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

Objective: To investigate whether polymorphisms in the estrogen receptor alpha (ER alpha) 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 ER alpha gene using polymerase chain reaction and restriction fragment length polymorphism. Result(s): The ER alpha PP genotype was associated with a significantly increased risk of ULM in black and white women, but not in Hispanic women. Women with the ER alpha PP genotype were 6.42 times (confidence limits 2.04-20.16) more likely to have ULMs than other genotypes. The ER alpha 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 ER alpha 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.