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).

DESIGN

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

SETTING

Volunteers in an academic research environment.

PATIENT(S): One hundred ninety-eight women with surgically confirmed ULMs and 229 matched controls with nonfibroid uteri.

INTERVENTION(S): Hysterectomy samples were collected from volunteers.

MAIN OUTCOME MEASURE(S): The two PvuII and XbaI intronic polymorphisms in the ERalpha gene using polymerase chain reaction and restriction fragment length polymorphism.

RESULT(S): 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.

CONCLUSION(S): 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.