TPD52 and NFKB1 gene expression levels correlate with G2 chromosomal radiosensitivity in lymphocytes of women with and at risk of hereditary breast cancer.
OBJECTIVE
To evaluate a transcriptomic approach to identify healthy women at increased risk of breast cancer due to G2-radiosensitivity and look at transcripts that are differentially expressed between individuals.


METHODS
We perform the first study to assess the association of G2 radiosensitivity with basal gene expression in cultured T-lymphocytes from 11 women with breast cancer and 12 healthy female relatives using Affymetrix GeneChips.


RESULTS
Transcripts associated with radiosensitivity and breast cancer risk were predominantly involved in innate immunity and inflammation, such as interleukins and chemokines. Genes differentially expressed in radiosensitive individuals were more similarly expressed in close family members than in un-related individuals, suggesting heritability of the trait. The expression of tumour protein D52 (TPD52), a gene implicated in cell proliferation, apoptosis, and vesicle trafficking was the most strongly correlated with G2 score while nuclear factor (kappa)-B (NFKB1) was highly inversely correlated with G2 score. NFKB1 is known to be activated by irradiation and its inhibition has been previously shown to increase radiosensitivity.


CONCLUSIONS
Gene expression analysis of lymphocytes may provide a quantitative measure of radiation response potential and is a promising marker of breast cancer susceptibility.
Sims
A H
AH
Breast Biology Group, Paterson Institute for Cancer Research, University of Manchester, UK. Andrew.H.Sims@manchester.ac.uk
Finnon
P
P
Miller
C J
CJ
Bouffler
S D
SD
Howell
A
A
Scott
D
D
Clarke
R B
RB
D001943:Breast Neoplasms / Q000235:genetics* / Q000378:metabolism*; D002875:Chromosomes / Q000235:genetics / Q000528:radiation effects*; D005260:Female; D016195:G2 Phase / Q000235:genetics / Q000528:radiation effects*; D020869:Gene Expression Profiling; D020022:Genetic Predisposition to Disease / Q000235:genetics; D006801:Humans; D052002:NF-kappa B p50 Subunit / Q000378:metabolism*; D009363:Neoplasm Proteins / Q000378:metabolism*; D011836:Radiation Tolerance / Q000235:genetics / Q000528:radiation effects; D018570:Risk Assessment / Q000379:methods; D012307:Risk Factors; D013223:Statistics as Topic; D013601:T-Lymphocytes / Q000378:metabolism*
D052002:NF-kappa B p50 Subunit; C489548:NFKB1 protein, human; D009363:Neoplasm Proteins; C114751:TPD52 protein, human