@2024 Afarand., IRAN
ISSN: 2251-8215 Sarem Journal of Reproductive Medicine 2017;1(3):89-95
ISSN: 2251-8215 Sarem Journal of Reproductive Medicine 2017;1(3):89-95
Abberant Lymphocytes Rate after Gamma-Irradiationn as a Biomarker of Breast Cancer
ARTICLE INFO
Article Type
Original ResearchAuthors
Mojtahedi F. (1)Pooladi A. (2)
Sirati F. (3)
Kaihani E. (1)
Akhlaghpour Sh. (4)
Karimlou M. (5)
Bagherizadeh I. (6)
Fallah M. (1)
Ghasemi Firouzabadi S. (1)
Behjati F. (*)
(*) Genetic Research Center, University of Social Welfare and Rehabilitation Sciences, Tehran, Iran
(1) Genetic Research Center, University of Social Welfare and Rehabilitation Sciences, Tehran, Iran
(2) “Sarem Fertility & Infertility Research Center (SAFIR)” and “Sarem Cell Research Center (SCRC)”, Sarem Women’s Hospital, Tehran, Iran
(3) Surgery Department, Medicine Faculty, Tehran University of Medical Sciences, Tehran, Iran
(4) Navid Medical Center, Tehran, Iran
(5) Statistics Department, Medicine Faculty, University of Social Welfare and Rehabilitation Sciences, Tehran, Iran
(6) “Sarem Cell Research Center (SCRC)” and “Medical Genetics Department”, Tehran, Iran
Correspondence
Article History
Received: May 15, 2016Accepted: June 25, 2016
ePublished: August 15, 2017
ABSTRACT
Aims
The use of non-invasive laboratory tests based on detection of biomarkers in the blood samples is a good strategy for early diagnosis of breast cancer. The lymphocyte radiosensitivity assessment can be a valuable method to diagnose breast cancer. The objective of this study was to investigate the radiosensitivity indices in sporadic breast cancer among Iranian women and to evaluate the potential of those indices for clinical use in early diagnosis of breast cancer and assessing its susceptibility.
Materials & Methods The present study is a case-control that was conducted on 32 patients with sporadic breast cancer (patient group) and 30 healthy individuals (control group). The obtained blood samples of both groups were exposed to gamma-irradiation (0.4 Gy) and the level of chromosome breakage was determined based on the G2 chromosome breakage assay protocol. In the metaphase lymphocytes, the percentage of the abnormal cells was calculated as the radiosensitivity index for comparing the two groups. Data were analyzed by SPSS 19 software using student t-test, paired t-test, chi-square and Fisher exact test.
Findings There was a significant difference in the percentage of the index of the abnormal cells after irradiation between two groups (p=0.001). The area under the curve (AUC) of the percentage of the abnormal cells and odds ratio (OR) were found as 0.725 with 3.818, respectively. The frequency of increased radiosensitivity based on this index (at 61% cut-off point), was 65.6% in the patients and about 33% in the control group.
Conclusion The increased level of chromosome breakage following irradiation with gamma rays can be used as an early diagnostic biomarker of breast cancer or a possible indicator for breast cancer susceptibility.
Materials & Methods The present study is a case-control that was conducted on 32 patients with sporadic breast cancer (patient group) and 30 healthy individuals (control group). The obtained blood samples of both groups were exposed to gamma-irradiation (0.4 Gy) and the level of chromosome breakage was determined based on the G2 chromosome breakage assay protocol. In the metaphase lymphocytes, the percentage of the abnormal cells was calculated as the radiosensitivity index for comparing the two groups. Data were analyzed by SPSS 19 software using student t-test, paired t-test, chi-square and Fisher exact test.
Findings There was a significant difference in the percentage of the index of the abnormal cells after irradiation between two groups (p=0.001). The area under the curve (AUC) of the percentage of the abnormal cells and odds ratio (OR) were found as 0.725 with 3.818, respectively. The frequency of increased radiosensitivity based on this index (at 61% cut-off point), was 65.6% in the patients and about 33% in the control group.
Conclusion The increased level of chromosome breakage following irradiation with gamma rays can be used as an early diagnostic biomarker of breast cancer or a possible indicator for breast cancer susceptibility.
