Tampon Use in Adolescence: Differences among European American, African American and Latina Women in Practices, Concerns, and Barriers

Background. There is evidence to suggest that early life exposures including birthweight, history of having been breastfed during infancy, in utero exposure to maternal smoking, and parental education are associated with BC risk. Potential underlying mechanisms include variability in exposure to maternal endogenous sex and growth hormones. Also, parental socioeconomic status may be a proxy for environmental characteristics that impact biological processes in early life, and ultimately influence BC risk. Research has focused on EA women; relatively little is known about associations between early life exposures and BC risk for AA women. Methods. We conducted a case-control study in AA and EA women aged 22-75 years living in metropolitan New York City and eastern New Jersey (Women's Circle of Health Study). Breast cancer cases (AA n=827; EA n=772) were diagnosed with primary, incident, histologically confirmed invasive BC or ductal carcinoma in situ. Controls (AA n=905; EA n=715) were frequency matched to cases on age and race. Birthweight, history of having been breastfed during infancy, history of in utero exposure to maternal smoking, and parental education were by self-report using an interviewer-administered questionnaire. Results. Birthweight was not significantly associated with BC risk in this study for AA or EA women. Having been breastfed during infancy was associated with significantly increased BC risk for both groups (ORAA=1.60, 95% Cl: 1.27-2.02; OREA=1.45, 95% Cl: 1.14-1.85). For EA women, but not AA women, reporting in utero exposure to maternal smoking was associated with significantly decreased BC risk (OR=0.61, 95% Cl: 0.45-0.82). Among AA women, those born to mothers with at least a college degree had a significantly lower BC risk compared to AA women born to mothers with a high school or less education (OR=0.67, 95% Cl: 0.49-0.93). Among EA women, we found no association with maternal education. However, EA women born to fathers with at least a college degree had a significantly lower BC risk compared to EA women born to fathers with a high school or less education (OR=0.65, 95% Cl: 0.51-0.84). Conclusions. Our findings support the hypothesis that early life exposures impact adult BC risk. History of having been breastfed during infancy, in utero exposure to maternal smoking, and parental education were all associated with BC risk. While minor differences in risk estimates were found between EA and AA women, associations were similar. Citation Format: Mark L. Glasgow, Jo Freudenheim, Gary Zirpoli, Elisa Bandera, Christine Ambrosone. Early life exposures and breast cancer (BC) risk among African American (AA) and European American (EA) women. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr LB-13. doi:10.1158/1538-7445.AM2013-LB-13

Background: Human endogenous retroviruses (HERVs) are remnants of ancient virus infection. The majority of them are disabled due to mutation and/or deletion. However, HERV K113 and K115 have been shown to have full-length insertion in human genome and retain the ability to encode functional virus proteins in some individuals. Considering the potential role of HERVs in carcinogenesis and a high genetic homology between HERV K and mouse mammary tumor virus, the study is designed to investigate the distribution of HERV K113 and K115 in African American (AA) and European American (EA) women, and their association with breast cancer risk. Methods: Built on a funded multi-center case-control study, the Women's Circle of Health Study, the study included 1242 cases (608 AA and 634 EA) and 1422 controls (783 AA and 639 EA). PCR followed by fragment analysis was used for insertional polymorphism assay. For each HERV, three PCRs were performed to determine whether the insertion is partial or full length. Indeed, a subset of individuals showed insertion of long terminal repeat (LTR) of HERV, instead of whole virus insertion. The distribution of insertional polymorphisms was compared between AA and EA as well as between cases and controls. Logistic regression was used to calculate odds ratio (OR) and 95% confidence interval (CI) with adjustment for age at diagnosis and proportion of European ancestry. Results: For both K113 and K115, with or without including LTR insertion, the distribution was significantly different between AA and EA women. A two-fold higher prevalence of HERVs was observed in AA women, showing 51.5% of individuals with at least one copy of either K113 or K115 compared to 23.3% in EA women among controls. The prevalence of HERVs was inversely associated with proportions of European ancestry, showing a decrease from averagely 66% European ancestry in individuals without insertion to 42.9%, 23.2%, 13.3% with one, two, or more insertions of HERV K113 or K115, respectively. Between cases and controls, the prevalence of K113 was slightly higher in controls, but not for K115. Furthermore, both K113 and K115 insertion were significantly associated with the reduced risk of breast cancer in both AA and EA women. Near 50% reduction of breast cancer risk was observed in AA and EA women with homozygous insertion of K113 (combined OR, 0.45; 95% CI, 0.25-0.80). A trend of a reduction in breast cancer risk with an increase of copy number of HERV K insertion was observed in both AA and EA women. However, there was no association with breast cancer subtypes. Conclusion: This is the first study to document the prevalence of HERV K113 and K115 in AA and EA population, and to report an inverse association with breast cancer risk. Validation of the findings in a relatively large study is warranted in the future. Funded by 5R03CA156645, K07CA148888, P01151135, and R01CA100598. Citation Format: Li Tang, Steven R. Gregory, David Tritchler, Gary R. Zirpoli, Song Yao, Warren Davis, Gregory L. Ciupak, Yasmin Thanavala, Elisa V. Bandera, Christine B. Ambrosone. Associations between insertional polymorphisms of human endogenous retrovirus K113 and K115 and breast cancer risk in African American and European American women. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 2789. doi:10.1158/1538-7445.AM2015-2789

