A fundamental objective of public health is to identify the causes of diseases and associated risk factors to develop effective prevention strategies. In this regard, the population attributable fraction (PAF) has become a key epidemiological measure for quantifying the proportion of disease incidence in a population attributable to specific risk factors.Current Concepts: The concept of PAF is widely applied in epidemiological and public health research, playing a crucial role in prioritizing disease prevention and management strategies. Estimating the PAF of cancer risk factors based on national data provides essential evidence for the formulation of government-led cancer control policies and prevention strategies. In particular, these estimates serve as critical indicators for evaluating cancer control programs and informing policy decisions. Given the variations in risk factor prevalence across different populations, it is crucial to estimate PAF using country-specific data to ensure the development of tailored and effective public health interventions.Discussion and Conclusion: This study underscores the importance of PAF as a foundational tool for evidencebased policymaking and highlights the need for periodic reassessment to enhance the effectiveness of cancer prevention and control efforts.

Triple-negative breast cancer (TNBC) is a subtype of breast cancer that lacks hormone receptor and Her2 (ERBB2) expression, leaving chemotherapy as the only treatment option. The urgent need for targeted therapy for TNBC patients has led to the investigation of small interfering RNAs (siRNAs), which can target genes in a sequence-specific manner, unlike other drugs. However, the clinical translation of siRNAs has been hindered by the lack of an effective delivery system, except in the case of liver diseases. The MYC oncogene is commonly overexpressed in TNBC compared to other breast cancer subtypes. In this study, we used siRNA to target MYC in MDA-MB-231, MDA-MB-157, MDA-MB-436 and Hs-578T cells. We designed various symmetric and asymmetric (asiRNAs), screened them for in vitro efficacy, modified them for enhanced nuclease resistance and reduced off-target effects, and conjugated them with cholesterol (ChoL) and docosanoic acid (DCA) as a delivery system. DCA was conjugated to the 3’ end of asiRNA by a cleavable phosphodiester linker for in vivo delivery. Our findings demonstrated that asiRNA-VP and Mod_asiRNA10-6 efficiently downregulated MYC and its downstream targets, including RRM2, RAD51 and PARP1. Moreover, in a tumor xenograft model, asiRNA-VP-DCA effectively knocked down MYC mRNA and protein expression. Remarkably, durable knockdown persisted for at least 46 days postdosing in mouse tumor xenografts, with no visible signs of toxicity, underscoring the safety of DCA-conjugated asiRNAs. In conclusion, this study developed novel asiRNAs, design platforms, validated modification patterns, and in vivo, delivery systems specifically targeting MYC in TNBC.

Triple-negative breast cancer (TNBC) is a subtype of breast cancer that lacks hormone receptor and Her2 (ERBB2) expression, leaving chemotherapy as the only treatment option. The urgent need for targeted therapy for TNBC patients has led to the investigation of small interfering RNAs (siRNAs), which can target genes in a sequence-specific manner, unlike other drugs. However, the clinical translation of siRNAs has been hindered by the lack of an effective delivery system, except in the case of liver diseases. The MYC oncogene is commonly overexpressed in TNBC compared to other breast cancer subtypes. In this study, we used siRNA to target MYC in MDA-MB-231, MDA-MB-157, MDA-MB-436 and Hs-578T cells. We designed various symmetric and asymmetric (asiRNAs), screened them for in vitro efficacy, modified them for enhanced nuclease resistance and reduced off-target effects, and conjugated them with cholesterol (ChoL) and docosanoic acid (DCA) as a delivery system. DCA was conjugated to the 3’ end of asiRNA by a cleavable phosphodiester linker for in vivo delivery. Our findings demonstrated that asiRNA-VP and Mod_asiRNA10-6 efficiently downregulated MYC and its downstream targets, including RRM2, RAD51 and PARP1. Moreover, in a tumor xenograft model, asiRNA-VP-DCA effectively knocked down MYC mRNA and protein expression. Remarkably, durable knockdown persisted for at least 46 days postdosing in mouse tumor xenografts, with no visible signs of toxicity, underscoring the safety of DCA-conjugated asiRNAs. In conclusion, this study developed novel asiRNAs, design platforms, validated modification patterns, and in vivo, delivery systems specifically targeting MYC in TNBC.

A fundamental objective of public health is to identify the causes of diseases and associated risk factors to develop effective prevention strategies. In this regard, the population attributable fraction (PAF) has become a key epidemiological measure for quantifying the proportion of disease incidence in a population attributable to specific risk factors.Current Concepts: The concept of PAF is widely applied in epidemiological and public health research, playing a crucial role in prioritizing disease prevention and management strategies. Estimating the PAF of cancer risk factors based on national data provides essential evidence for the formulation of government-led cancer control policies and prevention strategies. In particular, these estimates serve as critical indicators for evaluating cancer control programs and informing policy decisions. Given the variations in risk factor prevalence across different populations, it is crucial to estimate PAF using country-specific data to ensure the development of tailored and effective public health interventions.Discussion and Conclusion: This study underscores the importance of PAF as a foundational tool for evidencebased policymaking and highlights the need for periodic reassessment to enhance the effectiveness of cancer prevention and control efforts.