Radiosensitivity of Human Fibroblasts is Associated With Amino Acid Substitution Variants in Susceptible Genes And Correlates With The Number of Risk Alleles

Journal Article · Tue May 01 04:00:00 EDT 2007 · International Journal of Radiation Oncology, Biology and Physics

DOI:https://doi.org/10.1016/j.ijrobp.2006.12.050· OSTI ID:20951637

Alsbeih, Ghazi ^[1]; El-Sebaie, Medhat ^[2]; Al-Harbi, Najla ^[1]; Al-Buhairi, Muneera ^[1]; Al-Hadyan, Khaled ^[1]; Al-Rajhi, Nasser ^[2]

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1. Radiation Biology Laboratory, Department of Biomedical Physics, King Faisal Specialist Hospital and Research Centre, Riyadh (Saudi Arabia)
2. Department of Radiation Oncology, King Faisal Specialist Hospital and Research Centre, Riyadh (Saudi Arabia)

Purpose: Genetic predictive markers of radiosensitivity are being sought for stratifying radiotherapy for cancer patients and risk assessment of radiation exposure. We hypothesized that single nucleotide polymorphisms in susceptible genes are associated with, and the number of risk alleles has incremental effect on, individual radiosensitivity. Methods and Materials: Six amino acid substitution variants (ATM 1853 Asp/Asn G>A, p53 72 Arg/Pro G>C, p21 31 Ser/Arg C>A, XRCC1 399 Arg/Gln G>A, XRCC3 241 Thr/Met C>T, and TGF{beta}1 10 Leu/Pro T>C) were genotyped by direct sequencing in 54 fibroblast strains of different radiosensitivity. Results: The clonogenic survival fraction at 2 Gy range was 0.15-0.50 (mean, 0.34, standard deviation, 0.08). The mean survival fraction at 2 Gy divided the cell strains into radiosensitive (26 cases) and normal (28 controls). A significant association was observed between the survival fraction at 2 Gy and ATM 1853 Asn, XRCC3 241 Met, and TGF{beta}1 10 Leu alleles (p = 0.05, p = 0.02, and p = 0.02, respectively). The p53 72 Arg allele showed a borderline association (p = 0.07). The number of risk alleles increased with increasing radiosensitivity, and the group comparison showed a statistically significant difference between the radiosensitive and control groups (p {<=}0.001). Conclusion: The results of our study have shown that single nucleotide polymorphisms in susceptible genes influence cellular radiation response and that the number of risk alleles has a combined effect on radiosensitivity. Individuals with multiple risk alleles could be more susceptible to radiation effects than those with fewer risk alleles. These results may have implications in predicting normal tissue reactions to radiotherapy and risk assessment of radiation exposure.

• OSTI ID: 20951637
• Journal Information: International Journal of Radiation Oncology, Biology and Physics, Journal Name: International Journal of Radiation Oncology, Biology and Physics Journal Issue: 1 Vol. 68; ISSN IOBPD3; ISSN 0360-3016
• Country of Publication: United States
• Language: English

Related Subjects

63 RADIATION, THERMAL, AND OTHER ENVIRON. POLLUTANT EFFECTS ON LIVING ORGS. AND BIOL. MAT.
AMINO ACIDS
BIOLOGICAL RADIATION EFFECTS
FIBROBLASTS
GENES
HAZARDS
IONIZING RADIATIONS
MONOCLINIC LATTICES
NEOPLASMS
NUCLEOTIDES
RADIOSENSITIVITY
RADIOTHERAPY
RISK ASSESSMENT
SURVIVAL CURVES