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.