Ovarian cancer accounts for 5% of cancer deaths and is the fifth leading cause of cancer death in women in the United States. While incidence is higher in European American (EA) than African American (AA) women, five-year survival is worse for AA women (36%) than EA women (44%). Access to appropriate surgery and treatment is a major contributor but does not completely explain this disparity. The Cancer Genome Atlas (TCGA) identified four gene expression-based subtypes of the most common and lethal histotype, high grade serous carcinoma (HGSC): mesenchymal, proliferative, differentiated, and immunoreactive. We sought to characterize similarities and differences in gene expression-based subtypes arising in AA and EA women to determine whether there are underlying biologic features that may influence survival. We performed two distinct analyses, first using TCGA data and second using cases from the population-based African American Cancer Epidemiology Study (AACES). For both we summarized differential expression patterns for each subtype with moderated t statistic vectors for >10,000 genes using Significance Analysis of Microarrays. We calculated Pearson's correlations of these vectors to determine concordance of expression patterns between subtypes across EA and AA women. In TCGA, we observed correlations of subtype-specific expression patterns between the 24 AA and 475 EA tumors of 0.52-0.60 for each of the four subtypes. Thus, while analogous subtypes can be identified in AA and EA women, the magnitude of these correlations suggests that there are potential differences in gene expression patterns between AA and EA tumors that are assigned to the same subtype. We generated additional data from 58 AACES HGSC cases using the Affymetrix Human Transcriptome Array 2.0. Instead of assigning these tumors to previously-defined subtypes, we clustered samples to identify four subtypes de novo. We observed concordance with two of the TCGA subtypes; correlations for the mesenchymal-like and proliferative-like subtypes were 0.56-0.65. The mesenchymal-like subtype was more common in these AA women than in the TCGA EA women (33% versus 25%), and the proliferative-like subtype was marginally less common (14% versus 19%). Concordance for the differentiated-like subtype was considerably lower, at 0.21, and this subtype was less common in AA than EA women (19% versus 34%). Another subtype comprising 34% of the AA samples was only weakly correlated (-0.21-0.10) with any of the TCGA subtypes, suggesting that it is a novel subtype. The limited data available on HGSC in AA women suggest that at least two subtypes are comparable to those in EA women but differ in prevalence, and that there may be a novel subtype in AA women that does not strongly correspond to those described in EA women. Citation Format: Jennifer A. Doherty, Casey S. Greene, James E. Rudd, Laura J. Tafe, Anthony J. Alberg, Elisa V. Bandera, Jill Barnholtz-Sloan, Melissa Bondy, Michele L. Cote, Ellen Funkhouser, Patricia G. Moorman, Edward S. Peters, Ann G. Schwartz, Paul Terry, Rex Bentley, Andrew Berchuck, Jeffrey R. Marks, Joellen M. Schildkraut. Gene expression subtypes of high grade serous ovarian cancer in African American women. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 3407.

