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1.
Cancer Med ; 13(5): e7100, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38491836

RESUMO

INTRODUCTION: California is home to the largest population of Armenians in the United States. The historical categorization of Armenians as 'White' or 'Some Other Race' in population databases has likely masked cancer incidence patterns in this population. This is the first study considering cancer incidence among Armenians in California. METHODS: We used the Armenian Surname List and birthplace information in the California Cancer Registry to identify Armenians with cancer diagnosed during 1988-2019. We calculated proportional incidence ratios (PIR) among Armenians compared with non-Hispanic Whites (NHWs). As an exploratory analysis, we calculated incidence rate ratios (IRR) during 2006-2015 using Armenian population denominators from the American Community Survey (ACS). We selected PIR as our primary method given uncertainty regarding the use of ACS population estimates for rate calculations. RESULTS: There were 27,212 cancer diagnoses among Armenians in California, 13,754 among males and 13,458 among females. Armenian males had notably higher proportions of stomach (PIR = 2.39), thyroid (PIR = 1.45), and tobacco-related cancers including bladder (PIR = 1.53), colorectal (PIR = 1.29), and lung (PIR = 1.16) cancers. Higher proportional incidence of cancers including stomach (PIR = 3.24), thyroid (PIR = 1.47), and colorectal (PIR = 1.29) were observed among Armenian females. Exploratory IRR analyses showed higher stomach (IRR = 1.78), bladder (IRR = 1.13), and colorectal (IRR = 1.12) cancers among Armenian males and higher stomach (IRR = 2.54) cancer among Armenian females. CONCLUSION: We observed higher stomach, colorectal and thyroid cancer incidence among males and females, and tobacco-related cancers among males. Further research is needed to refine Armenian population estimates and understand and address risk factors associated with specific cancers among Armenians in California.


Assuntos
Neoplasias Colorretais , População do Leste Europeu , Neoplasias da Glândula Tireoide , Masculino , Feminino , Humanos , Estados Unidos , Incidência , California/epidemiologia
2.
BMC Public Health ; 24(1): 123, 2024 01 09.
Artigo em Inglês | MEDLINE | ID: mdl-38195461

RESUMO

BACKGROUND: Community-acquired Staphylococcus aureus (CA-Sa) skin and soft tissue infections (SSTIs) are historically associated with densely populated urban areas experiencing high poverty rates, intravenous drug use, and homelessness. However, the epidemiology of CA-Sa SSTIs in the United States has been poorly understood since the plateau of the Community-acquired Methicillin-resistant Staphylococcus aureus epidemic in 2010. This study examines the spatial variation of CA-Sa SSTIs in a large, geographically heterogeneous population and identifies neighborhood characteristics associated with increased infection risk. METHODS: Using a unique neighborhood boundary, California Medical Service Study Areas, a hotspot analysis, and estimates of neighborhood infection risk ratios were conducted for all CA-Sa SSTIs presented in non-Federal California emergency departments between 2016 and 2019. A Bayesian Poisson regression model evaluated the association between neighborhood-level infection risk and population structure, neighborhood poverty rates, and being a healthcare shortage area. RESULTS: Emergency departments in more rural and mountainous parts of California experienced a higher burden of CA-Sa SSTIs between 2016 and 2019. Neighborhoods with high infection rates were more likely to have a high percentage of adults living below the federal poverty level and be a designated healthcare shortage area. Measures of population structure were not associated with infection risk in California neighborhoods. CONCLUSIONS: Our results highlight a potential change in the epidemiology of CA-Sa SSTIs in California emergency departments. Future studies should investigate the CA-Sa burden in other geographies to identify whether this shift in epidemiology holds across other states and populations. Further, a more thorough evaluation of potential mechanisms for the clustering of infections seen across California neighborhoods is needed.


