121 results on '"Valerie McCormack"'
Search Results
2. Reproductive history and breast cancer survival: Findings from the African breast cancer—Disparities in outcomes cohort and implications of Africa's fertility transition on breast cancer prognosis
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Pauline Boucheron, Angelica Anele, Awa U. Offiah, Annelle Zietsman, Moses Galukande, Groesbeck Parham, Leeya F. Pinder, Benjamin O. Anderson, Milena Foerster, Joachim Schüz, Isabel dos ‐Santos‐Silva, and Valerie McCormack
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Cancer Research ,Oncology ,Article - Abstract
Reproductive characteristics are known risk factors for breast cancer but, other than recent birth, their role as prognostic factors is less clear, and has not been studied in Sub-Saharan Africa (SSA). In this setting, we examined whether reproductive factors independently influence breast cancer survival in a subset of the African Breast Cancer – Disparities in Outcomes cohort study. In 1485 women with incident breast cancer recruited between 2014 and 2017, we examined birth cohort changes in reproductive factors, and used Cox models to examine whether reproductive characteristics were associated with all-cause mortality after adjusting for confounders (age, stage, treatment, HIV, and social factors). Four years after diagnosis, 822 (56%) women had died. Median parity was 4 (IQR=2, 6) and 209 (28%) of premenopausal women had had a recent birth (less than three years prior to cancer diagnosis). Each pregnancy was associated with a 5% increase (95% CI: 2%, 8%) in mortality rates, which held among postmenopausal women (5%, (1%-9%)). Pre-menopausal women with a recent birth had 52% (20%, 92%) higher mortality rates. Fertility trends by birth cohort showed declining parity, increasing age at first birth and declining age at last birth, however the impact of these population-level changes on future average survival was predicted to be very small (
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- 2023
3. Global and regional estimates of orphans attributed to maternal cancer mortality in 2020
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Florence Guida, Rachel Kidman, Jacques Ferlay, Joachim Schüz, Isabelle Soerjomataram, Benda Kithaka, Ophira Ginsburg, Raymond B. Mailhot Vega, Moses Galukande, Groesbeck Parham, Salvatore Vaccarella, Karen Canfell, Andre M. Ilbawi, Benjamin O. Anderson, Freddie Bray, Isabel dos-Santos-Silva, and Valerie McCormack
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General Medicine ,General Biochemistry, Genetics and Molecular Biology - Abstract
Despite women being disproportionally affected by cancer deaths at young ages, there are no global estimates of the resulting maternal orphans, who experience health and education disadvantages throughout their lives. We estimated the number of children who became maternal orphans in 2020 due to their mother dying from cancer in that year, for 185 countries worldwide and by cause of cancer-related death. Female cancer deaths—by country, cancer type and age (derived from GLOBOCAN estimates)—were multiplied by each woman’s estimated number of children under the age of 18 years at the time of her death (fertility data were derived from United Nations World Population Prospects for birth cohort), accounting for child mortality and parity-cancer risk associations. Globally, there were 1,047,000 such orphans. Over half of these were orphans due to maternal deaths from breast (258,000, 25%), cervix (210,000, 20%) and upper-gastrointestinal cancers (136,000, 13%), and most occurred in Asia (48%: India 15%, China 10%, rest of Asia 23%) and Africa (35%). Globally, there were 40 new maternal orphans due to cancer per 100,000 children, with a declining trend with a higher Human Development Index (range: 121 in Malawi to 15 in Malta). An estimated 7 million children were prevalent maternal orphans due to cancer in mid-2020. Accelerating the implementation of the World Health Organization’s cervical and breast cancer initiatives has the potential to avert not only millions of preventable female cancer deaths but also the associated, often-overlooked, intergenerational consequences of these deaths.