PCN173 - Carbohydrate intake and Breast Cancer risk in African American and European American Women in the Women’s circle of Health Study

Background: Although European American (EA) women have higher incidence of breast cancer than African American (AA) women, AA women are more often diagnosed with aggressive estrogen receptor negative (ER-) tumors, the risk of which increases with parity, lack of breastfeeding, and an early age at menarche. DNA methylation could be affected by reproductive factors and may be a potential molecular mechanism driving differences in tumor etiology. In a small study using fresh frozen breast tissue (n=58 AA, 80 EA), we previously found more differentially methylated loci (DMLs) in ER- tumors from AA and EA women than in ER+ tumors. Methods: To follow up on these preliminary findings, we used the Illumina 450K platform to determine genome-wide DNA methylation profiles in formalin fixed paraffin embedded (FFPE) breast tumors from 383 AA and 350 EA women who participated in the Women's Circle of Health Study, a case control study conducted in NY and NJ. We identified DMLs by race and ER status, as well as differentially methylated regions (DMRs). DMLs in eight genes were validated using the Sequenom EpiTYPER platform. Recursively partitioned mixture modeling (RPMM) package in R was used to examine relationships between methylation clusters and reproductive factors, information available from in-person interviews. In addition, using fresh frozen tumor tissue from 50 patients treated at Roswell Park Cancer Institute, we performed RNA sequencing on samples with methylation data available from a prior study, and used Spearmen's correlation to compare methylation and gene expression of DMLs and DMRs. Results: In assessing average methylation by location relative to CpG-islands (CGIs), we found that CGIs and shores in ER- tumors were significantly hypomethylated compared to CGI and shores in ER+ tumors from AA women, but not in tumors from EA women. We also identified 410 DMLs (Δβ>0.10 & FDR<0.05) between AA and EA breast tumors (race-associated DMLs, raDMLs), the majority of which were unique to ER- tumors (n = 260) and hypomethylated in AAs. These loci were enriched for immune response genes and several cell adhesion and inflammatory pathways. RPMM showed that parity, but not breastfeeding or age at menarche, was significantly associated with methylation class of ER- breast tumors. Of the genes that had ER- specific raDMLs, FOXA1 and THSD4 DNA methylation was highly correlated with gene expression (rho=-0.80, rho=+0.87, respectively; pvalue< 2.2x10-16). Summary: ER- tumors from AA women, but not from EA women, exhibited global hypomethylation at CGI and shores compared to ER+ tumors and contained the majority of raDMLs, many of which were associated with genes involved in immune and inflammatory response. The FOXA1 gene, which encodes a pioneer factor previously implicated in suppressing the molecular phenotype of basal breast cancer cells, was found to be methylated and silenced in the majority of ER- tumors analyzed for expression, consistent with aggressiveness of these tumors. These results, and the novel finding of associations between parity and DNA methylation signature, bring us a step forward in understanding the heterogeneous population of ER- tumors and provide insight into mechanisms of racial disparities in breast cancer. Citation Format: Allyson C. Espinal, Dan Wang, Lara Sucheston-Campbell, Song Liu, Qiang Hu, Li Tang, Gary Zirpoli, Thaer Khoury, Song Yao, Kitaw Demissie, Elisa V. Bandera, Christine B. Ambrosone, Michael J. Higgins. Methylation differences in breast tumor DNA from African American and European women are predominant in estrogen receptor (ER) negative breast cancer and are associated with childbearing. [abstract]. In: Proceedings of the Eighth AACR Conference on The Science of Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; Nov 13-16, 2015; Atlanta, GA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2016;25(3 Suppl):Abstract nr B47.

