Heritability of cellular radiosensitivity: a marker of low-penetrance predisposition genes in breast cancer?
AuthorsRoberts, Stephen A
Spreadborough, Anne R
Barber, James B P
Evans, D Gareth R
AffiliationCancer Research Campaign Biomathematics and Computing Unit, Paterson Institute for Cancer Research, Christie Hospital NHS Trust, Manchester M20 4BX, United Kingdom. email@example.com
MetadataShow full item record
AbstractMany inherited cancer-prone conditions show an elevated sensitivity to the induction of chromosome damage in cells exposed to ionizing radiation, indicative of defects in the processing of DNA damage. We earlier found that 40% of patients with breast cancer and 5%-10% of controls showed evidence of enhanced chromosomal radiosensitivity and that this sensitivity was not age related. We suggested that this could be a marker of cancer-predisposing genes of low penetrance. To further test this hypothesis, we have studied the heritability of radiosensitivity in families of patients with breast cancer. Of 37 first-degree relatives of 16 sensitive patients, 23 (62%) were themselves sensitive, compared with 1 (7%) of 15 first-degree relatives of four patients with normal responses. The distribution of radiosensitivities among the family members showed a trimodal distribution, suggesting the presence of a limited number of major genes determining radiosensitivity. Segregation analysis of 95 family members showed clear evidence of heritability of radiosensitivity, with a single major gene accounting for 82% of the variance between family members. The two alleles combine in an additive (codominant) manner, giving complete heterozygote expression. A better fit was obtained to a model that includes a second, rarer gene with a similar, additive effect on radiosensitivity, but the data are clearly consistent with a range of models. Novel genes involved in predisposition to breast cancer can now be sought through linkage studies using this quantitative trait.
CitationHeritability of cellular radiosensitivity: a marker of low-penetrance predisposition genes in breast cancer? 1999, 65 (3):784-94 Am. J. Hum. Genet.
JournalAmerican Journal of Human Genetics
- Chromosomal radiosensitivity in young cancer patients: possible evidence of genetic predisposition.
- Authors: Baria K, Warren C, Eden OB, Roberts SA, West CM, Scott D
- Issue date: 2002 May
- Chromosomal radiosensitivity as a marker of predisposition to common cancers?
- Authors: Baria K, Warren C, Roberts SA, West CM, Scott D
- Issue date: 2001 Apr 6
- Cancer predisposition, radiosensitivity and the risk of radiation-induced cancers. IV. Prediction of risks in relatives of cancer-predisposed individuals.
- Authors: Chakraborty R, Little MP, Sankaranarayanan K
- Issue date: 1998 May
- Elevated G2 chromosomal radiosensitivity in Irish breast cancer patients: a comparison with other studies.
- Authors: Howe OL, Daly PA, Seymour C, Ormiston W, Nolan C, Mothersill C
- Issue date: 2005 May
- Increased radiosensitivity as an indicator of genes conferring breast cancer susceptibility.
- Authors: Varga D, Vogel W, Bender A, Surowy H, Maier C, Kreienberg R, Deissler H, Sauer G
- Issue date: 2007 Dec