The POZ-ZF transcription factor Kaiso was discovered two decades ago as a binding partner for p120ctn. Since its discovery, roles for Kaiso in diverse biological processes (epithelial-to-mesenchymal transition, apoptosis, inflammation) and several signalling pathways (Wnt/β-catenin, TGFβ, EGFR, Notch) have emerged. While Kaiso’s biological role in normal tissues has yet to be fully elucidated, Kaiso has been increasingly implicated in multiple human cancers including colon, prostate, ovarian lung, breast and chronic myeloid leukemia. In the majority of human cancers investigated to date, high Kaiso expression correlates with aggressive tumor characteristics including proliferation and metastasis, and/or poor prognosis. More recently, interest in Kaiso stems from its apparent correlation with racial disparities in breast and prostate cancer incidence and survival outcomes in people of African Ancestry. This review discusses Kaiso’s role in various cancers, and Kaiso’s potential for driving racial disparities in incidence and/or outcomes in people of African ancestry.

BackgroundDepressive disorder is the largest contributor to years lived with disability in the Caribbean, adding 948 per 100,000 in 2013. Depression is also a major risk factor for suicidal behaviour. Social inequalities influence the occurrence of depression, yet little is known about the social inequalities of this condition in the Caribbean. In support of the 2011 Rio Political Declaration on addressing health inequities, this article presents a systematic review of the role of social determinants on depression and its suicidal behaviours in the Caribbean.MethodsEight databases were searched for observational studies reporting associations between social determinants and depression frequency, severity, or outcomes. Based on the PROGRESS-plus checklist, we considered 9 social determinant groups (of 15 endpoints) for 6 depression endpoints, totalling 90 possible ways (‘relationship groups’) to explore the role of social determinants on depression. Studies with ≥50 participants conducted in Caribbean territories between 2004 and 2014 were eligible. The review was conducted according to STROBE and PRISMA guidelines. Results were planned as a narrative synthesis, with meta-analysis if possible.ResultsFrom 3951 citations, 55 articles from 45 studies were included. Most were classified as serious risk of bias. Fifty-seven relationship groups were reported by the 55 included articles, leaving 33 relationship groups (37%) without an evidence base. Most associations were reported for gender, age, residence, marital status, and education. Depression, its severity, and its outcomes were more common among females (except suicide which was more common among males), early and middle adolescents (among youth), and those with lower levels of education. Marriage emerged as both a risk and protective factor for depression score and prevalence, while several inequality relationships in Haiti were in contrast to typical trends.ConclusionThe risk of bias and few numbers of studies within relationship groups restricted the synthesis of Caribbean evidence on social inequalities of depression. Along with more research focusing on regional social inequalities, attempts at standardizing reporting guidelines for observational studies of inequality and studies examining depression is necessitated. This review offers as a benchmark to prioritize future research into the social determinants of depression frequency and outcomes in the Caribbean.Electronic supplementary materialThe online version of this article (doi:10.1186/s12889-017-4371-z) contains supplementary material, which is available to authorized users.

Triple negative breast cancers (TNBC) are highly aggressive and lack specific targeted therapies. Recent studies have reported high expression of the transcription factor Kaiso in triple negative tumors, and this correlates with their increased aggressiveness. However, little is known about the clinical relevance of Kaiso in the growth and survival of TNBCs. Herein, we report that Kaiso depletion attenuates TNBC cell proliferation, and delays tumor onset in mice xenografted with the aggressive MDA-231 breast tumor cells. We further demonstrate that Kaiso depletion attenuates the survival of TNBC cells and increases their propensity for apoptotic-mediated cell death. Notably, Kaiso depletion downregulates BRCA1 expression in TNBC cells expressing mutant-p53 and we found that high Kaiso and BRCA1 expression correlates with a poor overall survival in breast cancer patients. Collectively, our findings reveal a role for Kaiso in the proliferation and survival of TNBC cells, and suggest a relevant role for Kaiso in the prognosis and treatment of TNBCs.