African American (AA) women are more likely than European American (EA) women to be diagnosed with early, aggressive breast cancer. Possible differences in innate immune pathways (e.g., inflammatory responses) have received little attention as potential mechanisms underlying this disparity. We evaluated distributions of selected genetic variants in innate immune pathways in AA and EA women, and examined their associations with breast cancer risk within the Women’s Circle of Health Study (WCHS). In stage I of the study (864 AA and 650 EA women) we found that genotype frequencies for 35 of 42 tested SNPs (18 candidate genes) differed between AAs and EAs (corroborated by ancestry informative markers). Among premenopausal AA women, comparing variant allele carriers to non-carriers, reduced breast cancer risk was associated with CXCL5-rs425535 (OR=0.61, P=0.02), while among EA women, there were associations with TNFA-rs1799724 (OR =2.31, P =0.002) and CRP-rs1205 (OR=0.54, P=0.01). For postmenopausal women, IL1B-rs1143627 (OR=1.80, P=0.02) and IL1B-rs16944 (OR=1.85, P =0.02) were associated with risk among EA women, with significant associations for TNFA-rs1799724 limited to estrogen receptor (ER) positive cancers (OR=2.0, P =0.001). However, none of the SNPs retained significance after Bonferroni adjustment for multiple testing at the level of P0.0012 (0.05/42) except for TNFA-rs1799724 in ER positive cancers. In a stage II validation (1,365 AA and 1,307 EA women), we extended evaluations for four SNPs (CCL2-rs4586, CRP-rs1205, CXCL5-rs425535, and IL1RN-rs4251961), which yielded similar results. In summary, distributions of variants in genes involved in innate immune pathways were found to differ between AA and EA populations, and showed differential associations with breast cancer according to menopausal or ER status. These results suggest that immune adaptations suited to ancestral environments may differentially influence breast cancer risk among EA and AA women.

Compared to European American (EA) women, African American (AA) women have higher rates of estrogen receptor negative (ER-) breast cancer, more specifically triple-negative (TN) subtype, and show poorer prognosis and survival. Increasing evidence suggests biological differences may contribute to the observed racial disparity. Studies evaluating racial differences in gene expression in breast tumor tissue have reported inconsistent results. Study of normal breast tissue in healthy women may provide new insight into biological mechanisms for cancer development prospectively before tumor occurrence. However, racial influence on gene expression in normal breast tissue has not been extensively studied. In this study, we evaluated racial differences in gene expression in normal breast tissue obtained from 23 healthy women as well as tumor tissue obtained from 108 breast cancer patients. We analyzed RNA-sequencing data and performed differential expression analysis between AA and EA women. We found that differentially expressed genes in normal breast tissue between AA and EA women were enriched in biological pathways related to amino acid metabolism, immune response and signaling, lipid and protein biosynthesis, and cell proliferation and survival. Many of these biological differences persist in tumor tissue between EA and AA women in a subtype-specific manner. For example, in ER- breast cancer, racial differences in gene expression were enriched in amino acid metabolism, cell proliferation and survival pathways, with particular enrichment in immune response and signaling and lipid metabolism pathways in TN breast cancer. For ER+ breast cancer, we did not find any major biological pathway enrichment. In addition, we identified several microRNAs differentially expressed in normal breast tissue between EA and AA women. They may be involved in racial differences in breast carcinogenesis but their potential downstream effects are yet to be determined. Future studies are needed to validate our findings and understand racial-specific biological mechanisms in breast cancer development. Citation Format: Aditi Shendre, Yunlong Liu, Anna Maria Storniolo, Bryan P. Schneider, Jiali Han, Chunyan He. Biological differences underlying racial disparity in breast cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr LB-163. doi:10.1158/1538-7445.AM2017-LB-163

