rs1256049

Candidate gene association study in Xinjiang women identifying pelvic organ prolapse (POP) susceptibility loci. Among 88 POP cases and 108 controls, ESR1 rs17847075 (OR=2.738, P=0.041) and rs2234693 (OR=2.99, P=0.024), ZFAT rs1036819 (OR=10.286, P=0.036), and protective FBLN5 rs12589592 (OR=0.111, P=0.029) showed significant associations with POP risk.

Population-based case-control study of 1,304 prostate cancer cases and 1,266 controls examining 73 SNPs in five estrogen pathway genes (ESR1, ESR2, CYP19A1, CYP1A1, CYP1B1). Only CYP1B1 rs1056836 (Val158Met) retained significance after multiple comparisons adjustment (OR=1.22, 95% CI 1.02-1.46, p=0.004). ESR1, CYP1A1, and CYP1B1 variants showed nominal associations with prostate cancer risk, and ESR2/CYP19A1 variants associated with tumor aggressiveness, though these did not persist after correction.

A meta-analysis of 80 studies (69 publications) with 26,428 cancer cases and 43,381 controls evaluating the ESR1 PvuII rs2234693 T>C polymorphism and cancer susceptibility. Overall, the T allele showed modest decreased cancer risk (OR=0.95, 95% CI=0.91-0.99), with stronger associations for specific cancer types: prostate cancer (TT vs. CC: OR=0.79), leiomyoma (T vs. C: OR=0.82), and hepatocellular carcinoma (TT vs. CC: OR=0.45). The authors conclude that ESR1 PvuII polymorphism has minimal impact on overall cancer susceptibility.

This case-control study investigated the association between the rs1256049 (Rsa) polymorphism in the estrogen receptor beta gene and rheumatoid arthritis (RA) in 263 RA patients and 174 osteoarthritis controls. The GG genotype was significantly more frequent in RA than OA patients (P = 0.008, OR = 1.501, 95% CI: 1.12-2.02), with a stronger association in severe RA patients and in women. The findings suggest the GG genotype may be a risk factor for RA development, particularly severe disease in females.

A case-control study of 114 Japanese postmenopausal women with osteoporosis and 171 controls found that minor alleles of ESR1 SNPs rs2077647 (exon 1) and rs2234693 (intron 1) were significantly associated with increased osteoporosis risk (OR 2.48-3.27). The haplotype CC at these risk SNPs showed strong association with osteoporosis (OR = 3.15, 95% CI = 1.83-5.41). Notably, moderate alcohol consumption showed a protective gene-environment interaction, reducing the genetic risk by approximately 80% (OR = 0.22, 95% CI = 0.05-0.83).

Case-control study of 462 osteoporotic patients and 336 controls examining associations between polymorphisms in ESR1, ESR2, and RIZ1 genes and vertebral fractures and bone mineral density (BMD). ESR1 variants XbaI (rs2234693) C allele and PvuII (rs9340799) G allele were associated with decreased vertebral fracture risk in women (P<0.01 and P=0.04 respectively), and the X-P-H haplotype protected against fractures (P=0.04). ESR2 rs1256031 C allele decreased BMD and AluI G allele increased fracture risk; block1haplo2 (rs1256031:T and AluI:A) increased lumbar BMD by 0.04±0.02 g/cm² and decreased fracture risk (P<0.05). RIZ1 Pro704indel showed no significant associations.

This population-based study of 4,470 breast cancer cases from the SEARCH cohort examined associations between germline polymorphisms in 6 steroid hormone metabolism genes (COMT, CYP19A1, ESR1, PGR, SULT1E1, STS) and survival after breast cancer diagnosis. A COMT polymorphism (rs4818) showed significant association with survival in a dominant model (HR=0.80, 95% CI: 0.69-0.95, p=0.009), though this was only marginally significant after permutation adjustment (p=0.047). No significant associations were found in the other genes studied.

This pooled analysis of 5,789 breast cancer cases and 7,761 controls from five prospective cohorts examined associations between estrogen receptor beta (ESR2) gene haplotypes and breast cancer risk. Using haplotype tagging SNPs, the study found that one haplotype (CCAC) was significantly associated with increased breast cancer risk (OR 1.17, 95% CI 1.07-1.28, p=0.0007, corrected p=0.002). No individual SNPs showed independent association, and the haplotype risk was primarily observed in younger women. The results suggest inherited ESR2 variants confer modest increased breast cancer susceptibility in Caucasian women.