rs1011970

A two-phase association study of 1,414 SNPs in steroid hormone and IGF-1 metabolism genes investigated breast cancer in situ (BCIS) risk in 1,062 cases and 10,126 controls from the Breast and Prostate Cancer Cohort Consortium. INSR-rs10500204 showed significant association with increased BCIS risk (OR=1.96 for homozygous major allele, p=1.68×10⁻⁵), being more strongly associated with BCIS than invasive disease. Two other SNPs (ACVR2A-rs2382112 and MAST2-rs12124649) showed nominally significant but less robust associations.

This pooled analysis of 872 women from two studies (Susan G. Komen Tissue Bank and BREAST Stamp Project) investigated the association between 62 established breast cancer susceptibility SNPs and terminal duct lobular unit (TDLU) involution, a breast cancer risk factor. Six SNPs (9.7%) showed nominal associations with at least one TDLU measure: rs616488 (PEX14), rs11242675 (FOXQ1), and rs6001930 (MKL1) with higher TDLU count (P=0.047, 0.045, 0.031); rs1353747 (PDE4D) and rs6472903 (8q21.11) with higher acini count per TDLU (P=0.007, 0.027); and rs1353747 (PDE4D) and rs204247 (RANBP9) with higher epithelial content (P=0.024, 0.017). Overall, breast cancer susceptibility SNPs showed limited enrichment for associations with TDLU involution.

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).

Large pooled case-control study of 49,608 breast cancer cases and 48,772 controls from 39 studies in the Breast Cancer Association Consortium independently confirmed four SNPs as breast cancer susceptibility loci. SNP rs614367 (CCND1 region) showed the strongest association (OR 1.21, P < 1×10⁻⁸) overall and OR 1.29 for hormone receptor-positive breast cancer. SNPs rs1011970 (CDKN2A/2B, OR 1.09), rs10995190 (ZNF365, OR 0.92), and rs704010 (ZMIZ1) were also significantly associated with breast cancer risk in women of European descent, while rs2380205 (10p15) showed limited evidence.