Purpose of study: Female breast cancer is the second leading cause of cancer death in U.S. women, and the incidence of new breast cancer cases continues to increase. Despite slightly lower breast cancer incidence rates among African American (AA) compared to European American (EA) women in the U.S., AA women experience significantly higher breast cancer mortality. To better understand the extent to which environmental and genetic factors might help explain higher mortality rates among AA women, we examined the association between a measure of exposure to chemical pollutants and genomic profiling with breast cancer mortality among women with breast cancer in North Carolina. Procedures: Using a molecular epidemiologic approach, we examined the association of county hog concentration (a marker of environmental exposure to chemical pollutants) and genomic variations identified via targeted exome sequencing with age-adjusted breast cancer mortality rates among 146 women in North Carolina, stratified by race (AA vs. EA). The odds of breast cancer-specific mortality were estimated as a function of county hog concentration quintiles. Results: Overall, breast cancer mortality among AA women was higher than among EA women (OR=1.4, p<0.0001). Although there was no effect of hog concentration on breast cancer mortality of EA women, there was an increase in deaths from breast cancer in African American women in the highest quintile of hog concentration (OR=1.18, p=0.03), compared to the lower quintiles. In the lowest quintile of hog concentration, breast cancer mortality remained higher among AA versus EA women (OR=1.38, p=0.0002). This suggests that along with environmental factors, biological factors also contribute to disparities. Next, we performed targeted exome sequencing of breast cancer samples collected from a cohort in eastern North Carolina. AA breast cancer samples showed a high frequency of CNVs (copy number variations) of COL11A2, COL12A1, CYP21A2, LYRM2, COL9A1, DNAH11, and DST. EA breast cancer samples showed a high frequency of CNVs of PRG4, PLB1, CHRM5, OCA2, HMCN1, and MUC5B. Among these, HMCN1, MUC5B (among EA), and COL12A1, DNAH11, DST (among AA) were genes with significantly high CNVs identified from The Cancer Genome Atlas. Conclusions: Our findings suggest that living in a county with a high concentration of hogs may increase breast cancer mortality risk among AA women, and the high frequency of CNVs varies by race; both CNV and county hog concentration may contribute to racial disparities in breast cancer mortality among AA and EA women in North Carolina. Citation Format: Jung S. Byun, Sean Lee, Sijung Yun, Eliseo J. Perez-Stable, Anna M. Napoles, Paul Strickland, Kevin L. Gardner. Race, copy number variation, and local hog concentration in breast cancer mortality [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 1183.

Triple-negative breast cancer (TNBC) represents 10-20% of all invasive breast cancers and is characterized by a lack of expression of estrogen receptor, progesterone receptor, and human epidermal growth factor receptor 2. TNBC typically manifests as high-grade tumors often diagnosed at advanced stages, and affects younger patients, especially African American (AA) women. Dysregulation of miRNA expression levels contributes to TNBC pathogenesis and prognosis. Dysregulated miRNAs in advanced-stage cancers alter tumor progression, migration, and metastasis. Obesity is associated with miRNA dysregulation in adipose tissue, which is a driver of BC development and growth. This study aimed at identifying differentially expressed (DE) miRNA in TNBC patients of European American (EA) and AA women with obesity, compared to adjacent non-tumor tissues. miRNAseq data from 48 tissue samples (TNBC tumor and adjacent non-tumor) were analyzed for differential expression. Samples were from 12 EA and 12 AA patients, with 6 patients in each ethnic group having obesity and 6 normal weight, based on BMI estimates. Stringent comparisons, with and without obesity, were conducted to identify TNBC and obesity-associated miRNAs within each ethnic group. Prediction of miRNA-target genes was performed in miRWalk and Key Pathway Advisor (KPA) was employed for pathway enrichment analysis. Differential expression analysis between obese and normal-weight patients in each ethnic group revealed 79 DE miRNAs in EA and 40 in AA. We identified 55 miRNAs associated exclusively with tumors in obese patients within the EA group and 33 miRNAs within the AA group. Target gene analysis showed that in EA, 9 out of the 55 miRNAs interacted with 68 mRNAs, with miR-204-5p and miR-181b-5p accounting for 75% of interactions. In AA, 20 out of the 33 miRNAs interacted with 284 mRNAs with miR-20a-5p, -195-5p, -34a-5p, and -130a-3p with 65% of the interactions. KPA identified 84 and 330 pathways for EA and AA, respectively, with 43 common pathways,15 of them related to cancer processes sharing the gene targets GSKIP, TLBR1, TCF4, and TCF. Our study outlined unique miRNA profiles in TNBC among AA and EA women with obesity. Although common mRNAs were identified between ethnic groups, leading to the identification of common pathways on KPA, more than 50% of the identified pathways are related to unique biological processes associated with TNBC and obesity for each ethnic group. These findings underscore the importance of considering ethnic-specific miRNA signatures for understanding TNBC in the context of obesity, offering insights for targeted therapeutic strategies. Citation Format: Fokhrul Hossain, Martha Isabel González-Ramírez, Jone Garai, Xiao-Cheng Wu, Chindo Hicks, Luis Del Valle, Augusto Ochoa, Denise Danos, Lucio Miele, Jovanny Zabaleta. Identification of miRNA related to triple-negative breast cancer in African and European American women with obesity [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 5691.