Assuntos
Staphylococcus aureus Resistente à Meticilina , Infecções dos Tecidos Moles , Infecções Estafilocócicas , Adulto , Humanos , Staphylococcus aureus , Infecções dos Tecidos Moles/epidemiologia , Teorema de Bayes , Infecções Estafilocócicas/epidemiologia , California/epidemiologia , Serviço Hospitalar de Emergência
3.
Nat Hum Behav ; 8(1): 6-7, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-38052963

Assuntos
Menopausa , Feminino , Humanos
4.
Sci Rep ; 13(1): 21324, 2023 12 03.
Artigo em Inglês | MEDLINE | ID: mdl-38044375

RESUMO

Triple negative breast cancer (TNBC) is highly immunogenic and high levels of tumor infiltrating lymphocytes (TILs) have been associated with a better prognosis and higher probability to achieve pathological complete response. Here, we explore the potential role of stromal TILs level and composition as a prognostic and predictive biomarker in TNBC. 195 Tumor biospecimens from patients diagnosed with TNBC were included. Stromal TILs (sTILs), positive CD4/CD8 cells were evaluated. Differences in clinic-pathological characteristics according to immune infiltration were assessed. The predictive and prognostic value of immune infiltration was analyzed by multivariate models. Higher immune infiltration was observed in patients with favorable clinical-pathological features. Survival analysis showed that longer overall survival times were observed in patients with a higher infiltration of sTILs (p = 0.00043), CD4 + (p = 0.0074) and CD8 + (p = 0.008). In the multivariate analysis, low levels of sTILs were found to be associated with a higher mortality hazard (HR: 1.59, 95% CI 1.01-2.48). CD4 and CD8 immune infiltration were associated with higher odds for pathological complete response (OR: 1.20, 95% CI 1.00-1.46, OR: 1.28, 1.02-1.65, respectively). Our results suggest that immune infiltration could be used as a prognostic marker for overall survival in TNBC patients.


Assuntos
Neoplasias de Mama Triplo Negativas , Humanos , Neoplasias de Mama Triplo Negativas/patologia , Linfócitos do Interstício Tumoral , Colômbia , Prognóstico , Biomarcadores , Biomarcadores Tumorais/análise
5.
J Genet Couns ; 32(6): 1226-1231, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-37747056

RESUMO

Breast cancer is the most common cancer in women in the United States (U.S.) and the leading cause of cancer related death among U.S. Hispanics/Latinas (H/Ls). H/Ls have lower rates of screening and longer time to follow up after an abnormal mammogram. We developed a comprehensive community health educator (promotores)-led education and risk identification program for Spanish-speaking H/Ls in California to increase mammography screening, genetic testing, and the understanding of the impact of family history on cancer risk. Due to COVID-19, we adapted the program to a virtual platform. The experience of transforming the program to a virtual platform provided unique opportunities for collaboration between researchers, community partners, and participants. Promotores are major partners in community based participatory research and in the provision of health care services, but their voices are often excluded from scientific reports. This commentary is an effort to provide a platform for promotores to share their experiences and for the readers to understand their approach in bridging the gap between health care services and communities.


Assuntos
Neoplasias da Mama , Humanos , Feminino , Estados Unidos , Neoplasias da Mama/diagnóstico , Neoplasias da Mama/genética , Mamografia , Saúde Pública , Hispânico ou Latino
6.
Health Place ; 83: 103094, 2023 09.
Artigo em Inglês | MEDLINE | ID: mdl-37515963

RESUMO

Poverty is an often-cited driver of health disparities, and associations between poverty and community-acquired Methicillin-resistant Staphylococcus aureus (CA-MRSA) infection are well documented. However, the pathways through which poverty influences infection have not been thoroughly examined. This project aims to identify mediating variables, or mechanisms, explaining why area-level poverty is associated with CA-MRSA infection in Californians. Bayesian multilevel models accounting for spatial confounding were developed to test whether the association between area-level poverty and CA-MRSA infection is mediated by living in a primary care shortage area (HCSA), living near an adult correctional facility, and residential environmental degradation. The association between area-level poverty and CA-MRSA infection can be partially explained by spatial autocorrelation, living in an HCSA, and environmental degradation in the neighborhood. Combined, the mediators explain approximately 6% of the odds of CA-MRSA infection for individuals living in neighborhoods with high poverty rates and 50% of the statistical association between area-level poverty and CA-MRSA infection. The statistical association between area-level poverty and infection was completely explained by the mediators for individuals living in neighborhoods with low poverty rates.


