Shorter CAG repeat length in the AR gene is associated with poor outcome in head and neck cancer.
OBJECTIVE
Alterations in the size of the [CAG](n) repeats of the AR gene have been described in several types tumors. The purpose of this study was to evaluate if there is an association between the AR [CAG](n) repeat alleles and the relative risk for head and neck cancer and to analyse microsatellite instability (MSI) and loss of heterozygosity (LOH) in these tumors.


METHODS
Matched samples of blood and head and neck tumors were evaluated using two methodologies, silver-stained gels to perform the analyses of MSI and LOH, and automated analysis to confirm these results and for genotyping of the AR [CAG](n) repeat length. Sixty-nine individuals without cancer were used as a control group for both procedures. The Log-rank test was used to compare overall survival and disease-free survival curves. The Cox proportional hazards regression models were performed to determine the [CAG](n) repeats as an independent prognostic factor.


RESULTS
Patients with alleles <or=20 in the male group showed a correlation with lower disease-free survival (P=0.0325) and with recurrence or metastasis (RR 2.52, CI 95%). In the female group, the allele 2 (longer allele) showed a significant lower mean of [CAG](n) repeat when compared to the control group. Microsatellite instability was detected in nine cases in both procedures. In six out of these nine cases, we observed a reduction of the AR [CAG](n) repeat length. LOH was detected in one out of 17 women informative for oral cancer in both procedures.


CONCLUSIONS
These results suggest that short [CAG](n) repeat length (<or=20) polymorphism is associated with poor prognosis in a subset of male patients with head and neck cancer and that AR gene microsatellite instability is uncommon in these tumors.
Rosa
Fabíola Encinas
FE
Department of Genetics, IB-UNESP, Botucatu, São Paulo, Brazil. encinas@ibb.unesp.br
dos Santos
Rodrigo Mattos
RM
Poli-Frederico
Regina Célia
RC
Canevari
Renata de Azevedo
Rde A
Nishimoto
Inês Nobuko
IN
Magrin
José
J
Rainho
Cláudia Aparecida
CA
Kowalski
Luiz Paulo
LP
Rogatto
Silvia Regina
SR
D000225:Adenine; D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000483:Alleles; D016022:Case-Control Studies; D003596:Cytosine; D018572:Disease-Free Survival; D005260:Female; D005500:Follow-Up Studies; D006147:Guanine; D006258:Head and Neck Neoplasms / Q000235:genetics*; D006801:Humans; D019656:Loss of Heterozygosity / Q000235:genetics; D008297:Male; D053842:Microsatellite Instability; D008875:Middle Aged; D009362:Neoplasm Metastasis / Q000235:genetics; D009364:Neoplasm Recurrence, Local / Q000235:genetics; D011110:Polymorphism, Genetic / Q000235:genetics; D011379:Prognosis; D011944:Receptors, Androgen / Q000235:genetics*; D012737:Sex Factors; D015996:Survival Rate; D018911:Trinucleotide Repeats / Q000235:genetics*
D011944:Receptors, Androgen; D006147:Guanine; D003596:Cytosine; D000225:Adenine