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

Abstract

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: Themore » 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.« less

Authors:
 [1];  [2];  [3];  [3];  [3];  [2]
  1. Radiation Biology Laboratory, Department of Biomedical Physics, King Faisal Specialist Hospital and Research Centre, Riyadh (Saudi Arabia). E-mail: galsbeih@kfshrc.edu.sa
  2. Department of Radiation Oncology, King Faisal Specialist Hospital and Research Centre, Riyadh (Saudi Arabia)
  3. Radiation Biology Laboratory, Department of Biomedical Physics, King Faisal Specialist Hospital and Research Centre, Riyadh (Saudi Arabia)
Publication Date:
OSTI Identifier:
20951637
Resource Type:
Journal Article
Resource Relation:
Journal Name: International Journal of Radiation Oncology, Biology and Physics; Journal Volume: 68; Journal Issue: 1; Other Information: DOI: 10.1016/j.ijrobp.2006.12.050; PII: S0360-3016(07)00058-2; Copyright (c) 2007 Elsevier Science B.V., Amsterdam, Netherlands, All rights reserved; Country of input: International Atomic Energy Agency (IAEA)
Country of Publication:
United States
Language:
English
Subject:
63 RADIATION, THERMAL, AND OTHER ENVIRONMENTAL POLLUTANT EFFECTS ON LIVING ORGANISMS AND BIOLOGICAL MATERIALS; AMINO ACIDS; BIOLOGICAL RADIATION EFFECTS; FIBROBLASTS; GENES; HAZARDS; IONIZING RADIATIONS; MONOCLINIC LATTICES; NEOPLASMS; NUCLEOTIDES; RADIOSENSITIVITY; RADIOTHERAPY; RISK ASSESSMENT; SURVIVAL CURVES

Citation Formats

Alsbeih, Ghazi, El-Sebaie, Medhat, Al-Harbi, Najla, Al-Buhairi, Muneera, Al-Hadyan, Khaled, and Al-Rajhi, Nasser. Radiosensitivity of Human Fibroblasts is Associated With Amino Acid Substitution Variants in Susceptible Genes And Correlates With The Number of Risk Alleles. United States: N. p., 2007. Web. doi:10.1016/j.ijrobp.2006.12.050.
Alsbeih, Ghazi, El-Sebaie, Medhat, Al-Harbi, Najla, Al-Buhairi, Muneera, Al-Hadyan, Khaled, & Al-Rajhi, Nasser. Radiosensitivity of Human Fibroblasts is Associated With Amino Acid Substitution Variants in Susceptible Genes And Correlates With The Number of Risk Alleles. United States. doi:10.1016/j.ijrobp.2006.12.050.
Alsbeih, Ghazi, El-Sebaie, Medhat, Al-Harbi, Najla, Al-Buhairi, Muneera, Al-Hadyan, Khaled, and Al-Rajhi, Nasser. Tue . "Radiosensitivity of Human Fibroblasts is Associated With Amino Acid Substitution Variants in Susceptible Genes And Correlates With The Number of Risk Alleles". United States. doi:10.1016/j.ijrobp.2006.12.050.
@article{osti_20951637,
title = {Radiosensitivity of Human Fibroblasts is Associated With Amino Acid Substitution Variants in Susceptible Genes And Correlates With The Number of Risk Alleles},
author = {Alsbeih, Ghazi and El-Sebaie, Medhat and Al-Harbi, Najla and Al-Buhairi, Muneera and Al-Hadyan, Khaled and Al-Rajhi, Nasser},
abstractNote = {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.},
doi = {10.1016/j.ijrobp.2006.12.050},
journal = {International Journal of Radiation Oncology, Biology and Physics},
number = 1,
volume = 68,
place = {United States},
year = {Tue May 01 00:00:00 EDT 2007},
month = {Tue May 01 00:00:00 EDT 2007}
}