Background: Within the U.S. population, African American (AA) women have a staggering 40% higher mortality rate from breast cancer than European American (EA) women, despite having a lower incidence rate. This disproportionate mortality burden imposed on AA women is rooted in both environmental and genetic causes. We are interested in elucidating molecular and environmental mechanisms that may be contributing to these breast cancer health disparities. Our recent study identified that higher neighborhood-level socioeconomic deprivation was associated with hypomethylation and decreased gene expression for LRIG1 (Leucine-rich repeats and immunoglobulin-like domains 1) in AA women, but not in EA women. LRIG1 has been shown to act as a tumor suppressor, associating with members of the ErbB family of receptor tyrosine kinases (RTKs), which includes the epidermal growth factor receptor (EGFR), HER2, HER3, and HER4. This association of LRIG1 with ErbBs is predicted to result in the degradation of these proteins and the suppression of pro-growth signaling. Objective: This project aims to determine differences in the protein expression of LRIG1 and ErbB proteins within breast epithelial cell lines (normal epithelial cells, estrogen receptor-positive (ER+), and estrogen receptor-negative (ER-)) derived from both AA and EA women. We hypothesize that there are differences in the protein expression of LRIG1 and ErbB proteins within breast epithelial cell lines derived from AA women and EA women. Methods: The levels of protein expression of LRIG1 and ErbB proteins in the cell lines were assessed using Western immunoblotting and densitometric analysis. The colocalization of LRIG1/EGFR and LRIG1/HER2 in non-tumorigenic, ER+, and ER- cell lines was assessed through immunofluorescence (IF) cell staining. Results: Western immunoblotting revealed substantial variation in target protein levels, with notable differences in LRIG1 protein levels by estrogen receptor status, with greater LRIG1 protein expression in ER+ cell lines. IF staining demonstrated limited colocalization between LRIG1 and EGFR as well as LRIG1 and HER2. Future experiments, including co-immunoprecipitation, will aim to determine how LRIG1 and the ErbB proteins are interacting and what factors may be influencing their binding and downstream signaling. Conclusions: Our results provide insight into LRIG1 and ErbB co-expression in several breast cell lines from AA and EA women. Our next steps will include identifying distinct differences between these cell lines that might be a result of variations in environmental factors, the tumor microenvironment, and genetic ancestry. Citation Format: Amber Yu, Angel H. Pajimola, Kayla S. Ingram, Brittany Jenkins-Lord. Investigating the tumor suppressive role of LRIG1 in breast cancer disparities [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 1 (Regular Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_1):Abstract nr 6726.

Racial disparity in breast cancer is well recognized. Compared to European American (EA) women, African American (AA) women are more often diagnosed with breast cancer at younger ages, have a more advanced or aggressive disease, and have poorer outcomes. Increasing evidence suggests that biological differences between EA and AA women, particularly differences in epigenetic changes of DNA methylation (DNAm), may contribute to the observed cancer disparity. We hypothesize that racial differences in DNAm in normal breast tissue may reflect distinct genomic susceptibility to breast cancer in different racial groups. Therefore, we investigated epigenome-wide differences of DNAm in normal breast tissue between 178 EA and 272 AA women using the Illumina TruSeq Methyl Capture EPIC library and NGS technology. We identified 17,340 differentially methylated CpG loci (DMLs) between EA and AA women, of which 7,744 were hypermethylated in AA women and 9,596 were hypermethylated in EA women. Pathway analyses of genes annotated to these racial DMLs suggested enrichment of biological processes including cell movement, cell motility, and cell migration, features that are likely linked to the aggressiveness and metastatic potentials of tumor cells. We further examined racial differences in DNAm of breast cancer-related candidate genes and GWAS-identified breast cancer risk loci. Approximately 30% of candidate genes were found to have racial differences in DNAm at more than three CpG sites and these candidate genes were enriched for pathways related to response to stimulus and anatomic structure development. Most interestingly, racial DMLs were found to be enriched for breast cancer risk loci that are associated with risk of estrogen-receptor negative (ER-) breast cancer, treatment response to aromatase inhibitor, and breast cancer-specific morality, phenotypes of which we observed differences between EA and AA breast cancer patients. Our results suggest that racial differences in DNAm in normal breast tissue may induce different biological processes that lead to distinct clinical features of breast tumors observed in EA and AA women and provide an epigenetic mechanism underlying the observed racial disparities. Further research is need to validate the findings of this study. Citation Format: Nan Lin, James Castle, Jinpeng Liu, Chunyan He. Racial differences of epigenome in normal breast tissue reveal biological pathways implicated in racial disparities in breast cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 1937.

