Background: Despite the potential role of several chemokines in the migration of cytotoxic immune cells to prohibit breast cancer cell proliferation, a comprehensive view of chemokines and the risk and prognosis of breast cancer is scarce, and little is known about their causal associations.Methods: With a two-sample Mendelian randomization (MR) approach, genetic instruments associated with 30 plasma chemokines were created. Their genetic associations with breast cancer and its survival by molecular subtypes were extracted from the recent genome-wide association study of 133,384 breast cancer cases and 113,789 controls, with available survival information for 96,661 patients. We further tested the associations between the polygenic risk score (PRS) for chemokines and breast cancer in the UK Biobank cohort using logistic regression models, while the association with breast cancer survival was tested using Cox regression models. In addition, the association between chemokine expression in tumors and breast cancer survival was also analyzed in the TCGA cohort using Cox regression models.Results: Plasma CCL5 was causally associated with breast cancer in the MR analysis, which was significant in the luminal and HER-2 enriched subtypes and further confirmed using PRS analysis (OR = 0.94, 95% CI = 0.89–1.00). A potential causal association with breast cancer survival was only found for plasma CCL19, especially for ER-positive patients. Although not replicated in the UK Biobank, we still found an inverse association between CCL19 expression in tumors and breast cancer overall and relapse-free survival in the TCGA cohort (HR = 0.58, 95% CI = 0.35–0.95).Conclusion: We observed an inverse association between genetic predisposition to CCL5 and breast cancer, while CCL19 was associated with breast cancer survival. These associations suggested the potential of these chemokines as tools for breast cancer prevention and treatment.

Background Despite the known increasing incidence of breast cancer in China, evidence on the spatial pattern of hospitalization for breast cancer is scarce. This study aimed to describe the disparity of breast cancer hospitalization in the rural population of Southeast China and to explore the impacts of socioeconomic factors and heavy metal pollution in soil. Methods This study was conducted using the New Rural Cooperative Medical Scheme (NRCMS) claims data covering 20.9 million rural residents from 73 counties in Southeast China during 2015–2016. The associations between breast cancer hospitalization and socioeconomic factors and soil heavy metal pollutants were evaluated with quasi-Poisson regression models and geographically weighted Poisson regressions (GWPR). Results The annual hospitalization rate for breast cancer was 101.40/100,000 in the studied area and the rate varied across different counties. Overall, hospitalization for breast cancer was associated with road density (β = 0.43, P = 0.02), urbanization (β = 0.02, P = 0.002) and soil cadmium (Cd) pollution (β = 0.01, P = 0.02). In the GWPR model, a stronger spatial association of Cd, road density and breast cancer hospitalization was found in the northeast regions of the study area while breast cancer hospitalization was mainly related to urbanization in the western regions. Conclusions Soil Cd pollution, road density, and urbanization were associated with breast cancer hospitalization in different regions. Findings in this study might provide valuable information for healthcare policies and intervention strategies for breast cancer.

Background Despite the known increasing incidence of breast cancer in China, evidence on the spatial pattern of hospitalization for breast cancer is scarce. This study aimed to describe the disparity of breast cancer hospitalization in Southeast China and to explore the impacts from socioeconomic factors and heavy metal pollution in soil. Methods This study was conducted using the New Rural Cooperative Medical Scheme (NRCMS) claims data covering 25.52 million female rural residents from 73 counties in Southeast China during 2015–2016. The associations between breast cancer hospitalization and socioeconomic factors and soil heavy metals pollutants were evaluated with quasi-Poisson regression models and geographically weighted Poisson regressions (GWPR). Results The annual hospitalization rate for breast cancer was 101.40/100,000 in the studied area and the rate varied across different counties. Overall, hospitalization for breast cancer was associated with road density (β = 0.43, P = 0.02), urbanization (β = 0.02, P = 0.002) and soil cadmium (Cd) pollution (β = 0.01, P = 0.02). In the GWPR model, a stronger spatial association of Cd, road density and breast cancer hospitalization was found in the northeast regions of the study area while breast cancer hospitalization was mainly related to urbanization in the western regions. Conclusions Soil Cd pollution, road density, and urbanization were associated with breast cancer hospitalization in different regions. Findings in this study might provide valuable information for healthcare policies and intervention strategies for breast cancer.

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Background: Processed meat and alcohol have been consistently associated with breast cancer risk, but evidence for their effects in women with different genetic susceptibility of breast cancer is scarce, and little is known about their interactions.<br /><br />Methods: We analyzed data from 260,779 female participants in the UK Biobank. Multivariable adjusted Cox proportional hazards models were used to estimate hazard ratios (HR) and 95% confidence intervals (CI) for associations between processed meat and breast cancer risk. We further assessed its interaction with alcohol intake and polygenic risk score (PRS) for breast cancer.<br /><br />Results: Processed meat intake more than once a week was positively associated with risk of breast cancer, especially in women took alcohol ≥1/d (HR=1.50, 95% CI=1.17-1.93), and in women who usually took alcohol together with meals (HR=1.70, 95% CI=1.21-2.39, P for interaction=0.048). The association between processed meat and breast cancer did not differ by menopausal status. When further stratified by PRS, processed meat more than once a week intake was associated with risk of breast cancer (HR=1.17, 95% CI=1.02-1.35) in women with the highest quantile of PRS, and additive interaction was found between them.<br /><br />Conclusion: Processed meat was associated with risk of breast cancer in women, and the effect was stronger in those who took alcohol together with the meal and with high PRS of breast cancer, suggesting the focus of future preventive measures on these women.<br /> Funding: This work was supported by the Natural Science Foundation of Fujian Province [grant no: 2021J01721], the Startup Fund for High-level Talents of Fujian Medical University [grant no: XRCZX2020007], Startup Fund for Scientific Research, Fujian Medical University [grant no: 2019QH1002] and Laboratory Construction Program of Fujian Medical University [grant no: 1100160208].