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.

BackgroundAlthough the etiology of women’s cancer has been extensively studied in the last few decades, there is still little evidence comparing the temporal pattern of these cancers among different populations.MethodsCancer incidence and mortality data from 1988 to 2015 were extracted from the Changle Cancer Register in China, and cancer incidence data for Los Angeles were extracted from Cancer Incidence in Five Continents plus database. A Joinpoint regression model was used to analyze the temporal trends of incidence and mortality for breast, cervical, corpus uteri and ovarian cancers. The standardized incidence ratios were applied to compare the cancer risk across populations.ResultsAn increasing trend of incidence rate for breast, cervical, corpus uteri and ovarian cancer was observed in Changle, although the rate leveled off for breast and cervical cancer after 2010, although not statistically significant. The mortality rate of breast and ovarian cancer was slightly increased during this period, while we found a decreased mortality of cervical cancer from 2010. The mortality of corpus uteri cancer showed a decreasing and then increasing trend. The incidence of breast, corpus uteri and ovarian cancer in Chinese American immigrants in Los Angeles was significantly higher than indigenous Changle Chinese and lower than Los Angeles whites. However, the incidence of cervical cancer in Chinese American immigrants shifted from significantly exceeding to lower than Changle Chinese.ConclusionThe incidence and mortality of women’s cancers in Changle were generally on the rise, and this study concluded that environmental changes were important factors affecting the occurrence of these cancers. Appropriate preventive measures should be taken to control the occurrence of women’s cancers by addressing different influencing factors.

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].

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 risk and survival were extracted from the recent genome-wide association study, with available survival information for 96,661 patients. We further tested the associations between the polygenetic risk score (PRS) for chemokines and breast cancer in the UK Biobank cohort using logistic regression models. The association between chemokine expression in tumors and breast cancer survival was analyzed in the TCGA cohort with Cox regression models. Results: Plasma CCL5 was causally associated with the risk of 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. In addition, we also found an inverse association between CCL19 expression in tumors and breast cancer overall and relapse-free survival (HR=0.58, 95% CI=0.35-0.95). Conclusion: We observed an inverse association between genetic predisposition to CCL5 and the risk of 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.