Researcher analyzes molecular changes for clues about disparities in breast cancer outcomes

Spread the love

It is a figure that stands out. Black women have a 36% higher breast cancer mortality rate than other races, despite having a similar incidence to white women. Black women are also more likely to be diagnosed with breast cancer at a younger age than white women and have twice the rate of aggressive and more difficult-to-treat triple-negative breast cancer.

There is an ongoing debate about how much of these disparities is due to social determinants of health, such as access to health care, and how much is caused by biology, says MUSC Hollings Cancer Center researcher Peggi Angel, Ph. d One hypothesis is that chronic social and economic stressors result in ancestry-dependent molecular changes that create a tumor-permissive tissue microenvironment in normal breast tissue, she said, citing findings from a recent study her team published. in Frontiers in Oncology

Angel, an analytical chemist by training, is interested in what happens at the molecular level. Her recent study with her graduate student Denys Rujchanarong looked at normal breast tissue labeled as being at risk for breast cancer, according to the Gail Model, which assigns an estimated breast cancer risk based on personal factors, such as age, age at the onset of menstruation and age at birth of the first child, and saw associations between socioeconomic stressors and specific patterns of N-glycosylation in black and white women.

N-glycosylation is a metabolic process of creating a sugar modification in a protein structure. The research was an initial step in linking molecular markers to socioeconomic stress, Angel said.

“We tried to look at differences in social status between black women and white women and compare that to molecular factors that might be predictive,” she said. “I think this is a much-needed area of ​​research because it’s really complicated and there are clearly some molecular changes that could be related to geographic origin.”

He noted that it’s important to start looking at differences in breast tissue before cancer develops.

“Differences in initial glycosylation in normal breast tissue may be contributing to specific differences in mammary stromal biology that disproportionately affect black women,” the article reported.

Angel’s team obtained donated normal breast tissue samples from black and white women from the Susan G. Komen for the Cure Tissue Bank. The two groups were compared for age, body mass index, education level, Gail score, family income, and marital status. Using mass spectrometry, the distribution of N-glycans in the tissues was evaluated, leading to the identification of 53 N-glycans. From there, the N-glycans were associated with specific socioeconomic factors.

Results from these samples, which included tissue from 30 white women and 30 black women, pointed to metabolic patterns linked to socioeconomic stressors as a potential factor in breast cancer disparities between black and white women.

This study could also be the first to look at the spatial distribution of fucosylation structures in normal breast tissue, Angel said. Fucosylation is a modification of glycosylation that has been observed at elevated levels in malignant transformations in breast, liver, pancreatic, prostate, and colorectal cancers.

The study cited that, based on current literature and the team’s findings, it is possible that in normal tissue, changes in fucose patterns may be contributing to a tumor-friendly microenvironment associated with more severe, protein-influenced breast cancers. genetic ancestry and BMI (body mass index). ).

Angel said they have found that post-translational modifications called glycosylation (sugar residues added to proteins) vary by BMI in the normal breast defined by ancestry. Body weight is an important measurement to track, as current statistics show that black women in the US have higher rates of BMIs that fall into the overweight or obese categories compared to white women.

BMI and weight gain have been recognized as a major risk factor for breast cancer, Angel said, citing a study that found an 11-pound increase in BMI corresponded to a 2% increase in risk of breast cancer. Studies have linked obesity to a higher incidence of a specific and more aggressive type of breast cancer, triple-negative breast cancer, in black women. So not only do black women experience an uneven burden of obesity, they are also being diagnosed with breast cancer at younger ages and with higher rates of aggressive breast cancers compared to their white counterparts, she noted.

Angel said it is vitally important to continue investigating the spatial distribution of collagen protein types and post-translational modifications to better understand the impact that socioeconomic status has on the specific biological factors, processes, and modifications that contribute to the development of diseases such as breast cancer

BMI is only part of the picture. The results of her team’s study suggest that from a subset of N-glycans significantly altered by ancestry, certain N-glycans were strongly associated with family income for white women, while the same N-glycans were strongly associated. with the marital status of black women.

This may imply that immune responses triggered by specific lifestyle stressors are different for black and white women and that future studies should look at glycosylation changes associated with immune components, a promising area of ​​research linking markers molecular relationships with socioeconomic stress. However, more research is needed to identify specific N-glycan biomarkers associated with socioeconomic stresses, such as family income and marriage, to determine which glycan signatures are associated with increased breast cancer risk, he said in the study. .

“This furthers our understanding of glycosylation regulation and the possibility that such regulation may be influenced by socioeconomic stressors. To our knowledge, this is the first study to investigate patterns of N-glycans associated with socioeconomic stress that may differ by ancestry.This is important because it contributes to understanding the complexities that link socioeconomic stresses and molecular factors with breast cancer risk and aggressiveness in black women.Additional factors to consider include disposable income, family size, childhood socioeconomic status and educational quality, as these are factors that may also play a role in the continuing health disparities faced by black women.”

Ángel said that the research is at an important moment, since he has developed an approach that allows his team to define the structure of the collagen protein spatially within the microenvironment of the tissue. This allows them to investigate not only where collagen structure is changed after translation, but also the location and cell types and expression associated with that change.

The goal is for researchers to use the molecular signatures to develop more specific diagnoses of breast cancer, including, perhaps, subtypes of breast cancer. Additionally, being more specific in defining collagen structure can help them determine biomarkers and develop more targeted therapies.

“The gap in mortality disparities for black women from breast cancer is an urgent problem that must be addressed,” he said. “I hope we can discover the molecular signatures that form tumor-permissive breast density and develop therapeutic approaches that can reverse this change.”

#Researcher #analyzes #molecular #clues #disparities #breast #cancer #outcomes

Leave a Comment

Your email address will not be published.