Among 45 variants in 11 genes, HDM2 promoter polymorphisms emerge as new candidate biomarker associated with radiation toxicity.
Due to individual variations in radiosensitivity, biomarkers are needed to tailor radiation treatment to cancer patients. Since single nucleotide polymorphisms (SNPs) are frequent in human, we hypothesized that SNPs in genes that mitigate the radiation response are associated with radiotoxicity, in particular late complications to radiotherapy and could be used as genetic biomarkers for radiation sensitivity. A total of 155 patients with nasopharyngeal cancer were included in the study. Normal tissue fibrosis was scored using RTOG/EORTC grading system. Eleven candidate genes (ATM, XRCC1, XRCC3, XRCC4, XRCC5, PRKDC, LIG4, TP53, HDM2, CDKN1A, TGFB1) were selected for their presumed influence on radiosensitivity. Forty-five SNPs (12 primary and 33 neighboring) were genotyped by direct sequencing of genomic DNA. Patients with severe fibrosis (cases, G3-4, n = 48) were compared to controls (G0-2, n = 107). Results showed statistically significant (P < 0.05) association with radiation complications for six SNPs (ATM G/A rs1801516, HDM2 promoter T/G rs2279744 and T/A rs1196333, XRCC1 G/A rs25487, XRCC5 T/C rs1051677 and TGFB1 C/T rs1800469). We conclude that these six SNPs are candidate genetic biomarkers for radiosensitivity in our patients that have cumulative effects as patients with severe fibrosis harbored significantly higher number of risk alleles than the controls (P < 0.001). Larger cohort, independent replication of these findings and genome-wide association studies are required to confirm these results in order for SNPs to be used as biomarkers to individualize radiotherapy on genetic basis.
Radiation Biology, Biomedical Physics Department, King Faisal Specialist Hospital and Research Centre, MBC-03, P.O. Box 3354, Riyadh, 11211, Saudi Arabia. galsbeih@kfshrc.edu.sa.
Ghazi
G
Alsbeih
Radiation Oncology, King Faisal Specialist Hospital and Research Centre, Riyadh, 11211, Saudi Arabia.
Medhat
M
El-Sebaie
Radiation Oncology, King Faisal Specialist Hospital and Research Centre, Riyadh, 11211, Saudi Arabia.
Nasser
N
Al-Rajhi
Radiation Biology, Biomedical Physics Department, King Faisal Specialist Hospital and Research Centre, MBC-03, P.O. Box 3354, Riyadh, 11211, Saudi Arabia.
Najla
N
Al-Harbi
Radiation Biology, Biomedical Physics Department, King Faisal Specialist Hospital and Research Centre, MBC-03, P.O. Box 3354, Riyadh, 11211, Saudi Arabia.
Khaled
K
Al-Hadyan
Radiation Biology, Biomedical Physics Department, King Faisal Specialist Hospital and Research Centre, MBC-03, P.O. Box 3354, Riyadh, 11211, Saudi Arabia.
Sara
S
Al-Qahtani
College of Applied Medical Sciences, King Saud University, Riyadh, 11211, Saudi Arabia.
Mohammad
M
Alsubael
Radiation Oncology, King Faisal Specialist Hospital and Research Centre, Riyadh, 11211, Saudi Arabia.
Mohammad
M
Al-Shabanah
Radiation Biology, Biomedical Physics Department, King Faisal Specialist Hospital and Research Centre, MBC-03, P.O. Box 3354, Riyadh, 11211, Saudi Arabia.
Belal
B
Moftah
Fibrosis; Late reactions to radiotherapy; Nasopharyngeal carcinoma; Radiosensitivity; Single nucleotide polymorphism (SNP)