Assuntos
Infecções Comunitárias Adquiridas , Staphylococcus aureus Resistente à Meticilina , Infecções Estafilocócicas , Adulto , Humanos , Teorema de Bayes , Análise Multinível , Infecções Estafilocócicas/epidemiologia , Infecções Comunitárias Adquiridas/epidemiologia , Pobreza , California/epidemiologia
7.
Cancer Res ; 83(15): 2600-2613, 2023 08 01.
Artigo em Inglês | MEDLINE | ID: mdl-37145128

RESUMO

Somatic mutational profiling is increasingly being used to identify potential targets for breast cancer. However, limited tumor-sequencing data from Hispanic/Latinas (H/L) are available to guide treatment. To address this gap, we performed whole-exome sequencing (WES) and RNA sequencing on 146 tumors and WES of matched germline DNA from 140 H/L women in California. Tumor intrinsic subtype, somatic mutations, copy-number alterations, and expression profiles of the tumors were characterized and compared with data from tumors of non-Hispanic White (White) women in The Cancer Genome Atlas (TCGA). Eight genes were significantly mutated in the H/L tumors including PIK3CA, TP53, GATA3, MAP3K1, CDH1, CBFB, PTEN, and RUNX1; the prevalence of mutations in these genes was similar to that observed in White women in TCGA. Four previously reported Catalogue of Somatic Mutations in Cancer (COSMIC) mutation signatures (1, 2, 3, 13) were found in the H/L dataset, along with signature 16 that has not been previously reported in other breast cancer datasets. Recurrent amplifications were observed in breast cancer drivers including MYC, FGFR1, CCND1, and ERBB2, as well as a recurrent amplification in 17q11.2 associated with high KIAA0100 gene expression that has been implicated in breast cancer aggressiveness. In conclusion, this study identified a higher prevalence of COSMIC signature 16 and a recurrent copy-number amplification affecting expression of KIAA0100 in breast tumors from H/L compared with White women. These results highlight the necessity of studying underrepresented populations. SIGNIFICANCE: Comprehensive characterization of genomic and transcriptomic alterations in breast tumors from Hispanic/Latina patients reveals distinct genetic alterations and signatures, demonstrating the importance of inclusive studies to ensure equitable care for patients. See related commentary by Schmit et al., p. 2443.


Assuntos
Neoplasias da Mama , Hispânico ou Latino , Feminino , Humanos , Neoplasias da Mama/genética , Neoplasias da Mama/patologia , Hispânico ou Latino/genética , Mutação , Transcriptoma
8.
Front Oncol ; 13: 938042, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36925912

RESUMO

Introduction: Breast cancer is a heterogeneous disease, and the distribution of the different subtypes varies by race/ethnic category in the United States and by country. Established breast cancer-associated factors impact subtype-specific risk; however, these included limited or no representation of Latin American diversity. To address this gap in knowledge, we report a description of demographic, reproductive, and lifestyle breast cancer-associated factors by age at diagnosis and disease subtype for The Peruvian Genetics and Genomics of Breast Cancer (PEGEN-BC) study. Methods: The PEGEN-BC study is a hospital-based breast cancer cohort that includes 1943 patients diagnosed at the Instituto Nacional de Enfermedades Neoplásicas in Lima, Peru. Demographic and reproductive information, as well as lifestyle exposures, were collected with a questionnaire. Clinical data, including tumor Hormone Receptor (HR) status and Human Epidermal Growth Factor Receptor 2 (HER2) status, were abstracted from electronic medical records. Differences in proportions and mean values were tested using Chi-squared and one-way ANOVA tests, respectively. Multinomial logistic regression models were used for multivariate association analyses. Results: The distribution of subtypes was 52% HR+HER2-, 19% HR+HER2+, 16% HR-HER2-, and 13% HR-HER2+. Indigenous American (IA) genetic ancestry was higher, and height was lower among individuals with the HR-HER2+ subtype (80% IA vs. 76% overall, p=0.007; 152 cm vs. 153 cm overall, p=0.032, respectively). In multivariate models, IA ancestry was associated with HR-HER2+ subtype (OR=1.38,95%CI=1.06-1.79, p=0.017) and parous women showed increased risk for HR-HER2+ (OR=2.7,95%CI=1.5-4.8, p<0.001) and HR-HER2- tumors (OR=2.4,95%CI=1.5-4.0, p<0.001) compared to nulliparous women. Multiple patient and tumor characteristics differed by age at diagnosis (<50 vs. >=50), including ancestry, region of residence, family history, height, BMI, breastfeeding, parity, and stage at diagnosis (p<0.02 for all variables). Discussion: The characteristics of the PEGEN-BC study participants do not suggest heterogeneity by tumor subtype except for IA genetic ancestry proportion, which has been previously reported. Differences by age at diagnosis were apparent and concordant with what is known about pre- and post-menopausal-specific disease risk factors. Additional studies in Peru should be developed to further understand the main contributors to the specific age of onset and molecular disease subtypes in this population and develop population-appropriate predictive models for prevention.

