Contributions of selenoproteins to breast cancer etiology and racial disparity

TL;DR

This study explores how selenoproteins and their regulators may contribute to breast cancer and racial disparities in outcomes.

Contribution

The study identifies racial differences in selenoprotein expression and genetic variation in breast cancer tissues.

Findings

SELENOF and eIF4a3 levels were elevated in breast cancer tissues.

SELENOP genotypes showed age-related differences and were associated with breast cancer.

African American women had higher SELENOF/eIF4a3 levels and a specific SELENOP polymorphism.

Abstract

Breast cancer etiology is multifactorial with African American women experiencing a significant health disparity in clinical presentation and outcomes. The selenium-containing protein SELENOF has been implicated in breast carcinogenesis by cell culture and animal studies. SELENOF translation is highly regulated in part by the RNA helicase eIF4a3, which binds to the key regulatory regions in the SELENOF mRNA and suppress its translation. In addition, SELENOP, the primary selenium transporter, plays a critical role in selenium delivery to tissues and may influence selenoprotein synthesis. This study aimed to examine the levels of SELENOF and eIF4a3, along with SELENOF and SELENOP genotypes, in breast cancer tissues from African American and Caucasian women

To study their roles in breast cancer outcome and racial disparity, human tissues were assessed by multiplex immunofluorescence staining with antibodies directed against SELENOF and eIF4a3 and DNA from these tissues were genotyped for previously studied variations in SELENOF and the selenium transporter protein SELENOP

Elevated levels of both SELENOF and eIF4a3 were observed in breast cancer tissues. SELENOF expression and genotype varied by HER2 status, while SELENOP genotypes were associated with breast cancer and showed age-related differences. SELENOF and eIF4a3 were also higher in tissues derived from African American women, who also exhibited higher frequency of a SELENOP polymorphism in the non-coding region of the gene

These findings suggest that SELENOF, eIF4a3, and SELENOP may contribute to breast cancer progression and racial disparities in outcomes. Their differential expression and genetic variation highlight potential molecular mechanisms underlying these disparities and may inform future therapeutic or diagnostic strategies.

The online version contains supplementary material available at 10.1007/s10552-025-02123-y.

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