Shorter CAG repeat in the AR gene is associated with atypical hyperplasia and breast carcinoma.
BACKGROUND
Previous reports into the role of [CAG]n repeat lengths in the androgen receptor (AR) gene indicate that these may play an important part in the development and progression of breast cancer, however, knowledge regarding benign breast lesions is limited.


METHODS
PCR-based GeneScan analysis was used to investigate the [CAG]n repeat length at exon 1 of the AR gene in 59 benign breast lesions (27 fibroadenomas, 18 atypical hyperplasias, and 14 hyperplasias without atypia) and 54 ductal breast carcinomas. Seventy-two cancer-free women were used as a control group. In addition, [CAG]n repeats were evaluated for the presence of loss of heterozygosity (LOH) and microsatellite instability (MSI) in a subset of these samples (27 fibroadenomas, 14 hyperplasias without atypia and 22 breast carcinomas).


RESULTS
Shorter [CAG]n repeat lengths were strongly correlated with atypical hyperplasias (p = 0.0209) and carcinomas (p < 0.0001). LOH was found in 1/12 and 4/20 informative cases of hyperplasias without atypia and breast carcinomas, respectively. Three patients with breast carcinoma who had previously presented atypical hyperplasia showed a reduction in the [CAG]n repeat length in their carcinomas.


CONCLUSIONS
Short [CAG]n repeat length (< or = 20) polymorphisms are strongly associated with breast carcinomas and atypical hyperplasias. Although non-significant, a subgroup of patients with breast carcinoma and genotype SS showed an association with parameters of worse outcome.
De Abreu
Francine Blumental
FB
Department of Genetics, Institute of Biosciences, São Paulo State University, UNESP, Botucatu, SP, Brazil.
Pirolo
Leandro Júnior
LJ
Canevari
Renata de Azevedo
Rde A
Rosa
Fabíola Encinas
FE
Moraes Neto
Francisco Alves
FA
Caldeira
José Roberto Fígaro
JR
Rainho
Claudia Aparecida
CA
Rogatto
Silvia Regina
SR
D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000483:Alleles; D001940:Breast / Q000473:pathology; D001943:Breast Neoplasms / Q000235:genetics* / Q000473:pathology; D018270:Carcinoma, Ductal, Breast / Q000235:genetics / Q000473:pathology; D005260:Female; D018226:Fibroadenoma / Q000235:genetics / Q000473:pathology; D006801:Humans; D006965:Hyperplasia / Q000235:genetics / Q000473:pathology; D008875:Middle Aged; D016133:Polymerase Chain Reaction; D011110:Polymorphism, Genetic; D011944:Receptors, Androgen / Q000235:genetics*; D018911:Trinucleotide Repeats
D011944:Receptors, Androgen