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

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.