No significant association between progesterone receptor exon 4 Val660Leu G/T polymorphism and risk of ovarian cancer

Epidemiological studies suggest that ovarian cancer is an endocrine-related tumour, and progesterone exposure specifically may decrease the risk of ov arian cancer. To assess whether the progesterone receptor (PR) exon 4 valin e to leucine amino acid variant is associated with specific tumour characte ristics or with overall risk of ovarian cancer, we examined 551 cases of ep ithelial ovarian cancer and 298 unaffected controls for the underlying G--> T nucleotide substitution polymorphism. Stratification of the ovarian cance r cases according to tumour behaviour (low malignant potential or invasive) , histology, grade or stage failed to reveal any heterogeneity with respect to the genotype defined by the PR exon 4 polymorphism. Furthermore, the ge notype distribution did not differ significantly between ovarian cancer cas es and unaffected controls. Compared with the GG genotype, the age-adjusted odds ratio (95% confidence interval) for risk of ovarian cancer was 0.78 ( 0.57-1.08) for the GT genotype, and 1.39 (0.47-4.14) for the TT genotype. I n conclusion, the PR exon 4 codon 660 leucine variant encoded by the T alle le does not appear to be associated with ovarian tumour behaviour, histolog y, stage or grade. This variant is also not associated with an increased ri sk of ovarian cancer, and is unlikely to be associated with a large decreas e in ovarian cancer risk, although we cannot rule out a moderate inverse as sociation between the GT genotype and ovarian cancer.