Ethnic distribution of estrogen receptor-alpha polymorphism is associated with a higher prevalence of uterine leiomyomas in black Americans.
OBJECTIVE
To investigate whether polymorphisms in the estrogen receptor alpha (ERalpha) gene are associated with an increased risk of uterine leiomyomas (ULMs).


METHODS
Genomic DNA was isolated from normal myometrium samples collected at the time of the hysterectomy.


METHODS
Volunteers in an academic research environment.


METHODS
One hundred ninety-eight women with surgically confirmed ULMs and 229 matched controls with nonfibroid uteri.


METHODS
Hysterectomy samples were collected from volunteers.


METHODS
The two PvuII and XbaI intronic polymorphisms in the ERalpha gene using polymerase chain reaction and restriction fragment length polymorphism.


RESULTS
The ERalpha PP genotype was associated with a significantly increased risk of ULM in black and white women, but not in Hispanic women. Women with the ERalpha PP genotype were 6.42 times (confidence limits 2.04-20.16) more likely to have ULMs than other genotypes. The ERalpha PP genotype was also significantly associated with larger tumor burden (>400 g). The overall prevalence of the PP genotype was significantly higher in black women (35%) than white (13%) or Hispanic (16%) women. Myometrial cell lines expressing the PP genotype exhibited enhanced proliferative response to estrogen in vitro compared with their pp counterparts.


CONCLUSIONS
The ERalpha PP genotype is a genetic risk factor for ULM development among surgically treated women. The higher prevalence of this genotype in blacks might explain the increased occurrence of this tumor among black women.
Al-Hendy
Ayman
A
Department of Obstetrics and Gynecology, University of Texas Medical Branch, Galveston 77555-0587, USA. ayalhend@utmb.edu
Salama
Salama A
SA
D001741:Black or African American / Q000706:statistics & numerical data*; D014408:Biomarkers, Tumor / Q000235:genetics; D004252:DNA Mutational Analysis / Q000379:methods; D047628:Estrogen Receptor alpha / Q000235:genetics*; D005260:Female; D020022:Genetic Predisposition to Disease / Q000208:ethnology / Q000235:genetics; D005820:Genetic Testing / Q000379:methods*; D006801:Humans; D007889:Leiomyoma / Q000208:ethnology* / Q000235:genetics / Q000378:metabolism*; D011110:Polymorphism, Genetic; D015995:Prevalence; D018570:Risk Assessment / Q000379:methods; D012307:Risk Factors; D014481:United States / Q000453:epidemiology; D014594:Uterine Neoplasms / Q000453:epidemiology* / Q000235:genetics / Q000378:metabolism*
D014408:Biomarkers, Tumor; D047628:Estrogen Receptor alpha