9.
medRxiv ; 2023 Jan 28.
Artigo em Inglês | MEDLINE | ID: mdl-36747679

RESUMO

Introduction: Breast cancer (BC) is one of the most common cancers globally. Genetic testing can facilitate screening and risk-reducing recommendations, and inform use of targeted treatments. However, genes included in testing panels are from studies of European-ancestry participants. We sequenced Hispanic/Latina (H/L) women to identify BC susceptibility genes. Methods: We conducted a pooled BC case-control analysis in H/L women from the San Francisco Bay area, Los Angeles County, and Mexico (4,178 cases and 4,344 controls). Whole exome sequencing was conducted on 1,043 cases and 1,188 controls and a targeted 857-gene panel on the remaining samples. Using ancestry-adjusted SKAT-O analyses, we tested the association of loss of function (LoF) variants with overall, estrogen receptor (ER)-positive, and ER-negative BC risk. We calculated odds ratios (OR) for BC using ancestry-adjusted logistic regression models. We also tested the association of single variants with BC risk. Results: We saw a strong association of LoF variants in FANCM with ER-negative BC (p=4.1×10-7, OR [CI]: 6.7 [2.9-15.6]) and a nominal association with overall BC risk. Among known susceptibility genes, BRCA1 (p=2.3×10-10, OR [CI]: 24.9 [6.1-102.5]), BRCA2 (p=8.4×10-10, OR [CI]: 7.0 [3.5-14.0]), and PALB2 (p=1.8×10-8, OR [CI]: 6.5 [3.2-13.1]) were strongly associated with BC. There were nominally significant associations with CHEK2, RAD51D, and TP53. Conclusion: In H/L women, LoF variants in FANCM were strongly associated with ER-negative breast cancer risk. It previously was proposed as a possible susceptibility gene for ER-negative BC, but is not routinely tested in clinical practice. Our results demonstrate that FANCM should be added to BC gene panels.

10.
Front Oncol ; 12: 940162, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36387260

RESUMO

Background: Breast cancer is the most common cancer among women in the U.S. and the leading cause of cancer death among Hispanics/Latinas (H/L). H/L are less likely than Non-H/L White (NHW) women to be diagnosed in the early stages of this disease. Approximately 5-10% of breast cancer can be attributed to inherited genetic mutations in high penetrance genes such as BRCA1/2. Women with pathogenic variants in these genes have a 40-80% lifetime risk of breast cancer. Past studies have shown that genetic counseling can help women and their families make informed decisions about genetic testing and early cancer detection or risk-reduction strategies. However, H/L are 3.9-4.8 times less likely to undergo genetic testing than NHW women. We developed a program to outreach and educate the H/L community about hereditary breast cancer, targeting monolingual Spanish-speaking individuals in California. Through this program, we have assessed cancer screening behavior and identified women who might benefit from genetic counseling in a population that is usually excluded from cancer research and care. Materials and Methods: The "Tu Historia Cuenta" program is a promotores-based virtual outreach and education program including the cities of San Francisco, Sacramento, and Los Angeles. Participants responded to three surveys: a demographic survey, a breast cancer family history survey, and a feedback survey. Survey responses were described for participants and compared by area where the program took place using chi-square, Fisher exact tests, and t tests. Multinomial logistic regression models were used for multivariate analyses. Results and Conclusion: We enrolled 1042 women, 892 completed the cancer family history survey and 62 (7%) provided responses compatible with referral to genetic counseling. We identified 272 women (42.8% ages 40 to 74 years) who were due for mammograms, 250 women (24.7% ages 25 to 65 years) due for Papanicolaou test, and 189 women (71.6% ages 50+) due for colorectal cancer screening. These results highlight the need of additional support for programs that spread awareness about cancer risk and facilitate access to resources, specifically within the H/L community.