Given that suicide is the second leading cause of death among college students, it is important to identify risk factors that may contribute to college students’ suicide. Our study examined the differences in risk factors of suicidal ideation between 99 African American and 529 European American college women (18–24 years old). The only significant difference that was reported between the two groups of women was on hopelessness, with African American women having lower hopelessness scores. In hierarchical regression analyses, reports of hopelessness, depression, and perceived burdensomeness, but not thwarted belongingness, significantly predicted suicidal ideation in college women. Furthermore, race moderated the relationship between hopelessness and suicidal ideation such that hopelessness was a stronger predictor for African American women than it was for European American women. Race also moderated the depression–suicidal ideation association, with depression emerging as a stronger predictor of suicidal ideation for European American than for African American women. When assessing risk for suicide, our results suggest that practitioners may need to focus more on hopelessness in African American women and more on depression in European American women while also considering perceived burdensomeness in college women regardless of race. In addition to assessment, prevention programs which target these identified risk factors for suicidality should be developed specifically for African American and European American college women.

Introduction: Over the last several decades, the concern of environmental exposures to certain carcinogens and mutagens found in hair products, particularly hair dyes, have been explored for evidence of an association with breast cancer risk, yielding equivocal results. However, little is known about this association among African American (AA) women, who are common users of these products. The objective of this study was to examine the prevalence and patterns of use of hair products in AA and European American (EA) women in the Women's Circle of Health Study (WCHS), and their associations with breast cancer risk, overall and by estrogen receptor (ER+, ER-) and triple negative (TN) status. Methods: Data collection for the WCHS, a case-control study of breast cancer in New York City and several counties in New Jersey, was conducted through in-person interviews, with anthropometric and body composition measurements taken, and review of pathology records. At study entry, participants were asked on use of hair dyes, chemical relaxers/straighteners and cholesterol- and/or placenta-containing conditioning creams. Chi-square tests were used to compare differences in hair product variables by case-control status among AAs and EAs. Race-stratified, age-adjusted and multivariable-adjusted unconditional logistic regression models controlling for age, race, education, family history of breast cancer, oral contraceptive use, and body mass index were used to estimate odds ratios (OR) and 95% confidence intervals (CI) for associations between hair product use and risk among 4,285 women with breast cancer and controls (AA, n=2,798 and EA, n=1,487). Results: Among controls, 30.23% of AAs and 57.76% of EAs regularly used hair dye. Compared to light hair dye shades (blonde, light brown) use of darker shades (dark brown, black) was associated with increased odds of breast cancer among AA women (OR 1.64, 95% CI: 1.19-2.27), although there did not appear to be a dose response association with frequency of use. There were no associations between hair dye use and breast cancer risk among EA women. Use of chemical relaxers was more common among AAs than EAs (87.13% vs. 4.62% of AA and EA controls, respectively). Compared to AA women who used chemical relaxers without lye, those using products with lye were at increased risk (OR 1.54, 95% CI: 1.22-1.94). Among EA women although use of relaxers was not very common, compared to never users, those using relaxers (OR 1.74, 95% CI: 1.11-2.74) and using lye-containing relaxers (OR 4.37, 95% CI: 1.65-11.88) were at increased risk. Regular hair dye use (OR 1.20, 95% CI: 1.03-1.39), use of darker hair dye shades (OR 1.37, 95% CI: 1.05-1.77), and use of relaxers that contain lye (OR 1.26, 95% CI: 1.03-1.55) were associated with increased risk of ER+ BC. Regularly using both hair dyes and relaxers was associated with increased risk of ER+ BC (OR 1.20, 95% CI: 1.00-1.44). Regular hair dye use was not associated with risk of ER- or TNBC. The use of deep conditioning creams that contain cholesterol or placenta was also more common among AAs than EAs (56.12% vs. 6.01% of controls, respectively). However, there were no associations between use of these products and breast cancer risk. Conclusions: These findings from a large case-control study of AA and EA women provide additional epidemiological data to support a relationship between the use of some hair products, namely hair dyes and chemical relaxers, and risk of breast cancer. As use of various hair products and other cosmetics continue to increase among women in the U.S., particularly those at increased risk of breast cancer, improved awareness of the potential effects of exposures to their chemical ingredients are needed. Citation Format: Adana A.M. Llanos, Anna Rabkin, Gary Zirpoli, Cathleen Y. Xing, Bo Qin, Brian D. Gonzalez, Chi-Chen Hong, Kitaw Demissie, Elisa V. Bandera, Christine B. Ambrosone. Hair product use and breast cancer risk by hormone receptor status in the Women's Circle of Health Study. [abstract]. In: Proceedings of the Ninth AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2016 Sep 25-28; Fort Lauderdale, FL. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2017;26(2 Suppl):Abstract nr B81.

