Metabolic Signatures and Genetic Factors
New research has shed light on a crucial aspect of breast cancer, particularly in African American women, and the intriguing metabolic disparities it exhibits. This groundbreaking study, recently published in Nature Scientific Reports, delves into the intricate world of estrogen receptor-positive (ER-positive) breast cancer, unraveling distinctive metabolic signatures within the blood of African American women compared to non-Hispanic white women. Furthermore, it identifies a pivotal player in this complex scenario: negative elongation factor complex E (NELFE), associated with higher mortality rates among African American women battling ER-positive breast cancer.
Understanding the Research
ER-positive breast cancer represents the most prevalent form, accounting for 70%-80% of all breast cancer cases. Astonishingly, African American women face a 40% higher risk of mortality from this type of cancer compared to their white counterparts. Zeynep Madak-Erdogan, a professor at the University of Illinois Urbana-Champaign and co-author of the study, underscores this alarming statistic. She emphasizes that, despite advancements in early diagnosis and treatment, patients from lower-income neighborhoods, such as Chicago’s South Side, tend to experience poorer outcomes. This observation suggests the existence of biological factors contributing to these disparities.
The study’s diverse participant pool included African American and non-Hispanic white women aged 20-79, recruited from three hospitals in the Chicago area during 2018-19. Blood samples were collected from 102 newly diagnosed ER-positive breast cancer patients (in stages 1-3), while 148 healthy women served as the control group. Importantly, the control group participants were meticulously matched based on various factors, including tumor types and economic backgrounds, enabling a comprehensive examination of neighborhood effects.
Metabolic Clues and Genetic Insights
The research team scrutinized 83 metabolites in the participants’ blood samples, revealing intriguing distinctions. African American women with ER-positive breast cancer exhibited decreased levels of circulating amino acids, including the antioxidant methionine, compared to the healthy control group. Conversely, non-Hispanic white patients with the disease displayed significantly higher levels of fatty acids than both African American women and those in the healthy control group.
The hypothesis arises that African American patients may require greater methionine levels to support increased DNA methylation, a mechanism governing gene expression. Hypermethylation, an aberrant process in DNA, may explain the poorer disease outcomes experienced by African American women. It can silence the expression of cancer-related genes, including tumor suppressors.
Utilizing the Pan-Cancer Atlas database, the research team mapped the metabolites to epigenetic regulatory systems. They identified 291 genes associated with methylation activities expressed at higher rates, 15 of which were statistically significant, in African American women with ER-positive breast cancer.
Crucially, the study revealed that poorer survival rates among African American women were linked to higher expression of the NELFE gene, a protein complex regulating enzymes involved in transcriptional activities for downstream target genes.
Tumor cells employ amino acids as alternative fuels and precursors for essential processes, such as DNA synthesis and the promotion of rapid growth and proliferation. Previous research by Madak-Erdogan’s group had already identified how higher levels of free fatty acids can rewire cancer cell metabolism, facilitating tumor growth and proliferation in obesity-related cancers. This study extends this work by demonstrating key differences by race: While higher fatty acid levels serve as reliable predictors of ER-positive breast cancer in non-Hispanic white women, elevated amino acid levels are more indicative of the disease in African American women.
The implications of these metabolic distinctions are profound, suggesting the potential for different screening strategies tailored to identify varying breast cancer types. If a cost-effective blood test could be developed to diagnose breast cancers earlier, especially those with worse prognoses, it could be a game-changer, particularly in resource-constrained healthcare settings. Currently, the gold standard for screening is mammography, which requires specialized equipment and trained professionals.
This research opens new avenues for understanding the metabolic intricacies of ER-positive breast cancer in African American women. It underscores the importance of considering genetic and metabolic factors in the quest for more effective diagnostic and treatment strategies, ultimately striving for equitable outcomes in the battle against breast cancer.
