Marker at the androgen receptor gene for determining breast cancer susceptibility
AssigneeSignalgene
InventorFrancois Rousseau
Life of this patent
Estimating the term…
Abstract
The present invention relates to a method of determining an individual's predisposition to breast cancer, development of breast cancer, protection against breast cancer and/or responsiveness to therapy for breast cancer. The method comprises the step of determining the androgen receptor genotype at the CAG repeat locus of an individual, or at a locus in linkage disequilibrium with the CAG repeat locus, thereby determining an individual's predisposition to breast cancer, development of breast cancer, protection against breast cancer and/or responsiveness to therapy for breast cancer.
Claims18
A method of determining an individual's predisposition to breast cancer, development of breast cancer and/or responsiveness to therapy for breast cancer, said method comprising the step of determining a polymorphism at the CAG repeat of the androgen receptor (AR) gene or a DNA variant equivalent, or mutation which shows a linkage disequilibrium therewith, whereby said polymorphism at the AR gene, or marker in linkage disequilibrium therewith enables a prediction of an individual's predisposition to breast cancer, development of breast cancer and/or responsiveness to therapy for breast cancer.
An assay for screening and selecting an agent which modulates breast cancer predisposition comprising:
- a) a recombinant androgen receptor (AR) gene or functional fragment thereof, which comprises a CAG repeat polymorphism in exon 1 thereof, or a marker in linkage disequilibrium therewith;
- and
- b) assaying a function of said androgen receptor;
- wherein an allele which modulates said function of said androgen receptor can be selected, and wherein a modulation of a function of said androgen receptor is associated with a modulation of said breast cancer predisposition, whereby short CAG repeats of said AR positively modulate androgen receptor function, while long CAG repeats of said AR negatively modulate Androgen receptor function, thereby leading to breast cancer protection or breast cancer predisposition.
An assay for screening and selecting an agent which modulates breast cancer predisposition comprising:
- a) an expression vector comprising a promoter operably linked to a reporter gene, said promoter comprising an androgen response element, said response element affecting the activity of said promoter upon binding thereto of androgen or analog thereof;
- b) a cell expressing a chosen allele of an androgen receptor and harboring said vector of a);
- c) submitting said cell to at least one agent;
- and
- d) assaying a level of said reporter gene;
- whereby an agent which modulates breast cancer predisposition can be selected when the level of said reporter gene is significantly modulated by the presence of said agent through its action through the androgen receptor.
A method for screening and selecting an agent which can modulate breast cancer predisposition comprising:
- a) selecting a specific allele of the androgen receptor (AR) gene, variant, equivalent, or mutation thereof which shows linkage disequilibrium therewith;
- b) assaying a function of said AR allele of a);
- and
- c) selecting an agent which can modulate breast cancer predisposition,
- wherein an agent which modulates AR function is selected as an agent capable of modulating breast cancer predisposition when said function is significantly different in the presence of said agent, as compared to in the absence thereof.
Dependencies are inferred from the claim text.