Limiting energy-dense foods, fast foods, and sugary drinks that promote weight gain is a cancer prevention recommendation, but no studies have evaluated intake in relation to breast cancer risk in African American (AA) women. In a case-control study with 1692 AA women (803 cases and 889 controls) and 1456 European American (EA) women (755 cases and 701 controls), odds ratios (OR) and 95% confidence intervals (CI) for risk were computed, stratifying for menopausal and estrogen receptor (ER) status. Among postmenopausal EA women, breast cancer risk was associated with frequent consumption of energy-dense foods (OR = 2.95; 95% CI: 1.66–5.22), fast foods (OR = 2.35; 95% CI: 1.38–4.00), and sugary drinks (OR = 2.05; 95% CI: 1.13–3.70). Elevated risk of ER+ tumors in EA women was associated with energy-dense (OR = 1.75; 95% CI: 1.14–2.69) and fast foods (OR = 1.84; 95% CI: 1.22–2.77). Among AA women, frequent fast food consumption was related to premenopausal breast cancer risk (OR = 1.97; 95% CI: 1.13–3.43), and with ER+ tumors. Energy adjustment attenuated risk estimates in AA women, while strengthening them among EA women. Frequent consumption of energy-dense and fast foods that have poor nutritive value appeared to increase breast cancer risk in AA and EA women, with differences by menopausal status and ER status.

BackgroundCervical cancer, a rare outcome of high-risk human papillomavirus (HPV) infection, disproportionately affects African American women, who are about twice more likely than European American women to die of the disease. Most cervical HPV infections clear in about one year. However, in some women HPV persists, posing a greater risk for cervical dysplasia and cancer. The Carolina Women’s Care Study (CWCS) was conducted to explore the biological, genetic, and lifestyle determinants of persistent HPV infection in college-aged European American and African American women. This paper presents the initial results of the CWCS, based upon data obtained at enrollment.MethodsFreshman female students attending the University of South Carolina were enrolled in the CWCS and followed until graduation with biannual visits, including two Papanicolaou tests, cervical mucus collection, and a questionnaire assessing lifestyle factors. We recruited 467 women, 293 of whom completed four or more visits for a total of 2274 visits.Results and conclusionCWCS participants were 70% European American, 24% African American, 3% Latina/Hispanic, and 3% Asian. At enrollment, 32% tested positive for any HPV. HPV16 infection was the most common (18% of infections). Together, HPV16, 66, 51, 52, and 18 accounted for 58% of all HPV infections. Sixty-four percent of all HPV-positive samples contained more than one HPV type, with an average of 2.2 HPV types per HPV-positive participant. We found differences between African American and European American women in the prevalence of HPV infection (38.1% African American, 30.7% European American) and abnormal Papanicolaou test results (9.8% African-American, 5.8% European American). While these differences did not reach statistical significance at enrollment, as the longitudinal data of this cohort are analyzed, the sample size will allow us to confirm these results and compare the natural history of HPV infection in college-aged African American and European American women.