Background Both depression and breast cancer (BC) contribute to a substantial global burden of morbidity and mortality among women, and previous studies have observed a potential depression-BC link. We aimed to comprehensively characterize the phenotypic and genetic relationships between depression and BC. Methods We first evaluated phenotypic association using longitudinal follow-up data from the UK Biobank (N = 250,294). We then investigated genetic relationships leveraging summary statistics from the hitherto largest genome-wide association study of European individuals conducted for depression (N = 500,199), BC (N = 247,173), and its subtypes based on the status of estrogen receptor (ER + : N = 175,475; ER − : N = 127,442). Results Observational analysis suggested an increased hazard of BC in depression patients (HR = 1.10, 95%CIs = 0.95–1.26). A positive genetic correlation between depression and overall BC was observed ($${r}_{g}$$ r g = 0.08, P = 3.00 × 10–4), consistent across ER + ($${r}_{g}$$ r g = 0.06, P = 6.30 × 10–3) and ER − subtypes ($${r}_{g}$$ r g = 0.08, P = 7.20 × 10–3). Several specific genomic regions showed evidence of local genetic correlation, including one locus at 9q31.2, and four loci at, or close, to 6p22.1. Cross-trait meta-analysis identified 17 pleiotropic loci shared between depression and BC. TWAS analysis revealed five shared genes. Bi-directional Mendelian randomization suggested risk of depression was causally associated with risk of overall BC (OR = 1.12, 95%Cis = 1.04–1.19), but risk of BC was not causally associated with risk of depression. Conclusions Our work demonstrates a shared genetic basis, pleiotropic loci, and a putative causal relationship between depression and BC, highlighting a biological link underlying the observed phenotypic relationship; these findings may provide important implications for future studies aimed reducing BC risk.

IntroductionSince 2006, the human papillomavirus (HPV) vaccine has been recommended for females aged 9–26 years in the United States. Aiming to evaluate the early effect of the HPV vaccine on cervical cancer, this study assessed the incidence of cervical cancer by age and histology before and after the introduction of HPV vaccination.MethodsData on cervical cancer incidence from 1975–2019 were extracted from the Surveillance, Epidemiology, and End Results Program. Joinpoint regression was used to determine temporal trends over time. Future cervical cancer incidence (2015–2039) was projected using Bayesian age-period-cohort analysis. Age-period-cohort (APC) models were created to evaluate age, period, and cohort effects.ResultsFor overall cervical cancer and cervical squamous cell carcinoma (SCC), incidence rate showed decreasing trends (–0.7%, and –1.0% annually, respectively), whereas cervical adenocarcinoma (AC) incidence continuously increased (2.6% annually). The incidence trends for AC were stable in the 20–24 and 25–29-year age groups, whereas there was an increasing trend in older age groups. Similarly, the projected trend for AC in females aged 20–30 years exhibited a decline, whereas an increase was predicted in the 31–40–year age group, especially in the 35–44 year age group. The birth cohort and period effects in SCC and AC were extracted from APC models.DiscussionDuring the period of 1975–2019, the incidence of cervical AC remained almost unchanged in the age groups receiving HPV vaccines while increased in the age groups not receiving HPV vaccines. The birth cohort effects of SCC and AC of the cervix provided evidence supporting the effectiveness of the HPV vaccine in preventing cervical cancer.

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