Progesterone receptor gene polymorphisms and risk of endometriosis: results from an international collaborative effort

Abstract

Objective: To investigate the association between self-reported endometriosis and the putative functional promoter +331C/T single nucleotide polymorphism and the PROGINS allele.

Design: Control subjects from ovarian cancer case-control studies participating in the international Ovarian Cancer Association Consortium. The majority of controls are drawn from population-based studies.

Setting: An international ovarian cancer consortium including studies from Australia, Europe, and the United States.

Patient(s): Five thousand eight hundred twelve white female controls, of whom 348 had endometriosis, from eight ovarian cancer case-control studies.

Intervention(s): None.

Main outcome measure(s): Genotypes for the +331C/T single nucleotide polymorphism and PROGINS allele and a history of endometriosis.

Result(s): The occurrence of endometriosis was reduced in women carrying one or more copies of the +331 T allele (odds ratio=0.65; 95% confidence interval: 0.43-0.98), whereas there was no association between the PROGINS allele and endometriosis (odds ratio=0.94, 95% confidence interval 0.76-1.16).

Conclusion(s): Additional studies of the +331C/T variant are warranted given the current finding and the equivocal results of previous studies. The +331 T allele has been shown to result in a reduced progesterone (P) receptor A to P receptor B ratio, and if the observed association with endometriosis is confirmed it would suggest that this ratio is important for this disease.

Figure 1

Forrest plot of the association between the +331 T allele and risk of endometriosis for the eight included studies. The summary odds ratio is 0.65 (95% CI 0.43, 0.98, p=0.042).