rs2046210

This case-control study examined 822 genetic variants in primary miRNA sequences and 10,468 variants in 38 miRNA biogenesis pathway genes in relation to breast cancer risk among women of African ancestry. The study included 1,657 cases and 2,029 controls from the ROOT consortium with replication in 3,153 cases and 2,831 controls from the AABC consortium. Key findings identified SNPs associated with overall breast cancer risk and estrogen receptor (ER)-specific risk, including rs73991220 in mir-4725 (ER-negative; OR=1.27, p=0.002), rs146287903 in PAPD4 (ER-negative; OR=0.49, p=3.27×10⁻⁴), and rs72631820 in miR-339-3p (ER-positive; OR=1.36, p=0.004).

A case-control study of 830 Korean breast cancer patients and 390 controls evaluating associations between genetic polymorphisms in estrogen receptor genes (ESR1, ESR2) and estrogen-metabolizing enzyme genes (CYP1A1, CYP1B1, COMT) with breast cancer risk. ESR1 rs2881766 (OR=1.40, p=0.02), rs2077647 (OR=1.37, p=0.02), rs926778 (OR=1.56, p≤0.01), and rs2273206 (OR=1.40, p=0.01) increased breast cancer risk, while rs3798377 (OR=0.76, p=0.05) decreased risk in overall patients. Associations varied substantially by age group and tumor subtype, with rs2881766 consistently increasing risk across all age groups except luminal B subtype.

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).

Gene-gene interaction study identifying pairwise SNP interactions influencing bone mineral density (BMD) in Caucasian and African samples. Discovery analysis in Kansas City (2,286) and Omaha (1,000) samples identified RBMS3 rs6549904 and rs7640046 interacting with ZNF516 rs4891159 with highly significant p-values (7.04×10⁻¹¹ and 1.03×10⁻¹⁰), with interaction ORs of 3.19-4.82. Replication in Framingham Heart Study confirmed findings (p=8.07×10⁻³ and p=2.91×10⁻³), though African American sample showed opposite directional effect, suggesting ancestry-dependent genetic architecture of osteoporosis.

Genome-wide association study of Ashkenazi Jewish women with familial breast cancer but no BRCA1/2 mutations identified 7 novel SNPs and confirmed 6 known variants. A 7-marker risk model including rs17663555, rs566164, rs11075884, FGFR2 haplotype (rs11200014, rs2981579, rs1078806, rs1219648, rs2420946, rs2981582), rs13387042, rs2046210 (ESR1), and rs3112612 (TOX3) achieved moderate discriminatory accuracy (AUC=0.74; 95% CI: 0.69-0.79) for predicting familial breast cancer risk in this population.

This multi-stage genome-wide association study in 11,705 BRCA1 mutation carriers identified three novel cancer risk-modifying loci: rs2290854 at 1q32 associated with breast cancer (HR=1.14), and rs17631303 (HR=1.27) and rs4691139 (HR=1.20) at 17q21.31 and 4q32.3 respectively associated with ovarian cancer. The 4q32.3 locus showed BRCA1-specific associations. These findings enable improved absolute risk estimation for BRCA1 carriers, with estimated breast cancer lifetime risks ranging from 28-50% for the lowest-risk 5% to 81-100% for the highest-risk 5%.

Population-based case-control study of 1,484 breast cancer cases and 1,307 controls examining 13 GWAS-identified SNPs for breast cancer susceptibility. Confirmed associations for 7 SNPs (rs13387042, rs4973768, rs10941679, rs2981582, rs3817198, rs3803662, rs6504950), with women in the highest quintile of a polygenic risk score having 2.2-fold increased breast cancer risk (95% CI: 1.67-2.88) compared to the lowest quintile. No significant interactions were detected between genetic loci and reproductive/menstrual risk factors.