Differential expression of breast cancer-associated genes between stage- and age-matched tumor specimens from African- and Caucasian-American Women diagnosed with breast cancer

Grunda, Jessica M.; Steg, Adam D.; He, Q. Peter; Steciuk, Mark; Byan-Parker, Suzanne; Johnson, Martin R.; Grizzle, William E.

doi:10.1186/1756-0500-5-248

Cited by 37 publications

(29 citation statements)

References 95 publications

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“…This comparison was our only comparison where ESR1 was differentially expressed between AA and CA samples, and Grunda et al saw a similar decrease in expression of ESR1 in their study [21]. We believe this finding suggests that AA women may have reduced ER expression in later stages or that AA women may be more susceptible to mutations causing the ER- phenotype.…”

Section: Discussionsupporting

confidence: 69%

Differentially Expressed Transcripts and Dysregulated Signaling Pathways and Networks in African American Breast Cancer

et al. 2013

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African Americans (AAs) have higher mortality rate from breast cancer than that of Caucasian Americans (CAs) even when socioeconomic factors are accounted for. To better understand the driving biological factors of this health disparity, we performed a comprehensive differential gene expression analysis, including subtype- and stage-specific analysis, using the breast cancer data in the Cancer Genome Atlas (TCGA). In total, 674 unique genes and other transcripts were found differentially expressed between these two populations. The numbers of differentially expressed genes between AA and CA patients increased in each stage of tumor progression: there were 26 in stage I, 161 in stage II, and 223 in stage III. Resistin, a gene that is linked to obesity, insulin resistance, and breast cancer, was expressed more than four times higher in AA tumors. An uncharacterized, long, non-coding RNA, LOC90784, was down-regulated in AA tumors, and its expression was inversely related to cancer stage and was the lowest in triple negative AA breast tumors. Network analysis showed increased expression of a majority of components in p53 and BRCA1 subnetworks in AA breast tumor samples, and members of the aurora B and polo-like kinase signaling pathways were also highly expressed. Higher gene expression diversity was observed in more advanced stage breast tumors suggesting increased genomic instability during tumor progression. Amplified resistin expression may indicate insulin-resistant type II diabetes and obesity are associated with AA breast cancer. Expression of LOC90784 may have a protective effect on breast cancer patients, and its loss, particularly in triple negative breast cancer, could be having detrimental effects. This work helps elucidate molecular mechanisms of breast cancer health disparity and identifies putative biomarkers and therapeutic targets such as resistin, and the aurora B and polo-like kinase signaling pathways for treating AA breast cancer patients.

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Section: Discussionsupporting

confidence: 69%

Differentially Expressed Transcripts and Dysregulated Signaling Pathways and Networks in African American Breast Cancer

et al. 2013

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“…While aggressive forms of BC disproportionately affect AA women, this does not fully explain the disparities; even within subtype there are differences in survival by race. From previous studies we have learned that: 1) survival differences exist between AA and CAU despite equal treatment [5] or tumor subtype [3] and 2) genes are differentially expressed between AA and CAU tumors even when matching on clinical features [6, 7, 9]. Genes that are both differentially expressed by race in tumors, and confer a survival disadvantage could explain a portion of the observed racial survival disparity, although to date no study had evaluated whether race-associated genes conferred a survival disadvantage.…”

Section: Discussionmentioning

confidence: 99%

“…They reported that independent of ER status, 19 and eight genes were differentially expressed in the breast tumor stroma and epithelium, respectively, of 18 AA and 17 CAU women. Grunda et al [7] evaluated expression of 84 genes associated with breast cancer aggressiveness, prognosis and response to therapy, and found that 20 of these genes were differentially expressed in 12 AA and 12 CAU age- and stage-matched breast tumors. Field et al [6] identified genes that were differentially expressed in 26 AA and 26 CAU age, grade and ER-matched breast tumors.…”

