rs3803662

A case-control study of 503 breast cancer patients and 503 healthy controls in northwest Chinese Han population found that rs17530068 (LOC105377871) increases breast cancer risk (p=0.047, OR=1.23, 95% CI=1.00-1.50 in log-additive model), and rs4784227 (CASC16) significantly increases risk of lymph node metastasis in breast cancer patients (p=0.025, OR=1.51, 95% CI=1.05-2.17 for allele model; p=0.008, OR=1.99, 95% CI=1.20-3.31 in codominant model).

This case-control study evaluated rare copy number variants (CNVs), protein-truncating variants, and missense mutations in DNA damage response genes for breast cancer association in Finnish cohorts. CYP2C19 deletion showed enrichment in triple-negative breast cancer (p=0.021). TEX15 c.7253dupT frameshift variant associated with hereditary breast cancer (p=0.018). FANCD2 c.2715+1G>A splice-site variant (rs201811817) showed 7.5-fold increased risk (p=0.036, OR=7.5). RECQL p.Ile156Met and POLG p.Leu392Val (rs145289229) missense variants also associated with breast cancer (p=0.043 and p=0.010, OR=2.1 respectively).

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).

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%.

A two-stage genome-wide association study (GWAS) identified six novel breast cancer susceptibility loci in a Canadian cohort (3,064 total participants). In Stage I, 348 cases and 348 controls were genotyped on Affymetrix SNP 6.0 arrays (906,600 SNPs), with 35 candidate variants selected for replication in Stage II (1,153 cases and 1,215 controls). Six SNPs showed significant association with breast cancer: rs1092913 in ROPN1L (OR 1.45, p=1.89×10⁻⁶), three ZNF577 SNPs (rs10411161, rs3848562, rs11878583; ORs 1.35-1.42), rs1429142 near EDNRA (OR 1.27), and rs1981867 near C16orf61 (OR 1.22). While not significant after genome-wide correction, these represent potential novel candidate loci warranting further validation.

Hemminki et al. (2010) conducted a case-control study of 1,415 German familial breast cancer patients and 1,830 controls to validate low-risk breast cancer susceptibility variants. The study found significant associations with FGFR2 (OR=1.43, p=1.24×10⁻¹²), TNRC9 (OR=1.33, p=1.54×10⁻⁷), and LSP1 variants. Notably, homozygous carriers showed higher risks: FGFR2 OR=2.05 and TNRC9 OR=1.62, while LSP1 showed a protective effect (OR=0.49) in homozygous carriers.

This PhD thesis presents a comprehensive study of microRNA (miRNA) SNPs and their association with breast cancer risk in Australian Caucasian populations. The study identified three key findings: rs2910164 in MIR146A showed significant association (p=0.03 and p=0.00013 in two populations); rs353291 in MIR145 showed significant differences in allele frequencies (p=0.041 and p=0.023); and rs4284505/rs7336610 in the MIR17HG cluster showed significant association with protective effect (OR=0.75, 95% CI: 0.60-0.94, p=0.012).

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.

This case-control study examined whether seven breast cancer susceptibility alleles (in FGFR2, TNRC9, MAP3K1, LSP1, and chromosomal regions 8q24 and 2q35) were associated with epithelial ovarian cancer risk. The pooled analysis of 1,383 ovarian cancer cases and 1,804 controls found no significant associations between these variants and ovarian cancer risk, with OR estimates for FGFR2 rs1219648 of 1.06 (95% CI=0.95-1.18) and rs2981582 of 1.04 (95% CI=0.93-1.15), suggesting that breast cancer risk alleles may be specific to breast cancer.

A nested case-control study of 692 invasive endometrial cancer cases and 1,723 controls within the Nurses' Health Study and Women's Health Study investigated whether seven breast cancer risk alleles were also associated with endometrial cancer risk. In contrast to breast cancer, the authors found an inverse association with rs2981582 (FGFR2) and endometrial cancer risk (OR=0.75, 95% CI: 0.60-0.95), and non-significant inverse associations with rs889312 (MAP3K1, OR=0.85) and rs1219648 (FGFR2, OR=0.86). No associations were observed with the other four SNPs, suggesting important biological differences between endometrial and breast cancer despite their shared hormone-related etiology.