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dc.contributor.authorScott, David
dc.date.accessioned2009-10-19T15:55:46Z
dc.date.available2009-10-19T15:55:46Z
dc.date.issued2004
dc.identifier.citationChromosomal radiosensitivity and low penetrance predisposition to cancer. 2004, 104 (1-4):365-70 Cytogenet. Genome Res.en
dc.identifier.issn1424-859X
dc.identifier.pmid15162066
dc.identifier.doi10.1159/000077517
dc.identifier.urihttp://hdl.handle.net/10541/84454
dc.description.abstractThis mini-review summarises studies in this Institute on the sensitivity of cells of patients with common cancers to the chromosome-damaging effects of ionising radiation, in the context of related studies. Using the 90th percentile of healthy controls (n >200) as the cut-off point between a normal and a sensitive response, 40% of patients with breast cancer (n = 166) were sensitive when cells were irradiated in the G2 phase of the cell cycle. Smaller studies showed that patients with colorectal, head and neck (at < 45 years) and childhood cancers also exhibited degrees of enhanced sensitivity, whereas cervical and lung cancer cases did not. Cells from breast and head and neck cases irradiated in G(0) also showed increased sensitivity. We propose that such elevated sensitivity is a marker of low penetrance predisposition to cancer. The strongest support for this hypothesis was our demonstration of the Mendelian heritability of chromosomal radiosensitivity in 95 family members of breast cancer cases. Challenges for the future include more heritability studies, identification of the underlying genetic determinants, assessment of the associated cancer risk (spontaneous and radiogenic) and population screening for cancer prevention strategies.
dc.language.isoenen
dc.subjectBreast Canceren
dc.subjectColorectal Canceren
dc.subjectHead and Neck Canceren
dc.subjectCanceren
dc.subjectHereditary Cancer Syndromesen
dc.subjectCultured Tumour Cellsen
dc.subject.meshAdult
dc.subject.meshAtaxia Telangiectasia
dc.subject.meshBreast Neoplasms
dc.subject.meshCarcinoma
dc.subject.meshCell Cycle
dc.subject.meshChild
dc.subject.meshChromosomes, Human
dc.subject.meshColorectal Neoplasms
dc.subject.meshDNA Damage
dc.subject.meshDNA Repair
dc.subject.meshFamily Health
dc.subject.meshFemale
dc.subject.meshGenetic Predisposition to Disease
dc.subject.meshHead and Neck Neoplasms
dc.subject.meshHumans
dc.subject.meshLung Neoplasms
dc.subject.meshMale
dc.subject.meshNeoplasms
dc.subject.meshNeoplastic Syndromes, Hereditary
dc.subject.meshPenetrance
dc.subject.meshRadiation Tolerance
dc.subject.meshTumor Cells, Cultured
dc.subject.meshUterine Cervical Neoplasms
dc.titleChromosomal radiosensitivity and low penetrance predisposition to cancer.en
dc.contributor.departmentPaterson Institute for Cancer Research, Christie Hospital NHS Trust, Withington, Manchester, UK. david.scott2004@btinternet.comen
dc.identifier.journalCytogenetic and Genome Researchen
html.description.abstractThis mini-review summarises studies in this Institute on the sensitivity of cells of patients with common cancers to the chromosome-damaging effects of ionising radiation, in the context of related studies. Using the 90th percentile of healthy controls (n >200) as the cut-off point between a normal and a sensitive response, 40% of patients with breast cancer (n = 166) were sensitive when cells were irradiated in the G2 phase of the cell cycle. Smaller studies showed that patients with colorectal, head and neck (at < 45 years) and childhood cancers also exhibited degrees of enhanced sensitivity, whereas cervical and lung cancer cases did not. Cells from breast and head and neck cases irradiated in G(0) also showed increased sensitivity. We propose that such elevated sensitivity is a marker of low penetrance predisposition to cancer. The strongest support for this hypothesis was our demonstration of the Mendelian heritability of chromosomal radiosensitivity in 95 family members of breast cancer cases. Challenges for the future include more heritability studies, identification of the underlying genetic determinants, assessment of the associated cancer risk (spontaneous and radiogenic) and population screening for cancer prevention strategies.


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