11.
BMC Womens Health ; 22(1): 336, 2022 08 08.
Artigo em Inglês | MEDLINE | ID: mdl-35941639

RESUMO

BACKGROUND: Awareness about hereditary breast cancer and the preventative steps to minimize disease risk is lower in Hispanic/Latina individuals than non-Hispanic White women in the United States. For this reason, we developed a promotor-based hereditary breast cancer education and risk identification program for self-identified Hispanic/Latina women, which included training promotores in basic genetics and hereditary breast cancer. This study explored promotores' experiences receiving training and participating in virtual practice sessions as well as changes in knowledge about hereditary breast cancer. METHODS: A total of ten promotores underwent a two-week basic training led by the promotores organization and an eight-hour in person hereditary breast cancer training workshop. Demographic information along with pre- and post-training surveys were completed by ten promotores who participated in the training workshop. Surveys were given to determine changes in knowledge of hereditary breast cancer and genetics. Of the ten promotores, two were selected to lead community education sessions and participated in 6 semi-structured interviews. All interviews and practice sessions were conducted using a virtual platform. RESULTS: The data revealed that after the 8-h workshop and practice sessions, promotores felt confident about their ability to conduct virtual education sessions with the community. Interviews identified key facilitators to success such as a supportive environment, practice presentations, and personal motivation. Learning the online platform was considered the biggest challenge by the promotores, as opposed to learning complex genetics topics. CONCLUSIONS: These results provide further evidence supporting promotores' willingness and ability to provide health education on relatively complex topics. It also offers insight into the challenges of presenting information to vulnerable populations using an online platform and the additional support that is required to ensure a positive outcome.


Assuntos
Neoplasias da Mama , Agentes Comunitários de Saúde , Neoplasias da Mama/genética , California , Feminino , Educação em Saúde/métodos , Hispânico ou Latino , Humanos , América Latina
12.
Front Oncol ; 12: 883200, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35875145

RESUMO

Background: Cancer is the leading cause of death among Latinos, the largest minority population in the United States (US). To address cancer challenges experienced by Latinos, we conducted a catchment area population assessment (CAPA) using validated questions from the National Cancer Institute (NCI) population health assessment supplement at our NCI-designated cancer center in California. Methods: A mixed-methods CAPA was administered by bilingual-bicultural staff, with a focus on understanding the differences between foreign-born and US-born Latinos. Results: 255 Latinos responded to the survey conducted between August 2019 and May 2020. Most respondents were foreign-born (63.9%), female (78.2%), and monolingual Spanish speakers (63.2%). Results showed that compared to US-born Latinos, foreign-born individuals were older, had lower educational attainment, were most likely to be monolingual Spanish speakers, were low-income, and were more likely to be uninsured. Foreign-born Latinos had lower levels of alcohol consumption and higher consumption of fruits and vegetables. The rate of preventive cancer screenings for breast, cervical and colorectal cancer did not differ by birthplace, although a low fraction (35.3%) of foreign-born Latinas who were up-to-date compared to US-born Latinas (83.3%) with colorectal cancer screening was observed. Time since the last routine check-up for all preventable cancers (cervical p=0.0002, breast p=0.0039, and colorectal p=0.0196) is significantly associated with being up to date with cancer screening. Individuals who had a check-up of two or more years ago are 84% less likely to be up to date with pap smears than those who had a check-up within the year (p=0.0060). Individuals without health insurance are 94% less likely to be up to date with mammograms and colonoscopy/FIT tests (p=0.0016 and p=0.0133, respectively) than those who are insured. There is no significant association between screening and nativity. Conclusions: Considerable differences in socio-economic and environmental determinants of health and colorectal cancer screening rates were observed between US-born and foreign-born Latinos. The present study represents the foundation for future targeted intervention among immigrant populations at our cancer center's catchment area.

