Abstract
BACKGROUND: Single nucleotide polymorphisms (SNPs) in the progesterone receptor (PGR) gene have been associated with the risk of endometrial cancer. However, to the authors' knowledge, no study to date has systematically evaluated the role of the PGR gene in endometrial carcinogenesis. METHODS: Exposure information and DNA samples collected in the Shanghai Endometrial Cancer Study, a population-based case-control study of 1,204 incident cases and 1,212 age- and frequency-matched population controls, were used in this study. Seven tag SNPs were identified for the PGR gene plus the 5-kilobase (kb) flanking regions using the Han Chinese data from the HapMap project with a pairwise correlation coefficient (r(2)) >or= 0.90. These 7 SNPs captured 92% of SNPs in the region with a pairwise r(2) >or= 0.90 or 100% of SNPs with a pairwise r(2) >or= 0.80. Genotyping of polymorphisms was performed by using the Affymetrix MegAllele Targeted Genotyping System. A logistic regression model was used to compute adjusted odds ratios (ORs) and 95% confidence intervals (95% CIs). RESULTS: Of 7 tag SNPs that were assessed, 2 polymorphisms in the 3' flanking region of the PGR gene, reference SNP identification number (rs) 11224561 (rs11224561) and rs471767, were associated with the risk of endometrial cancer. The cytosine/cytosine (CC) genotype of SNP rs11224561 was associated with decreased risk (OR, 0.68; 95% CI, 0.50-0.92) compared with the thymine/thymine (TT) genotype. Carrying the guanine (G) allele of the rs471767 SNP also was associated with decreased risk, although the association was not statistically significant (OR, 0.78, 95%CI, 0.59-1.04 and OR, 0.32, 95%CI, 0.03-3.05 for the adenine [A]G and GG genotypes, respectively, compared with the homozygote AA). CONCLUSIONS: The current findings suggested that polymorphisms in the 3' flanking region of the PGR gene may be associated with the risk of endometrial cancer.