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Introduction: Major depression disorder (MDD) has been associated with increased breast cancer risk in epidemiological studies; however, it is still unknown whether this association is causal or not. The aim of this study is to determine the causal relationship between MDD and breast cancer risk. Methods: Two‐sample Mendelian randomization (MR) analyses with 92 single‐nucleotide polymorphisms (SNPs) significantly associated with MDD as instrumental variables (IVs) were performed. Effects of these SNPs on breast cancer in women were estimated in the Breast Cancer Association Consortium (122,977 cases and 105,974 controls) using inverse variance weighted (IVW), weighted median and multivariable MR models. Heterogeneity and pleiotropy effects were assessed based on IVW and MR‐Egger regression model, respectively. Results: An 8.7% increased risk of overall breast cancer [odds ratio (OR) = 1.087; 95% confidence interval (CI) 1.011–1.170; P = 0.025] per log‐odds ratio increment of MDD risk based on the IVW model was noticed. Similar results were obtained with the multivariable MR model (OR = 1.118, 95% CI = 1.010–1.237; P = 0.031). An increment but not statistically significant causality association was noticed between MDD and risk of ER+ (OR = 1.098, 95% CI = 0.984–1.227; P = 0.093) or ER‐ (OR = 1.129, 95% CI = 0.982–1.297; P = 0.089) breast cancer under multivariable MR model. No significant pleiotropy effects were observed for the IVs in the two‐sample MR studies. Conclusions: The results suggested that a genetic predisposition of MDD is causally associated with overall breast cancer risk; however, the underlying biological mechanisms are worthy of further study. [ABSTRACT FROM AUTHOR]

The vitamin D receptor (VDR) principally mediates the anticancer activities of vitamin D. Various epidemiological studies have investigated the associations of VDR gene polymorphisms with ovarian cancer; however, the results have been inconclusive. In the current study, we evaluated, in a meta-analysis, the association of five common single nucleotide polymorphisms (SNPs) in the VDR gene (ApaI, BsmI, Cdx-2, FokI, and TaqI) with the risk of ovarian cancer. Six eligible studies, with a total of 4,107 cases and 6,661 controls, which evaluated the association of these variants and ovarian cancer risk, were identified from the MEDLINE and PubMed databases. The meta-analysis indicated that FokI was associated with an increased ovarian cancer risk, with a pooled odds ratio (OR) of 1.10 [95% confidence intervals (95% CI) = 1.00–1.20] for CT heterozygotes and 1.16 (95% CI = 1.02–1.30) for TT homozygotes relative to common CC carriers. Carriers of the T allele (also known as the f allele) showed an 11% (pooled OR = 1.11, 95% CI = 1.02–1.21; TT/CT vs. CC) increased risk of ovarian cancer relative to CC carriers. For FokI, no significant heterogeneity between the studies was found (I2 = 0%, P = 0.62 for the Q test). There was no statistically significant association between the other four variants (ApaI, BsmI, Cdx-2 and TaqI) and risk of ovarian cancer. These data indicate that the polymorphism FokI on the VDR is a susceptibility factor for ovarian cancer. Nevertheless, more studies are warranted to elucidate the underlying mechanisms of the VDR in development of ovarian cancer. [ABSTRACT FROM AUTHOR]