Section: Introductionmentioning

confidence: 99%

Race-associated biological differences among Luminal A breast tumors

D’Arcy

Fleming

Robinson

et al. 2015

Breast Cancer Res Treat

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Purpose African American (AA) women have higher breast-cancer specific mortality rates. A higher prevalence of the worse outcome Basal-like breast cancer subtype contributes to this, but AA women also have higher mortality even within the more favorable outcomes Luminal A breast cancers. These differences may reflect treatment or health care access issues, inherent biological differences, or both. Methods To identify potential biological differences by race among Luminal A breast cancers, gene expression data from 108 CAU and 57 AA breast tumors were analyzed. Race-associated genes were next evaluated for associations with survival. Finally, expression of race- and survival-associated genes was evaluated in normal tissue of AA and CAU women. Results Six genes (ACOX2, MUC1, CRYBB2, PSPH, SQLE, TYMS) were differentially expressed by race among Luminal A breast cancers and were associated with survival (HR < 0.8, HR > 1.25). For all six genes, tumors in AA had higher expression of poor prognosis genes (CRYBB2, PSPH, SQLE, TYMS) and lower expression of good prognosis genes (ACOX2, MUC1). A score based on all six genes predicted survival in a large independent dataset (HR = 1.9 top vs. bottom quartile, 95% CI: 1.4 – 2.5). For four genes, normal tissue of AA and CAU women showed similar expression (ACOX2, MUC1, SQLE, TYMS), however, the poor outcome associated genes CRYBB2 and PSPH were more highly expressed in AA vs. CAU women’s normal tissue. Conclusions This analysis identified gene expression differences that may contribute to mortality disparities and suggests that among Luminal A breast tumors there are biological differences between AA and CAU patients. Some of these differences (CRYBB2 and PSPH) may exist from the earliest stages of tumor development, or even precede malignancy.

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“…Black women with HR positive breast cancer have a much higher mortality rate in the first two years after diagnosis than whites,[34] but among those with TNBC, there is conflicting data on survival outcomes according to race. [16, 19, 21, 26, 28, 29, 33, 34] Although studies in breast cancer patients in general have identified racial differences in genomic profiles,[10, 13] it is unclear if these differences are being driven by those with HR positive cancers or TNBC. To address this lack of data, we sought to investigate racial differences in the genetic landscape of TNBC.…”

Section: Introductionmentioning

confidence: 99%

Differences in the mutational landscape of triple-negative breast cancer in African Americans and Caucasians

Ademuyiwa

Tao

Luo

et al. 2016

Breast Cancer Res Treat

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Background Triple negative breast cancer (TNBC) occurs at higher frequency in African Americans compared with Caucasians. It is unclear if the biology of TNBC is different in African American versus Caucasians. In this study, we sought to evaluate racial differences in the molecular pathology of TNBC. Methods Using data from The Cancer Genome Atlas, we identified TNBC patients with information on race. We analyzed differences in clinical characteristics, tumor somatic mutations, and gene expression patterns by race from whole exome and microarray data. Results 1104 patients were identified, of which 178 had TNBC. TNBC was more frequent in African American than Caucasians (33.3% vs 14.9%). Although, more African American than Caucasians overall were classified as basal-like from PAM50 gene expression (34.8% vs 16.1%), no differences in the TNBC cohort were observed. Median tumor somatic mutation counts were higher in African American versus Caucasians (39.5 vs 34), but no racial differences in the mutation counts in TNBC were observed. Somatic mutation analysis revealed racial differences in specific high prevalence genes in all patients- [TP53: 46% in African American vs 27% in Caucasians; PIK3CA: 23% in African American vs 34% in Caucasians; and MLL3: 12% in African American vs 6% in Caucasians]. TNBC patients did not have any specific high prevalence genes associated with racial differences. There were no racial differences in gene expression patterns in selected genes involved in breast cancer biology. Overall, African Americans had shorter TTP and worse DFS. Racial differences in clinical outcomes were not observed in TNBC. Conclusion The mutational landscape of TNBC is similar between African Americans and Caucasians. The higher frequency of TNBC in African Americans is therefore not associated with a different genomic profile of common established tumor regulatory pathway genes. Other modifiable factors may exist that contribute to the racial disparity in TNBC.

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Differential expression of breast cancer-associated genes between stage- and age-matched tumor specimens from African- and Caucasian-American Women diagnosed with breast cancer

Cited by 37 publications

References 95 publications

Differentially Expressed Transcripts and Dysregulated Signaling Pathways and Networks in African American Breast Cancer

Differentially Expressed Transcripts and Dysregulated Signaling Pathways and Networks in African American Breast Cancer

Race-associated biological differences among Luminal A breast tumors

Differences in the mutational landscape of triple-negative breast cancer in African Americans and Caucasians

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