Keywords:
Breast Neoplasms ,
Gamma Iradiation,
Chromosome Aberration ,
Chromosome Breakage ,
Biomarker ,
CITATION LINKS
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[15]Roberts SA, Spreadborough AR, Bulman B, Barber JB, Evans DG, Scott D. Heritability of cellular radiosensitivity: A marker of low penetrance predisposition genes in breast cancer?. Am J Hum Genet. 1999;65(3):784-94.
[16]Boostma D, Kraemer KH, Cleaver JE, Hoeijmakers JHJ. Nucleotide Excision Repair Syndromes: Xeroderma Pigmentosum, Cockayne Syndrome, and Trichothiodystrophy. In: The Metabolic and Molecular Bases of Inherited Disease. 6th ed. New York: McGraw-Hill; 1989.
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[20]Scott D, Barber JB, Levine EL, Burrill W, Roberts SA. Radiation-induced micronucleus induction in lymphocytes identifies a high frequency of radiosensitive cases among breast cancer patients: A test for predisposition?. Br J Cancer. 1998;77(4):614-20.
[21]Rigaud O, Guedeney G, Duranton I, Leroy A, Doloy MT, Magdelenat H. Genotoxic effects of radiotherapy and chemotherapy on the circulating lymphocytes of breast cancer patients. II. Alteration of DNA repair and chromosome radiosensitivity. Mutat Res. 1990;242(1):25-35.
[22]Samouhos E. Chromosomes, cancer and radiosensitivity. Am J Clin Oncol. 1983;6(4):503-6.
[23]Riches AC, Bryant PE, Steel CM, Gleig A, Robertson AJ, Preece PE, et al. Chromosomal radiosensitivity in G2- phase lymphocytes identifies breast cancer patients with distinctive tumour characteristics. Br J Cancer. 2001;85(8):1157–61.
[24]Terzoudi GI, Jung T, Hain J, Vrouvas J, Margaritis K, Donta-Bakoyianni C, et al. Increased G2 chromosomal radiosensitivity in cancer patients: The role of cdk1/cyclin-B activity level in the mechanisms involved. Int J Radiat Biol. 2000;76(5):607-15.
[25]Parshad R, Price FM, Bohr VA, Cowans KH, Zujewski JA, Sanford KK. Deficient DNA repair capacity, apredisposing factor in breast cancer. Br J Cancer. 1996;74(1):1–5.
[26]Scott D, Spreadborough A, Levine E, Roberts SA. Genetic predisposition in breast cancer. Lancet. 1994;344(8934):1444.
[27]Abdel-RahmanSZ, El-Zein RA. Evaluating the effects of genetic variants of DNA repair genes using cytogenetic mutagen sensitivity approaches. Biomarkers. 2011;16(5):393-404.
[28]Cadwell KK, Curwen GB, Tawn EJ, Winther JF, Boice JD Jr. G2 checkpoint control and G2 chromosomal radiosensitivity in cancer survivors and their families. Mutagenesis. 2011;26(2):291-4.
[29]Kotsopoulos J, Chen Z, Vallis KA, Poll A, Ainsworth P, Narod SA. DNA repair capacity as a possible biomarker of breast cancer risk in female BRCA1 mutation carriers. Br J Cancer. 2007;96(1):118–25.
[30]Baria K, Warren C, Roberts SA, West CM, Scott D. Chromosomal radiosensitivity as a marker of predisposition to common cancers?. Br J Cancer. 2001;84(7):892–6.
[31]Hill JW, Tansavatdi K, Lockett KL, Allen GO, Takita C, Pollack A, et al. Validation of the cell cycle G(2) delay assay in assessing ionizing radiation sensitivity and breast cancer risk. Cancer Manag Res. 2009;1:39-48.
[32]Ryabchenko NM, Glavin OA, Shtefura V, Anikushko MF. Chromosomal radiosensitivity in Ukrainian breast cancer patients and healthy individuals. Exp Oncol. 2012;34(2):121-4.
[33]Wilson PF, Nagasawa H, Fitzek MM, Little JB, Bedford JS. G2-phase chromosomal radiosensitivity of primary fibroblasts from hereditary retinoblastoma family members and some apparently normal controls. Radiat Res. 2010;173(1):62-70.
[34]Hille A, Hofman-Huther H, Kuhnle E, Wilken B, Rave-Frank M, Schmidberger H, et al. Spontaneous and radiation-induced chromosomal instability and persistence of chromosomeaberrations after radiotherapy in lymphocytes from prostate cancer patients. Radiat Environ Biophys. 2010;49(1):27-37.
