Chromosomal radiosensitivity in young cancer patients: possible evidence of genetic predisposition

Baria, K.; Warren, C; Eden, O. B.; Roberts, Stephen A; West, Catharine M L; Scott, David

doi:10.1080/09553000110117359

Cited by 44 publications

(31 citation statements)

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“…Enhanced G 2 chromosomal radiosensitivity has been detected in several welldefined cancer susceptibility syndromes, most notably ataxia telangiectasia [Parshad and Sanford, 2001]. Increased G 2 chromosomal radiosensitivity also has been reported in a high proportion of patients with a diverse range of cancers [Scott et al, 1994a;Parshad et al, 1996;Patel et al, 1997;Scott et al, 1999;Terzoudi et al, 2000;Bondy et al, 2001;Riches et al, 2001;Baeyens et al, 2002;Baria et al, 2002] leading to suggestions that it could be a marker of cancer predisposing genes of low penetrance whose role is to respond to DNA damage Bondy et al, 2001;Baria et al, 2002]. Support for the heritability of chromosomal radiosensitivity across generations can be inferred from family studies Scott, 2000;Curwen et al, 2005].…”

Section: Introductionmentioning

confidence: 99%

Influence of polymorphisms at loci encoding DNA repair proteins on cancer susceptibility and G₂chromosomal radiosensitivity

Wilding¹,

Curwen²,

Tawn³

et al. 2006

Environ and Mol Mutagen

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Sixteen candidate polymorphisms (13 SNPs and 3 microsatellites) in nine genes from four DNA repair pathways were examined in 83 subjects, comprising 23 survivors of childhood cancer, their 23 partners, and 37 offspring, all of whom had previously been studied for G 2 chromosomal radiosensitivity. Genotype at the Asp148Glu SNP site in the APEX gene of the base excision repair (BER) pathway was associated with childhood cancer in survivors (P = 0.001, significant even after multiple test adjustment), due to the enhanced frequency of the APEX Asp148 allele among survivors in comparison to that of their partners. Analysis of variance (ANOVA) of G 2 radiosensitivity in the pooled sample, as well as family-based association test (FBAT) of the family-wise data, showed sporadic suggestions of associations between G 2 radiosensitivity and polymorphisms at two sites (the Thr241-Met SNP site in the XRCC3 gene of the homologous recombinational pathway by ANOVA, and the Ser326Cys site in the hOGG1 gene of the BER pathway by FBAT analysis), but neither of these remained significant after multiple-test adjustment. This pilot study provides an intriguing indication that DNA repair gene polymorphisms may underlie cancer susceptibility and variation in radiosensitivity. Environ. Mol. Mutagen. 48:48-57, 2007.

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Section: Introductionmentioning

confidence: 99%

Influence of polymorphisms at loci encoding DNA repair proteins on cancer susceptibility and G₂chromosomal radiosensitivity

Wilding¹,

Curwen²,

Tawn³

et al. 2006

Environ and Mol Mutagen

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“…For example, ataxia telangiectasia was originally identified in radiosensitive individuals (reviewed in Lavin and Shiloh, 1999), and recent murine studies demonstrate a predisposition to radiation-induced mammary carcinogenesis in ATM heterozygous mice , strengthening the link between genetic predisposition and radiationinduced genomic instability. Recent studies also suggest that various cancers are associated with predisposition for radiation-induced chromosomal instability Baria et al, 2002). Perhaps the strongest relationship between genetic predisposition and radiation response in human populations is the heterogeneous responses observed in occupationally and accidentally exposed populations (CBEIR, 1990;Chang et al, 1997;Salomaa et al, 1998;Lindholm et al, 1999;An and Kim, 2002;Salomaa et al, 2002;reviewed in Sankaranarayanan, 2001;Sankaranarayanan and Chakraborty, 2001), and in patients who are refractory to medical exposures to ionizing radiation (reviewed in Gudkov and Komarova, 2003).…”

Section: Introductionmentioning

confidence: 99%

Role of genetic background in induced instability

Kadhim

2003

Oncogene

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Genomic instability is effectively induced by ionizing radiation. Recently, evidence has accumulated supporting a relationship between genetic background and the radiation-induced genomic instability phenotype. This is possibly due to alterations in proteins responsible for maintenance of genomic integrity or altered oxidative metabolism. Studies in human cell lines, human primary cells, and mouse models have been performed predominantly using high linear energy transfer (LET) radiation, or high doses of low LET radiation. The interplay between genetics, radiation response, and genomic instability has not been fully determined at low doses of low LET radiation. However, recent studies using low doses of low LET radiation suggest that the relationship between genetic background and radiation-induced genomic instability may be more complicated than these same relationships at high LET or high doses of low LET radiation. The complexity of this relationship at low doses of low LET radiation suggests that more of the population may be at risk than previously recognized and may have implications for radiation risk assessment.

