Hyperandrogenism, mediated by obesity and receptor polymorphisms, promotes aggressive epithelial ovarian cancer biology.
OBJECTIVE
Epidemiologic data suggest that aberrant androgen homeostasis may promote aggressive epithelial ovarian cancer biology. Hyperandrogenism results from both obesity and expression of polymorphic androgen receptor (AR) allelotypes harboring short cytosine-adenine-guanine (CAG) repeat sequences; both have been shown to independently correlate with poor overall survival in ovarian cancer. We have hypothesized that the combination of these factors further manifests an aggressive ovarian cancer phenotype.


METHODS
Genotype analysis of the AR CAG polymorphism was performed on 81 patients with papillary serous epithelial ovarian cancer. Medical records were reviewed for body mass index (BMI), clinico-pathologic factors, and survival. Data were examined using the Fishers exact test, Kaplan-Meier survival, and Cox regression analyses.


RESULTS
Overweight or obese women (BMI > or = 25) with a short AR allele (< or = 19 CAG repeats) demonstrated statistically shorter progression-free survival (9 months) when compared to underweight or ideal body weight women (BMI < 25) and a long AR allele (> 19 CAG repeats; 26 months, p=0.0002). Overweight/obese women with a short AR allele also demonstrated shorter overall survival (34 months) when compared to underweight/ideal body weight women with a long AR allele (59 months, p=0.036). On multivariate analyses, the combination of a short AR allele and BMI > 25 was an independent poor prognostic factor after controlling for age, stage, grade, optimal cytoreduction, and AR allele length and BMI independently (p=0.05).


CONCLUSIONS
These data provide further evidence that suggest that hyperandrogenism promotes an aggressive epithelial ovarian cancer phenotype.
Li
Andrew J
AJ
Department of Obstetrics and Gynecology, Division of Gynecologic Oncology, Cedars-Sinai Medical Center, 8700 Beverly Blvd, Suite 160W, Los Angeles, CA 90048, USA. Andrew.Li@cshs.org
Elmore
R Geoffrey
RG
Pavelka
James C
JC
Karlan
Beth Y
BY
D000483:Alleles; D015331:Cohort Studies; D018292:Cystadenoma, Papillary / Q000150:complications / Q000235:genetics / Q000473:pathology; D018293:Cystadenoma, Serous / Q000150:complications / Q000235:genetics / Q000473:pathology; D005260:Female; D005838:Genotype; D006801:Humans; D017588:Hyperandrogenism / Q000150:complications / Q000235:genetics* / Q000473:pathology; D008875:Middle Aged; D009367:Neoplasm Staging; D009765:Obesity / Q000150:complications / Q000235:genetics* / Q000473:pathology; D010051:Ovarian Neoplasms / Q000150:complications / Q000235:genetics* / Q000473:pathology; D011110:Polymorphism, Genetic; D011944:Receptors, Androgen / Q000235:genetics*; D018911:Trinucleotide Repeats