The Effect of Estrogen-Related Genetic Variants on the Development of Uterine Leiomyoma: Meta-analysis

Uterine leiomyoma is the most common benign gynecological tumor in women of reproductive age. It has been diagnosed approximately in 5 to 69% of women and was symptomatic in 30% of them. The underlying pathobiology of uterine leiomyoma is not well understood yet, but it can be defined as an estrogen-dependent tumor. Thus, this meta-analysis aimed to investigate ESR1rs9340799 (XbaI, A351G), ESR1rs2234693 (Pvull, T397C), and COMT rs4680 (Val158Met) polymorphisms, which affect estrogen functioning and metabolism, in association with UL risk. According to PRISMA protocol, systematic searching of databases resulted 24 included studies. Pooled odds ratios (ORs) with 95% confidence intervals (CI) were used to evaluate associations of the three targeted polymorphisms with uterine leiomyoma risk in dominant model of inheritance. Meta-analysis included 4969 women diagnosed with uterine leiomyoma and 4934 controls. ESR1 (XbaI, A351G) polymorphism showed no significant association with uterine myeloma risk (OR = 1.19, 95% CI 0.98-1.45, P=0.07). ESR1 (Pvull, T397C) was associated with a higher risk of uterine leiomyoma, but only in Asian (OR =1.78, 95% CI 1.30-2.45, P = 0.0004) and COMT (Val158Met) according to our data is significantly associated with a lower risk of leiomyoma (OR = 0.83, 95% CI 0.71-0.97, P = 0.02). Our updated meta-analysis provided statistical evidence for the protective role of COMT (Val158Met) in association with the susceptibility to uterine leiomyoma and the possible role of ESR1 (Pvull, T397C) as a risk factor of this tumor.

Automated summary

This meta-analysis found that ESR1 (Pvull, T397C) is associated with an increased risk of uterine leiomyoma in Asian populations, while COMT (Val158Met) is significantly associated with a lower risk of leiomyoma.