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“…Several studies have shown that enhanced chromosomal radiosensitivity is also present in a significant proportion of cancer patients (Scott et al, 1994(Scott et al, , 1998Parshad et al, 1996;Patel et al, 1997;Terzoudi et al, 2000;Baria et al, 2001Baria et al, , 2002Buchholz and Wu, 2001;Papworth et al, 2001;Riches et al, 2001;Baeyens et al, 2002Baeyens et al, , 2005Ban et al, 2004;Howe et al, 2005;Kolusayin Ozar and Orta, 2005;Mozdarani et al, 2005;Distel et al, 2006;Lisowska et al, 2006;Varga et al, 2006). The majority of data have been collected in studies considering breast cancer patients whose lymphocytes were irradiated in the G 2 phase of the cell cycle (Scott et al, 1994Parshad et al, 1996;Patel et al, 1997;Terzoudi et al, 2000;Baria et al, 2001;Buchholz and Wu, 2001;Riches et al, 2001;Baeyens et al, 2002Baeyens et al, , 2005Howe et al, 2005;Djuzenova et al, 2006;Docherty et al, 2007).…”

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confidence: 99%

Chromosomal radiosensitivity in head and neck cancer patients: evidence for genetic predisposition?

et al. 2008

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The association between chromosomal radiosensitivity and genetic predisposition to head and neck cancer was investigated in this study. In all, 101 head and neck cancer patients and 75 healthy control individuals were included in the study. The G 2 assay was used to measure chromosomal radiosensitivity. The results demonstrated that head and neck cancer patients had a statistically higher number of radiation-induced chromatid breaks than controls, with mean values of 1.23 and 1.10 breaks per cell, respectively (Po0.001). Using the 90th percentile of the G 2 scores of the healthy individuals as a cutoff value for chromosomal radiosensitivity, 26% of the cancer patients were radiosensitive compared with 9% of the healthy controls (P ¼ 0.008). The mean number of radiation-induced chromatid breaks and the proportion of radiosensitive individuals were highest for oral cavity cancer patients (1.26 breaks per cell, 38%) and pharynx cancer patients (1.27 breaks per cell, 35%). The difference between patients and controls was most pronounced in the lower age group (p50 years, 1.32 breaks per cell, 38%) and in the non-and light smoking patient group (p10 pack-years, 1.28 breaks per cell, 46%). In conclusion, enhanced chromosomal radiosensitivity is a marker of genetic predisposition to head and neck cancer, and the genetic contribution is highest for oral cavity and pharynx cancer patients and for early onset and non-and light smoking patients.

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Chromosomal radiosensitivity in young cancer patients: possible evidence of genetic predisposition

Cited by 44 publications

References 16 publications

Influence of polymorphisms at loci encoding DNA repair proteins on cancer susceptibility and G₂chromosomal radiosensitivity

Influence of polymorphisms at loci encoding DNA repair proteins on cancer susceptibility and G₂chromosomal radiosensitivity

Role of genetic background in induced instability

Chromosomal radiosensitivity in head and neck cancer patients: evidence for genetic predisposition?

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Chromosomal radiosensitivity in young cancer patients: possible evidence of genetic predisposition

Cited by 44 publications

References 16 publications

Influence of polymorphisms at loci encoding DNA repair proteins on cancer susceptibility and G2chromosomal radiosensitivity

Influence of polymorphisms at loci encoding DNA repair proteins on cancer susceptibility and G2chromosomal radiosensitivity

Role of genetic background in induced instability

Chromosomal radiosensitivity in head and neck cancer patients: evidence for genetic predisposition?

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Influence of polymorphisms at loci encoding DNA repair proteins on cancer susceptibility and G₂chromosomal radiosensitivity

Influence of polymorphisms at loci encoding DNA repair proteins on cancer susceptibility and G₂chromosomal radiosensitivity