13.
Mol Biol Evol ; 39(8)2022 08 03.
Artigo em Inglês | MEDLINE | ID: mdl-35860855

RESUMO

Peru hosts extremely diverse ecosystems which can be broadly classified into the following three major ecoregions: the Pacific desert coast, the Andean highlands, and the Amazon rainforest. Since its initial peopling approximately 12,000 years ago, the populations inhabiting such ecoregions might have differentially adapted to their contrasting environmental pressures. Previous studies have described several candidate genes underlying adaptation to hypobaric hypoxia among Andean highlanders. However, the adaptive genetic diversity of coastal and rainforest populations has been less studied. Here, we gathered genome-wide single-nucleotide polymorphism-array data from 286 Peruvians living across the three ecoregions and analyzed signals of recent positive selection through population differentiation and haplotype-based selection scans. Among highland populations, we identify candidate genes related to cardiovascular function (TLL1, DUSP27, TBX5, PLXNA4, SGCD), to the Hypoxia-Inducible Factor pathway (TGFA, APIP), to skin pigmentation (MITF), as well as to glucose (GLIS3) and glycogen metabolism (PPP1R3C, GANC). In contrast, most signatures of adaptation in coastal and rainforest populations comprise candidate genes related to the immune system (including SIGLEC8, TRIM21, CD44, and ICAM1 in the coast; CBLB and PRDM1 in the rainforest; and BRD2, HLA-DOA, HLA-DPA1 regions in both), possibly as a result of strong pathogen-driven selection. This study identifies candidate genes related to human adaptation to the diverse environments of South America.


Assuntos
Altitude , Ecossistema , Adaptação Fisiológica/genética , Humanos , Hipóxia/genética , Peru , Polimorfismo de Nucleotídeo Único , Seleção Genética , Metaloproteases Semelhantes a Toloide/genética
14.
Elife ; 112022 07 07.
Artigo em Inglês | MEDLINE | ID: mdl-35796544

RESUMO

The National Institute on Minority Health and Health Disparities (NIMHD) has developed a framework to guide and orient research into health disparities and minority health. The framework depicts different domains of influence (such as biological and behavioral) and different levels of influence (such as individual and interpersonal). Here, influenced by the "One Health" approach, we propose adding two new levels of influence - interspecies and planetary - to this framework to reflect the interconnected nature of human, animal, and environmental health. Extending the framework in this way will help researchers to create new avenues of inquiry and encourage multidisciplinary collaborations. We then use the One Health approach to discuss how the COVID-19 pandemic has exacerbated health disparities, and show how the expanded framework can be applied to research into health disparities related to antimicrobial resistance and obesity.


Assuntos
COVID-19 , Saúde das Minorias , COVID-19/epidemiologia , Humanos , Grupos Minoritários , Pandemias , Estados Unidos
15.
Cancer Epidemiol Biomarkers Prev ; 31(8): 1602-1609, 2022 08 02.
Artigo em Inglês | MEDLINE | ID: mdl-35654312