PurposeTriple-negative breast cancer (TNBC) is most prevalent in young women of African ancestry (WAA) compared to women of other ethnicities. Recent studies found a correlation between high expression of the transcription factor Kaiso, TNBC aggressiveness, and ethnicity. However, little is known about Kaiso expression and localization patterns in TNBC tissues of WAA. Herein, we analyze Kaiso expression patterns in TNBC tissues of African (Nigerian), Caribbean (Barbados), African American (AA), and Caucasian American (CA) women.MethodsFormalin-fixed and paraffin embedded (FFPE) TNBC tissue blocks from Nigeria and Barbados were utilized to construct a Nigerian/Barbadian tissue microarray (NB-TMA). This NB-TMA and a commercially available TMA comprising AA and CA TNBC tissues (AA-CA-YTMA) were subjected to immunohistochemistry to assess Kaiso expression and subcellular localization patterns, and correlate Kaiso expression with TNBC clinical features.ResultsNigerian and Barbadian women in our study were diagnosed with TNBC at a younger age than AA and CA women. Nuclear and cytoplasmic Kaiso expression was observed in all tissues analyzed. Analysis of Kaiso expression in the NB-TMA and AA-CA-YTMA revealed that nuclear Kaiso H scores were significantly higher in Nigerian, Barbadian, and AA women compared with CA women. However, there was no statistically significant difference in nuclear Kaiso expression between Nigerian versus Barbadian women, or Barbadian versus AA women.ConclusionsHigh levels of nuclear Kaiso expression were detected in patients with a higher degree of African heritage compared to their Caucasian counterparts, suggesting a role for Kaiso in TNBC racial disparity.Electronic supplementary materialThe online version of this article (doi:10.1007/s10552-017-0955-2) contains supplementary material, which is available to authorized users.

BackgroundBreast cancer is the leading cause of cancer deaths among women in the Caribbean and accounts for >1 million disability adjusted life years. Little is known about the social inequalities of this disease in the Caribbean. In support of the Rio Political Declaration on addressing health inequities, this article presents a systematic review of evidence on the distribution, by social determinants, of breast cancer risk factors, frequency, and adverse outcomes in Caribbean women.MethodsMEDLINE, EMBASE, SciELO, CINAHL, CUMED, LILACS, and IBECS were searched for observational studies reporting associations between social determinants and breast cancer risk factors, frequency, or outcomes. Based on the PROGRESS-plus checklist, we considered 8 social determinant groups for 14 breast cancer endpoints, which totalled to 189 possible ways (‘relationship groups’) to explore the role of social determinants on breast cancer. Studies with >50 participants conducted in Caribbean territories between 2004 and 2014 were eligible for inclusion. The review was conducted according to STROBE and PRISMA guidelines and results were planned as a narrative synthesis, with meta-analysis if possible.ResultsThirty-four articles were included from 5,190 screened citations. From these included studies, 75 inequality relationships were reported examining 30 distinct relationship groups, leaving 84% of relationship groups unexplored. Most inequality relationships were reported for risk factors, particularly alcohol and overweight/obesity which generally showed a positive relationship with indicators of lower socioeconomic position. Evidence for breast cancer frequency and outcomes was scarce. Unmarried women tended to have a higher likelihood of being diagnosed with breast cancer when compared to married women. While no association was observed between breast cancer frequency and ethnicity, mortality from breast cancer was shown to be slightly higher among Asian-Indian compared to African-descent populations in Trinidad (OR 1.2, 95% CI 1.1–1.4) and Guyana (OR 1.3, 95% CI 1.0–1.6).ConclusionStudy quantity, quality, and variability in outcomes and reporting limited the synthesis of evidence on the role of social determinants on breast cancer in the Caribbean. This report represents important current evidence on the region, and can guide future research priorities for better describing and understanding of Caribbean breast cancer inequalities.Electronic supplementary materialThe online version of this article (doi:10.1186/s12939-017-0540-z) contains supplementary material, which is available to authorized users.