Mendelian randomization analyses of associations between breast cancer and bone mineral density

Abstract

The purpose of this study was to verify whether there is a causal relationship between breast cancer and bone mineral density (BMD). Summary statistics for exposures and outcomes were obtained from corresponding genome-wide association studies. The bidirectional and multivariate mediated Mendelian randomization (MR) analyses were performed. In the bidirectional MR analysis, breast cancer might reduce the BMD of the heel (HE-BMD) (FDR = 1.51 × 10−4) as might its ER+ subtype (FDR = 1.51 × 10−4). From BMD to breast cancer, no significant association was found (FDR > 0.05). The mediating MR analysis showed that Higher free testosterone (FT) only mediated the causal relationship between breast cancer and HE-BMD by 2.9%; both ER+ type and FT were independent factors of HE-BMD (ER+: P = 0.021; FT: P = 6.88 × 10−6). Higher FT could increase the risk of breast cancer (FDR = 1.21 × 10−3) as could total testosterone (TT) (FDR = 5.81 × 10−3). Similarly, higher FT could increase the risk of ER+ subtype (FDR = 2.51 × 10−6) as could TT (FDR = 5.55 × 10−4). These results indicate that BMD is not a risk factor for breast cancer but breast cancer and its ER+ subtype are risk factors for BMD loss. Furthermore, higher FT and TT levels are associated with both an increased incidence of breast cancer and increased bone density.

Causal relationships between circulating metabolites and rheumatoid arthritis: A mendelian randomization study

“…The weighted median approach was employed in instances where the MR analysis was influenced by a significant proportion of invalid instrumental variables contributing to half of the analysis weight [ 27 ]. We calculated F-statistics using the approximation method introduced by HongWu et al [ 28 ]. We defined IVs with F-statistics exceeding a threshold of 10 as valid for our analysis, ensuring a strong first-stage regression.…”

A causal relationship between bone mineral density and breast cancer risk: a Mendelian randomization study based on East Asian population

“…Furthermore, these observational studies cannot explain the causal relationship between the two. A Mendelian randomization study by Wu et al [15], based on individuals of European descent, suggested that BMD is not the risk factor for BC,rather ,BC can lead to decreased bone density. Most of the observational studies collected on the BMD and the risk of BC are based on European or Caucasian populations, while the incidence and mortality rates of BC vary signi cantly in different regions of the world [16].…”