RESUMO

BACKGROUND: Breast cancer incidence in the United States is lower in Hispanic/Latina (H/L) compared with African American/Black or Non-Hispanic White women. An Indigenous American breast cancer-protective germline variant (rs140068132) has been reported near the estrogen receptor 1 gene. This study tests the association of rs140068132 and other polymorphisms in the 6q25 region with subtype-specific breast cancer risk in H/Ls of high Indigenous American ancestry. METHODS: Genotypes were obtained for 5,094 Peruvian women with (1,755) and without (3,337) breast cancer. Associations between genotype and overall and subtype-specific risk for the protective variant were tested using logistic regression models and conditional analyses, including other risk-associated polymorphisms in the region. RESULTS: We replicated the reported association between rs140068132 and breast cancer risk overall [odds ratio (OR), 0.53; 95% confidence interval (CI), 0.47-0.59], as well as the lower odds of developing hormone receptor negative (HR-) versus HR+ disease (OR, 0.77; 95% CI, 0.61-0.97). Models, including HER2, showed further heterogeneity with reduced odds for HR+HER2+ (OR, 0.68; 95% CI, 0.51-0.92), HR-HER2+ (OR, 0.63; 95% CI, 0.44-0.90) and HR-HER2- (OR, 0.77; 95% CI, 0.56-1.05) compared with HR+HER2-. Inclusion of other risk-associated variants did not change these observations. CONCLUSIONS: The rs140068132 polymorphism is associated with decreased risk of breast cancer in Peruvians and is more protective against HR- and HER2+ diseases independently of other breast cancer-associated variants in the 6q25 region. IMPACT: These results could inform functional analyses to understand the mechanism by which rs140068132-G reduces risk of breast cancer development in a subtype-specific manner. They also illustrate the importance of including diverse individuals in genetic studies.


Assuntos
Neoplasias da Mama , Neoplasias da Mama/epidemiologia , Neoplasias da Mama/etnologia , Neoplasias da Mama/genética , Cromossomos Humanos Par 6 , Feminino , Hispânico ou Latino , Humanos , Modelos Logísticos , Peru/epidemiologia , Receptor ErbB-2/genética , Receptores de Estrogênio/genética , Receptores de Progesterona/genética
16.
Front Oncol ; 12: 835626, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35433488

RESUMO

Purposes: Most molecular-based published studies on breast cancer do not adequately represent the unique and diverse genetic admixture of the Latin American population. Searching for similarities and differences in molecular pathways associated with these tumors and evaluating its impact on prognosis may help to select better therapeutic approaches. Patients and Methods: We collected clinical, pathological, and transcriptomic data of a multi-country Latin American cohort of 1,071 stage II-III breast cancer patients of the Molecular Profile of Breast Cancer Study (MPBCS) cohort. The 5-year prognostic ability of intrinsic (transcriptomic-based) PAM50 and immunohistochemical classifications, both at the cancer-specific (OSC) and disease-free survival (DFS) stages, was compared. Pathway analyses (GSEA, GSVA and MetaCore) were performed to explore differences among intrinsic subtypes. Results: PAM50 classification of the MPBCS cohort defined 42·6% of tumors as LumA, 21·3% as LumB, 13·3% as HER2E and 16·6% as Basal. Both OSC and DFS for LumA tumors were significantly better than for other subtypes, while Basal tumors had the worst prognosis. While the prognostic power of traditional subtypes calculated with hormone receptors (HR), HER2 and Ki67 determinations showed an acceptable performance, PAM50-derived risk of recurrence best discriminated low, intermediate and high-risk groups. Transcriptomic pathway analysis showed high proliferation (i.e. cell cycle control and DNA damage repair) associated with LumB, HER2E and Basal tumors, and a strong dependency on the estrogen pathway for LumA. Terms related to both innate and adaptive immune responses were seen predominantly upregulated in Basal tumors, and, to a lesser extent, in HER2E, with respect to LumA and B tumors. Conclusions: This is the first study that assesses molecular features at the transcriptomic level in a multicountry Latin American breast cancer patient cohort. Hormone-related and proliferation pathways that predominate in PAM50 and other breast cancer molecular classifications are also the main tumor-driving mechanisms in this cohort and have prognostic power. The immune-related features seen in the most aggressive subtypes may pave the way for therapeutic approaches not yet disseminated in Latin America. Clinical Trial Registration: ClinicalTrials.gov (Identifier: NCT02326857).