[35]De Ruyck K, de Gelder V, Van Eijkeren M, Boterberg T, De Neve W, Vral A, et al. Chromosomal radiosensitivity in head and neck cancer patients: Evidence for genetic predisposition?. Br J Cancer. 2008;98(10):1723-38.
[2]Miller A. Causes of breast cancer and high-risk groups. In: Harris JR. Breast Diseases. 2th ed. Philadelphia: JB Lippincott; 1991. p. 119.
[3]Santora LM, Mahoney MC, Lawvere S, Englert JJ, Symons AB, Mirand AL. Breast cancer screening beliefs by practice location. BMC Public Health. 2003; 3: 9.
[4]Taylor AMR. Chromosome instability syndromes. Clin haematol. 2001;14(3):631-44.
[5]Haskell CM. Cancer Treatment. 5th ed. Saunders WB, editor. Philadelphia: W.B. Saunders; 2001.
[6]Kahan E, Ibrahim AS, Najjar KE, Ron E, Al-Agha H, Polliack A, et al. Cancer Patterns in the Middle East Special Report from the Middle East Cancer Society. Acta Oncol. 1997;36(6):631-6.
[7]Pichierri P, Franchitto A, Palitti F. Predisposition to cancer and radiosensitivity. Genet Mol Biol. 2000;23(4):1101-5.
[8]Smart V, Curwen GB, Whitehouse CA, Edwards A, Tawn EJ. Chromosomal radiosensitivity: A study of the chromosomal G(2) assay in human blood lymphocytes indicating significant inter-individual variability. Mutat Res. 2003;528(1-2):105-10.
[9]Bryant PE, Gray L, Riches AC, Steel CM, Finnon P, Howe O, et al. The G2 chromosomal radiosensitivity assay. Int J Radiat Biol. 2002;78(9):863-6.
[10]Docherty Z, Georgiou A, Langman C, Kesterton I, Rose S, Camplejohn R, et al. Is chromosome radiosensitivity and apoptotic response to irradiation correlated with cancer susceptibility?. Int J Radiat Biol. 2007;83(1):1-12.
[11]Barwell J, Pangon L, Georgiou A, Kesterton I, Langman C, Arden- Jones A, et al. Lymphocyte radiosensitivity in BRCA1 and BRCA2 mutation carriers and implications for breast cancer susceptibility. Int J Cancer. 2007;121(7):1631-6.
[12]Baeyens A, Thierens H, Claes K, Poppe B, Messiaen L, De Ridder L, et al. Chromosomal radiosensitivity in breast cancer patients with a known or putative genetic predisposition. Br J Cancer. 2002;87(12):1379-85.
[13]Scott D, Barber JB, Spreadborough AR, Burrill W, Roberts SA. Increased chromosomal radiosensitivity in breast cancer patients: A comparison of two assays. Int J Radiat Biol. 1999;75(1):1-10.
[14]Barber JB, Burrill W, Spreadborough AR, Levine E, Warrenb C, Kiltie AE, et al. Relationship between in vitro chromosomal radiosensitivity of peripheral blood lymphocytes and the expression of normal tissue damage following radiotherapy for breast cancer. Radiother Oncol. 2000;55(2):179-86.
[15]Roberts SA, Spreadborough AR, Bulman B, Barber JB, Evans DG, Scott D. Heritability of cellular radiosensitivity: A marker of low penetrance predisposition genes in breast cancer?. Am J Hum Genet. 1999;65(3):784-94.
[16]Boostma D, Kraemer KH, Cleaver JE, Hoeijmakers JHJ. Nucleotide Excision Repair Syndromes: Xeroderma Pigmentosum, Cockayne Syndrome, and Trichothiodystrophy. In: The Metabolic and Molecular Bases of Inherited Disease. 6th ed. New York: McGraw-Hill; 1989.
[17]Cleaver JE. Xeroderma pigmentosum: A human disease in which an initial stage of DNA repair is defective. Proc Natl Acad Sci U S A. 1969;63(2):428-35.
