ATM mutations in female breast cancer patients predict for an increase in radiation-induced late effects

Iannuzzi, Christopher; Atencio, David P.; Green, Sheryl; Stock, Richard G.; Rosenstein, Barry S.

doi:10.1016/s0360-3016(01)02684-0

Cited by 149 publications

(56 citation statements)

References 36 publications

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“…Radiosensitivity and chemosensitivity and ATM Radiosensitivity is also a hallmark of the A-T syndrome (35,36). Increased toxicity to radiotherapy has been reported in patients with A-T syndrome and heterozygous carriers of ATM mutations, probably due to defective DNA repair and genomic instability in normal tissues (37)(38)(39)(40). However, heterozygous germ-line mutations apparently do not contribute to secondary cancers following radiotherapy (41)(42)(43).…”

Section: Germ-line Atm Heterozygosity and Cancer Susceptibilitymentioning

confidence: 99%

ATM Mutations in Cancer: Therapeutic Implications

Choi¹,

Kipps²,

Kurzrock³

2016

Molecular Cancer Therapeutics

376

318

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Activation of checkpoint arrest and homologous DNA repair are necessary for maintenance of genomic integrity during DNA replication. Germ-line mutations of the ataxia telangiectasia mutated (ATM) gene result in the well-characterized ataxia telangiectasia syndrome, which manifests with an increased cancer predisposition, including a 20% to 30% lifetime risk of lymphoid, gastric, breast, central nervous system, skin, and other cancers. Somatic ATM mutations or deletions are commonly found in lymphoid malignancies, as well as a variety of solid tumors. Such mutations may result in chemotherapy resistance and adverse prognosis, but may also be exploited by existing or emerging targeted therapies that produce synthetic lethal states.

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Section: Germ-line Atm Heterozygosity and Cancer Susceptibilitymentioning

confidence: 99%

ATM Mutations in Cancer: Therapeutic Implications

Choi¹,

Kipps²,

Kurzrock³

2016

Molecular Cancer Therapeutics

376

318

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“…268 controls screened for IVS10-6T>G Shafman et al (2000) ATM screened in 57 bilateral breast cancer cases Laake et al (2000) 483 breast cancer cases screened for 6 ATM variants Teraoka et al (2001) ATM screened in 177 breast cancer cases and 81 controls Dork et al (2001) ATM screened in 192 breast cancer cases. 1000 controls screened for variants found in cases Iannuzzi et al (2002) ATM screened in 46 breast cancer cases Sommer et al (2002) ATM screened in 43 breast cancer cases and 43 controls Maillet et al(2002) ATM screened in 94 breast cancer cases diagnosed o40 years. 140 controls screened for variants found in case Offit et al (2002) ATM screened in 37 cases with Hodgkin's disease, 10 of whom also had breast cancer.…”

Section: Molecular Evidence For Breast Cancer Risk In Atm Heterozygotesmentioning

confidence: 99%

ATM and breast cancer susceptibility

2006

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ATM was originally identified by positional cloning as the gene that underlies the autosomal recessive condition ataxia-telangiectasia. The encoded protein plays a central role in the complex processes that repair DNA doublestrand breaks. Nearly 20 years ago, epidemiological surveys of relatives of ataxia-telangiectasia cases suggested that female relatives were at modestly increased risk of breast cancer. Subsequently, many studies have tried to clarify the role of ATM in breast cancer susceptibility, but have produced inconclusive and/or inconsistent results. Recently, large epidemiological and molecular studies have finally provided conclusive evidence that ATM mutations that cause ataxia-telangiectasia are breast cancer susceptibility alleles.

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“…Several studies have reported a possible correlation between genetic polymorphisms and adverse radiotherapy reactions in patients (4)(5)(6)(7)(8)(9)(10)(11)(12). Although most studies have not detected a conclusive correlation between genotype and clinical radiosensitivity, Price et al have reported a highly significant association between clinical radiosensitivity and rare microsatellites (unusually large or unusually small alleles) in the DNA repair genes XRCC1 and XRCC3 (13).…”

Section: Introductionmentioning

confidence: 99%

Microsatellite Polymorphisms in DNA Repair GenesXRCC1, XRCC3andXRCC5in Patients with Gynecological Tumors: Association with Late Clinical Radiosensitivity and Cancer Incidence

Ruyck

Wilding²,

Eijkeren

et al. 2005

Radiation Research

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This study investigates the association of microsatellite polymorphisms in XRCC1, XRCC3 and XRCC5 with the development of late radiation-induced radiotherapy reactions and examines the correlation between these microsatellites and cancer incidence. Sixty-two women with cervical or endometrial cancer treated with radiotherapy were included in the study. According to the CTCAEv3.0 scale, 22 patients showed late adverse radiotherapy reactions (grade 2 or more). PCR on lymphocyte DNA followed by automated fragment analysis was performed to examine the number of tandem repeat units at each locus. No significant association was found between the repeat length at any of the microsatellites in XRCC1, XRCC3 or XRCC5 and the incidence of late radiotherapy complications. Since higher odds ratios (ORs) were found for the rare XRCC1 [AC] 11 and [AC] 21 repeats (OR ‫؍‬ 2.65, P ‫؍‬ 0.325 and OR ‫؍‬ 8.67, P ‫؍‬ 0.093, respectively), the possible involvement of these small and large repeats in clinical radiosensitivity cannot be completely ruled out. When specific numbers of repeats were examined, no significant correlation was found between the microsatellite repeat length in XRCC1 and XRCC5 and cancer incidence. A weak correlation between XRCC3 [AC] 16 homozygotes and cancer incidence was found (OR ‫؍‬ 2.56, P ‫؍‬ 0.055). A large-scale multicenter study of cancer patients with a high number of radiosensitive individuals is needed to clarify the value of rare polymorphic microsatellite repeats in XRCC1 and XRCC3 as a biomarker of clinical radiosensitivity or increased cancer risk.

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ATM mutations in female breast cancer patients predict for an increase in radiation-induced late effects

Cited by 149 publications

References 36 publications

ATM Mutations in Cancer: Therapeutic Implications

ATM Mutations in Cancer: Therapeutic Implications

ATM and breast cancer susceptibility

Microsatellite Polymorphisms in DNA Repair GenesXRCC1, XRCC3andXRCC5in Patients with Gynecological Tumors: Association with Late Clinical Radiosensitivity and Cancer Incidence

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