17.
Cancer Epidemiol Biomarkers Prev ; 31(5): 932-941, 2022 05 04.
Artigo em Inglês | MEDLINE | ID: mdl-35247883

RESUMO

The Hispanic/Latino(x) population (H/L) in the United States of America is heterogeneous and fast growing. Cancer is the number one cause of death among H/Ls, accounting for 21% of deaths. Whereas for the most common cancers, incidence rates are lower in H/Ls compared with non-H/L White (NHW) individuals, H/Ls have a higher incidence of liver, stomach, cervical, penile, and gallbladder cancers. H/L patients tend to be diagnosed at more advanced stages for breast, colorectal, prostate, and lung cancers, and melanoma compared with NHW individuals. Etiologic and cancer outcomes research among H/Ls lags other populations. In this review, we provide a summary of challenges, opportunities, and research priorities related to cancer etiology, cancer outcomes, and survivorship to make progress in addressing scientific gaps. Briefly, we prioritize the need for more research on determinants of obesity, nonalcoholic fatty liver disease and its progression to liver cancer, stomach and gallbladder cancers, and pediatric acute lymphoblastic leukemia. We emphasize the need to improve cancer screening, early detection of cancer, and survivorship care. We highlight critical resources needed to make progress in cancer epidemiologic studies among H/L populations, including the importance of training the next generation of cancer epidemiologists conducting research in H/Ls.


Assuntos
Neoplasias da Vesícula Biliar , Neoplasias Hepáticas , Melanoma , Neoplasias , Criança , Hispânico ou Latino , Humanos , Incidência , Masculino , Neoplasias/epidemiologia , Sobrevivência , Estados Unidos/epidemiologia
18.
Front Oncol ; 12: 989761, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36620598

RESUMO

Background: Our previous study reported higher mRNA levels of the human epidermal growth factor receptor 2 (HER2)-amplicon genes ERBB2 and GRB7 in estrogen receptor (ER)-positive breast cancer patients with relatively high Indigenous American (IA) ancestry from Colombia. Even though the protein expression of HER2 and GRB7 is highly correlated, they may also express independently, an event that could change the patients' prognosis. In this study, we aimed to explore the differences in ER, HER2 and GRB7 protein expression according to genetic ancestry, to further assess the clinical implications of this association. Methods: We estimated genetic ancestry from non-tumoral breast tissue DNA and assessed tumoral protein expression of ER, HER2, and GRB7 by immunohistochemistry in a cohort of Colombian patients from different health institutions. We used binomial and multinomial logistic regression models to test the association between genetic ancestry and protein expression. Kaplan-Meier and log-rank tests were used to evaluate the effect of HER2/GRB7 co-expression on patients' survival. Results: Our results show that patients with higher IA ancestry have higher odds of having HER2+/GRB7- breast tumors, compared to the HER2-/GRB7- subtype, and this association seems to be stronger among ER-positive tumors (ER+/HER2+/GRB7-: OR=3.04, 95% CI, 1.47-6.37, p<0.05). However, in the multivariate model this association was attenuated (OR=1.80, 95% CI, 0.72-4.44, p=0.19). On the other hand, it was observed that having a higher European ancestry patients presented lower odds of ER+/HER2+/GRB7- breast tumors, this association remained significant in the multivariate model (OR=0.36, 95% CI, 0.13 - 0.93, p= 0.0395). The survival analysis according to HER2/GRB7 co-expression did not show statistically significant differences in the overall survival and recurrence-free survival. Conclusions: Our results suggest that Colombian patients with higher IA ancestry and a lower European fraction have higher odds of ER+/HER2+/GRB7- tumors compared to ER+/HER2-/GRB7- disease. However, this association does not seem to be associated with patients' overall or recurrence-free survival.

20.
Curr Breast Cancer Rep ; 13(3): 110-112, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34394841

RESUMO

Purpose of Review: The emergency medicine and critical care needs of the COVID-19 pandemic forced a sudden and dramatic disruption of cancer screening and treatment programs in the USA during the winter and spring of 2020. This review commentary addresses the impact of the pandemic on racial/ethnic minorities such as African Americans and Hispanic-Latina Americans, with a focus on factors related to breast cancer. Recent Findings: African Americans and Hispanic-Latina Americans experienced disproportionately higher morbidity and mortality from COVID-19; many of the same socioeconomic and tumor biology/genetic factors that explain breast cancer disparities are likely to account for COVID-19 outcome disparities. Summary: The breast cancer clinical and research community should partner with public health experts to ensure participation of diverse patients in COVID-19 treatment trials and vaccine programs and to overcome COVID-19-related breast health management delays that are likely to have been magnified among African Americans and Hispanic-Latina Americans.

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