rs1042838

Case-control study of 167 preeclampsia patients and 115 healthy Bavarian controls examining associations between hormone pathway SNPs and preeclampsia risk. Found rs10895068 (G/A genotype) in the progesterone receptor gene significantly more frequent in preeclampsia cases (16% vs 6%, P=0.023). No significant associations observed for rs1042838, rs488133, rs10046, or rs4646.

Meta-analysis of 12 case-control studies (3,321 subjects: 1,323 cases/1,998 controls) evaluates the PROGINS polymorphism (rs1042838) in the progesterone receptor gene and endometriosis risk. Overall results showed a trend toward increased risk of endometriosis with the variant allele in homozygous/recessive models (OR 1.41-1.43, p=0.15-0.17), less pronounced in dominant/co-dominant models (OR 1.22, p=0.11-0.15). European subgroups showed consistent significant associations (OR 1.52-2.72, p=0.0008-0.03), while Brazilian studies showed protective effects (OR 0.70-0.74, p=0.54-0.61), suggesting population-specific genetic background effects.

A hospital-based case-control study in rural and urban India (1,204 cases; 1,212 controls) examined genetic and lifestyle risk factors for breast cancer. Four SNPs in FGFR2 (rs1219648, rs2420946, rs2981575, rs2981582) showed positive associations with breast cancer (ORs 1.32-1.47). Additional SNPs in obesity and metabolic genes (rs374748 in FBN2, rs2922763 in HNF4G, rs2116830 in KCNMA1, rs11121832 in MTHFR, rs16886165 in MAP3K1, rs11594610 in TCF7L2, rs2274459 in MLN) were associated with increased breast cancer risk. Waist-to-hip ratio ≥0.95 showed strong association (OR 3.78; 95% CI 2.92-4.89), and women living first 20 years in rural areas showed protective effect (OR 0.77).

This population genetics study genotyped 289 individuals from 21 global populations for four progesterone receptor (PGR) gene variants (rs10895068, rs561650, rs608995, and the Alu insertion in PROGINS haplotype). The study found significant positive correlations between allele frequencies and female reproductive cancer incidence: the Alu insertion showed strong correlation with breast cancer (r=0.86) and ovarian cancer (r=0.53), while the rs10895068 A variant correlated with ovarian (r=0.73) and breast cancer (r=0.57). These findings suggest PGR genetic variation may contribute to global patterns of reproductive cancer incidence.

Case-control study of 483 women investigating polymorphisms in estrogen metabolism and pathway genes associated with recurrent miscarriage. The CYP19A1 rs10046 C/C genotype showed significant association with increased risk of recurrent miscarriage (P=0.017), with women carrying T/T genotype experiencing multiple miscarriages in 11.7% of cases versus 3.3% for C/C genotype. No associations were found for other CYP19A1 variants (rs4646, rs700519) or ESR1 (rs3020314) and PGR (rs1042838) polymorphisms.

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.

A population-based case-control study of 1,204 endometrial cancer cases and 1,212 controls from Shanghai examined associations between 7 tag SNPs in the progesterone receptor (PGR) gene and endometrial cancer risk. Two SNPs in the 3' flanking region were associated with reduced cancer risk: rs11224561 CC genotype (OR=0.68, 95% CI=0.50-0.92) and rs471767 G allele (OR per allele=0.77, 95% CI=0.58-1.01). A trend of decreasing risk with increasing minor alleles was observed (P for trend=0.02).