y mutation status, respectively. Local spread of cancer was significantly associated with C282Y mutations in CRC cancer and adjacent non-neoplastic tissue (p = 0.029 & and p = 0.004, respectively). There was a statistically significant association between H63D and C282Y negativity in matched non-neoplastic colorectal mucosa tissue and pathological staging of cancer (p = 0.047 & and p = 0.001, respectively). Patients with H63D and C282Y mutations in cancer tissue tend to have higher survival rates. Hence HFE mutations are common in CRC and are associated with clinicopathological parameters, implying the potential clinical significance of HFE mutations in colorectal carcinogenesis. |
| Databáze: | OpenAIRE |
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