Ethnic distribution of estrogen receptor-α polymorphism is associated with a higher prevalence of uterine leiomyomas in black Americans

ObjectiveTo investigate whether polymorphisms in the estrogen receptor α (ERα) gene are associated with an increased risk of uterine leiomyomas (ULMs).DesignGenomic DNA was isolated from normal myometrium samples collected at the time of the hysterectomy.SettingVolunteers 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 ERα gene using polymerase chain reaction and restriction fragment length polymorphism.Result(s)The ERα PP genotype was associated with a significantly increased risk of ULM in black and white women, but not in Hispanic women. Women with the ERα PP genotype were 6.42 times (confidence limits 2.04–20.16) more likely to have ULMs than other genotypes. The ERα 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 ERα 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.