The polymorphic CAG repeat of the androgen receptor gene: a potential role in breast cancer in women over 40
| Autor: | Rose Lumbroso, Lenore K. Beitel, Mark Trifiro, Bruce Gottlieb, Leonard Pinsky, William D. Foulkes, Youssef A. Elhaji |
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| Rok vydání: | 2002 |
| Předmět: |
Adult
Cancer Research medicine.medical_specialty medicine.drug_class Mammary gland Population Breast Neoplasms Biology Germline Breast cancer Trinucleotide Repeats Internal medicine medicine Humans Allele education Aged Aged 80 and over education.field_of_study Polymorphism Genetic Middle Aged Androgen medicine.disease Androgen receptor Endocrinology medicine.anatomical_structure Oncology Estrogen Receptors Androgen Disease Progression Female |
| Zdroj: | Breast cancer research and treatment. 70(2) |
| ISSN: | 0167-6806 |
| Popis: | Previous investigations into the relationship of CAG-repeat lengths in the androgen receptor (AR) gene to female breast cancer (BC) have yielded somewhat confusing results. Decreased AR transactivational activity lowers androgen:estrogen balance, and may thereby effect functional hyperestrogenicity. This may promote the pathogenesis of BC. To elucidate whether longer CAG repeats of the AR gene (AR), which correlate with lower transactivational activity of the AR, are associated with BC in women over 40, we examined the distribution of CAG-repeat lengths in BC tissue from this population. The BC tissue was histologically graded as: Grade 1, well differentiated (WD); Grade 2, moderately differentiated (MD); and Grade 3, poorly-differentiated (PD). Analysis showed significant differences as compared to controls when CAG lengths greater than 21 were examined, and that alleles with > or = 26 repeats were 2.4-fold more frequent in BC samples than in constitutional samples from a normal population. A significant shift to greater CAG-repeat lengths, appeared in WD and MD tumors only. Our results give some indication as to the progression of BC by suggesting that hypotransactive ARs with long polyglutamine (polyGln) tracts may have a role in the initiation and/or progression of BC. PD tumors tended to have shorter than normal CAG-repeat lengths. In this case it is hypothesized that the ARs have now become hypertransactive, possibly coinciding with the estrogen resistance that is associated with PD tumors. Whether this shift is of germline or somatic origin was not clear, though the appearance in 14% of the BC samples of a third CAG-repeat length indicates that it may be somatic. |
| Databáze: | OpenAIRE |
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