[18]Rary JM, Bender MA, Kelly TE. Cytogenetic status of ataxia telangiectasia. Am J Hum Genet. 1974;26:70
[19]Sanford KK, Parshad R, Price FM, Jones GM, Tarone RE, Eierman L, et al. Enhanced chromatid damage in blood lymphocytes after G2 phase x irradiation, a marker of the ataxia-telangiectasia gene. J Natl Cancer Inst. 1990;82(12):1050-4.
[20]Scott D, Barber JB, Levine EL, Burrill W, Roberts SA. Radiation-induced micronucleus induction in lymphocytes identifies a high frequency of radiosensitive cases among breast cancer patients: A test for predisposition?. Br J Cancer. 1998;77(4):614-20.
[21]Rigaud O, Guedeney G, Duranton I, Leroy A, Doloy MT, Magdelenat H. Genotoxic effects of radiotherapy and chemotherapy on the circulating lymphocytes of breast cancer patients. II. Alteration of DNA repair and chromosome radiosensitivity. Mutat Res. 1990;242(1):25-35.
[22]Samouhos E. Chromosomes, cancer and radiosensitivity. Am J Clin Oncol. 1983;6(4):503-6.
[23]Riches AC, Bryant PE, Steel CM, Gleig A, Robertson AJ, Preece PE, et al. Chromosomal radiosensitivity in G2- phase lymphocytes identifies breast cancer patients with distinctive tumour characteristics. Br J Cancer. 2001;85(8):1157–61.
[24]Terzoudi GI, Jung T, Hain J, Vrouvas J, Margaritis K, Donta-Bakoyianni C, et al. Increased G2 chromosomal radiosensitivity in cancer patients: The role of cdk1/cyclin-B activity level in the mechanisms involved. Int J Radiat Biol. 2000;76(5):607-15.
[25]Parshad R, Price FM, Bohr VA, Cowans KH, Zujewski JA, Sanford KK. Deficient DNA repair capacity, apredisposing factor in breast cancer. Br J Cancer. 1996;74(1):1–5.
[26]Scott D, Spreadborough A, Levine E, Roberts SA. Genetic predisposition in breast cancer. Lancet. 1994;344(8934):1444.
[27]Abdel-RahmanSZ, El-Zein RA. Evaluating the effects of genetic variants of DNA repair genes using cytogenetic mutagen sensitivity approaches. Biomarkers. 2011;16(5):393-404.
[28]Cadwell KK, Curwen GB, Tawn EJ, Winther JF, Boice JD Jr. G2 checkpoint control and G2 chromosomal radiosensitivity in cancer survivors and their families. Mutagenesis. 2011;26(2):291-4.
[29]Kotsopoulos J, Chen Z, Vallis KA, Poll A, Ainsworth P, Narod SA. DNA repair capacity as a possible biomarker of breast cancer risk in female BRCA1 mutation carriers. Br J Cancer. 2007;96(1):118–25.
[30]Baria K, Warren C, Roberts SA, West CM, Scott D. Chromosomal radiosensitivity as a marker of predisposition to common cancers?. Br J Cancer. 2001;84(7):892–6.
[31]Hill JW, Tansavatdi K, Lockett KL, Allen GO, Takita C, Pollack A, et al. Validation of the cell cycle G(2) delay assay in assessing ionizing radiation sensitivity and breast cancer risk. Cancer Manag Res. 2009;1:39-48.
[32]Ryabchenko NM, Glavin OA, Shtefura V, Anikushko MF. Chromosomal radiosensitivity in Ukrainian breast cancer patients and healthy individuals. Exp Oncol. 2012;34(2):121-4.
[33]Wilson PF, Nagasawa H, Fitzek MM, Little JB, Bedford JS. G2-phase chromosomal radiosensitivity of primary fibroblasts from hereditary retinoblastoma family members and some apparently normal controls. Radiat Res. 2010;173(1):62-70.
[34]Hille A, Hofman-Huther H, Kuhnle E, Wilken B, Rave-Frank M, Schmidberger H, et al. Spontaneous and radiation-induced chromosomal instability and persistence of chromosomeaberrations after radiotherapy in lymphocytes from prostate cancer patients. Radiat Environ Biophys. 2010;49(1):27-37.
[35]De Ruyck K, de Gelder V, Van Eijkeren M, Boterberg T, De Neve W, Vral A, et al. Chromosomal radiosensitivity in head and neck cancer patients: Evidence for genetic predisposition?. Br J Cancer. 2008;98(10):1723-38.