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Poster display session: Basic science, Endocrine tumours, Gastrointestinal tumours - colorectal & non-colorectal, Head and neck cancer (excluding thyroid), Melanoma and other skin tumours, Neuroendocrine tumours, Thyroid cancer, Tumour biology & pathology

2026 - Fluoropyrimidine and Inflammatory Genes Promoter Methylation in Egyptian CRC patients

Date

21 Oct 2018

Session

Poster display session: Basic science, Endocrine tumours, Gastrointestinal tumours - colorectal & non-colorectal, Head and neck cancer (excluding thyroid), Melanoma and other skin tumours, Neuroendocrine tumours, Thyroid cancer, Tumour biology & pathology

Presenters

Mariam Fouad

Citation

Annals of Oncology (2018) 29 (suppl_8): viii670-viii682. 10.1093/annonc/mdy304

Authors

M.A. Fouad, S.E. Salem, M.M. Hussein, A.N. Zekri, D.M. Badr, H.F. Hafez, E. Eldesouky, S.A. Shouman

Author affiliations

  • Cancer biology, National cancer Institute-Cairo University, 11796 - Cairo/EG
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Resources

Abstract 2026

Background

Methylation of CpG islands in the promoter region of a gene is commonly associated with gene silencing and frequently observed in colorectal cancer (CRC) disease. Fluoropyrimidine (FP) based therapy received as single agent or in combination is still the backbone in CRC treatment according to the stage of the disease at diagnosis.

Methods

This prospective study was conducted on 43 Egyptian CRC patients and 32 healthy individuals. Baseline whole blood samples were collected from the patients and after 3 and 6 months of FP based therapy. Methylation specific PCR (MS- PCR) was performed for FP metabolizing genes: thymidylate synthase (TS), thymidine phosphorylase (TP), dihydropyrimidine dehydrogenase (DPD), and for the inflammatory gene: cyclooxygenase-2 (COX-2). Genes expression were calculated as fold change relative to healthy control by real time PCR.

Results

TS gene was unmethylated in 90.7 % of CRC patients who had upregulation of TS gene (median= 23.43 folds). TP gene was fully methylated in all CRC patients and upregulated by a median of 22 folds. Significant DPD down-expression (≤ 0.3 folds) was found in 58.8 % CRC patients with full DPD gene promoter methylation (P < 0.001) while significant COX-2 down-expression (≤ 5.86 folds) was encountered in 25.5 % CRC patients with partial promoter gene methylation (P = 0.006), and significantly down-expressed in 35.3 % of CRC patients with full methylation (P = 0.002).TS, DPD and COX-2 genes expression were significantly increased with FP therapy while TP expression was significantly decreased but FP therapy did not change the form of promoter genes methylation.

Conclusions

Both DPD and COX-2 genes expression were dependent on the methylation status of their promoter regions. FP therapy affects FP metabolizing and inflammatory genes expression but not the methylation status of genes promoter.

Clinical trial identification

Legal entity responsible for the study

Egyptian National Cancer Institute, Cairo University.

Funding

Egyptian National Cancer Institute, Cairo University.

Editorial Acknowledgement

Disclosure

All authors have declared no conflicts of interest.

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