By Vijay Kumar MalesuNov 7 2023Reviewed by Danielle Ellis, B.Sc.

In a recent study published in JAMA Network Open, researchers investigated the association between neighborhood deprivation and alterations in deoxyribonucleic acid (DNA) methylation and gene expression in breast cancer tissues of Black and White women.

Study: Neighborhood Deprivation and DNA Methylation and Expression of Cancer Genes in Breast Tumors. Image Credit: Photoroyalty/Shutterstock.com

Background 

Despite advances in breast cancer treatment reducing mortality across all racial and ethnic groups, Black women face a 40% higher death rate than White women. Socioeconomic disparities, notably in underprivileged neighborhoods, are correlated with poorer health outcomes and higher cancer rates.

Research suggests a link between such deprivation and DNA methylation changes, affecting gene regulation and potentially influencing breast cancer progression.

Despite a decrease in overall breast cancer mortality, disparities, especially between Black and White women, persist, indicating that further research is necessary to guide interventions and policies aimed at addressing health inequalities.

About the study 

In this present cross-sectional study, researchers collected a convenience sample of breast tumor tissue from 185 women—110 Black and 75 White—who underwent surgery at the University of Maryland Medical Center and other hospitals in the Baltimore area.

These women were part of a larger cohort of 456 patients who participated in the National Cancer Institute-Maryland Breast Cancer Study, which adheres to the Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) guidelines. The study's protocol received approval from relevant institutional review boards, and all women gave written informed consent and answered a questionnaire.

The participants' addresses were geocoded and linked to the 2000 census data to assess neighborhood deprivation using an index that consolidated multiple socioeconomic variables into a single score. The researchers evaluated the Neighborhood Deprivation Index (NDI), which uses six indicators to assess factors such as poverty and unemployment; higher NDI scores denote increased deprivation. 

To investigate DNA methylation in breast tumor tissues, they employed the Infinium MethylationEPIC 850K BeadChip, precisely measuring methylation at CpG sites. The resulting data underwent rigorous quality control and normalization processes using the DNAmArray package and other statistical tools in R. Probes with low success rates, single-nucleotide variants, or nonspecific results were excluded, leading to a final set of 750,426 probes for the study.

Additionally, they analyzed immune cell variations within tumors using methylCIBERSORT deconvolution with the normalized data. They applied rigorous statistical methods, maintaining traditional p-value significance levels and adjusting for multiple comparisons. Their models also examined the relationship between NDI and methylation, considering age, race, and tumor purity. Conducted over nine months in 2022, this comprehensive analysis utilized statistical software such as Stata, JMP, and R. 

Study results 

The present study investigated 185 women with breast cancer from Baltimore, Maryland, differentiated by their neighborhood's deprivation status. The sample primarily consisted of Black women (59.5%) and those with a high school education (48.6%), with most having a household income at or below $60,000 (79.5%).

At the time of their surgery, the average age was 56 years and the data, including missing information, was organized by neighborhood status and indicated higher deprivation among Black participants, lower-income earners, and those unmarried or no longer in a marriage.

An analysis of neighborhood deprivation in relation to race revealed a significant disparity, with Black women residing in more deprived neighborhoods than White women. The distribution of breast cancer subtypes across different levels of neighborhood deprivation showed an inconclusive higher presence of triple-negative breast cancer in highly deprived areas.

Further, the study explored the impact of neighborhood deprivation on DNA methylation, particularly at 8 CpG sites after adjustments for age, tumor purity, and methylation batch, revealing associations with neighborhood deprivation.

Two sites in tumor suppressor genes, LRIG1 and WWOX, were of note and re-ribonucleic acid (reRNA) sequencing data available for some patients showed that high deprivation correlated with lower expression of these genes. Specifically, the methylation status in LRIG1's promoter and gene body regions was inversely related to its transcript levels.

The analysis then refined in on the LRIG1 and WWOX genes among Black patients, and a negative correlation was found between LRIG1 methylation and neighborhood deprivation, an association not seen in White patients. Similarly, LRIG1's expression dipped with increasing deprivation, but only among Black women.

The KMplotter tool revealed an inverse relationship between LRIG1 expression and improved outcomes for recurrence-free and overall survival, notably in estrogen receptor-positive tumors or post-surgery treatment recipients, a finding that was confirmed by additional datasets.

The WWOX gene's expression was also inversely related to neighborhood deprivation in Black patients only. However, no other significant associations surfaced for WWOX. Additionally, the study used methylCIBERSORT for estimating immune cell population differences in tumor tissues by neighborhood deprivation. The analysis indicated a decrease in the relative proportion of neutrophils in patients from high deprivation areas, after controlling for age and race.

Journal reference:

Brittany D. Jenkins, Emily Rossi, Catherine Pichardo, et al.  Neighborhood Deprivation and DNA Methylation and Expression of Cancer Genes in Breast Tumors. JAMA Network Open, 2023. doi: 10.1001/jamanetworkopen.2023.41651 https://jamanetwork.com/journals/jamanetworkopen/fullarticle/2811393?utm_campaign=articlePDF&utm_medium=articlePDFlink&utm_source=articlePDF&utm_content=jamanetworkopen.2023.41651