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- 2022
4. Population-based investigation of common and deviating patterns of gastric cancer and oesophageal cancer incidence across populations and time
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Mengmeng Li, Jin Young Park, Mahdi Sheikh, Violet Kayamba, Harriet Rumgay, Mazda Jenab, Clement Tetteh Narh, Behnoush Abedi-Ardekani, Eileen Morgan, Catherine de Martel, Valerie McCormack, and Melina Arnold
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Gastroenterology - Abstract
BackgroundThe subtypes of gastric cancer (GC) and oesophageal cancer (EC) manifest distinct epidemiological profiles. Here, we aim to examine correlations in their incidence rates and to compare their temporal changes globally, both overall and by subtype.MethodsLong-term incidence data were obtained from population-based registries available from the Cancer Incidence in Five Continents series. Variation in the occurrence of EC and GC (overall and by subtype) was assessed using the GC:EC ratio of sex-specific age-standardised rates (ASR) in 2008–2012. Average annual per cent changes were estimated to assess temporal trends during 1998–2012.ResultsASRs for GC and EC varied remarkably across and within world regions. In the countries evaluated, the GC:EC ratio in men exceeded 10 in several South American countries, Algeria and Republic of Korea, while EC dominated in most sub-Saharan African countries. High rates of both cardia gastric cancer and oesophageal squamous cell carcinoma (ESCC) were observed in several Asian populations. Non-cardia gastric cancer rates correlated positively with ESCC rates (r=0.60) and negatively with EAC (r=−0.79). For the time trends, while GC incidence has been uniformly decreasing by on average 2%–3% annually over 1998–2012 in most countries, trends for EC depend strongly on histology, with several but not all countries experiencing increases in EAC and decreases in ESCC.ConclusionsCorrelations between GC and EC incidence rates across populations are positive or inverse depending on the GC subsite and EC subtype. Multisite studies that include a combination of populations whose incidence rates follow and deviate from these patterns may be aetiologically informative.
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- 2022
5. A very-hot food and beverage thermal exposure index and esophageal cancer risk in Malawi and Tanzania: findings from the ESCCAPE case–control studies
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Gwinyai Masukume, Blandina T. Mmbaga, Charles P. Dzamalala, Yohannie B. Mlombe, Peter Finch, Gissela Nyakunga-Maro, Alex Mremi, Daniel R. S. Middleton, Clement T. Narh, Steady J. D. Chasimpha, Behnoush Abedi-Ardekani, Diana Menya, Joachim Schüz, and Valerie McCormack
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Cancer Research ,Oncology - Abstract
Background Consumption of very-hot beverages/food is a probable carcinogen. In East Africa, we investigated esophageal squamous cell carcinoma (ESCC) risk in relation to four thermal exposure metrics separately and in a combined score. Methods From the ESCCAPE case–control studies in Blantyre, Malawi (2017-20) and Kilimanjaro, Tanzania (2015-19), we used logistic regression models adjusted for country, age, sex, alcohol and tobacco, to estimate odds ratios (ORs) and 95% confidence intervals (CIs) for self-reported thermal exposures whilst consuming tea, coffee and/or porridge. Results The study included 849 cases and 906 controls. All metrics were positively associated with ESCC: temperature of drink/food (OR 1.92 (95% CI: 1.50, 2.46) for ‘very hot’ vs ‘hot’), waiting time before drinking/eating (1.76 (1.37, 2.26) for Conclusions Thermal exposure metrics were strongly associated with ESCC risk. Avoidance of very-hot food/beverage consumption may contribute to the prevention of ESCC in East Africa.
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- 2022
6. Treatment guideline concordance, initiation, and abandonment in patients with non-metastatic breast cancer from the African Breast Cancer–Disparities in Outcomes (ABC-DO) cohort in sub-Saharan Africa: a prospective cohort study
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Milena Foerster, Valerie McCormack, Benjamin O Anderson, Pauline Boucheron, Annelle Zietsman, Herbert Cubasch, Maureen Joffe, Angelica Anele, Shadrach Offiah, Moses Galukande, Groesbeck Parham, Leeya F Pinder, Ophira Ginsburg, Joachim Schüz, Isabel dos-Santos-Silva, and Eva J Kantelhardt
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Oncology - Abstract
BACKGROUND: Comprehensive breast cancer management is essential to achieve high breast cancer survival; however, detailed reports of the treatment regimens received by patients are scarce in sub-Saharan Africa where survival is low. We aimed to examine treatment initiation, guideline concordance, and abandonment in patients with non-metastatic breast cancer in sub-Saharan Africa from the African Breast Cancer-Disparities in Outcomes (ABC-DO) prospective cohort. METHODS: The ABC-DO prospective cohort study recruited women (aged ≥18 years) with newly diagnosed invasive breast cancer in eight hospitals across five sub-Saharan African countries (Namibia, Nigeria, Uganda, South Africa, and Zambia). We analysed treatments received by women who were classified as non-metastatic (M0) at the initial presentation. Data on surgery, radiotherapy, and systemic therapies were obtained from medical records and a self-reported follow-up questionnaire at 6 months after the diagnosis, follow-up calls every 3 months, and a baseline questionnaire. Initiation, completion, and abandonment of treatment modalities and combined therapy regimens were examined overall, by country-specific groups, and by clinical factors relevant for guideline-based treatment. FINDINGS: Of 2313 women recruited into the ABC-DO study between Sept 10, 2014, and Dec 31, 2017, 2226 had histologically or clinically confirmed breast cancer. Of these 2226 women, 510 were excluded from the present analysis because 378 had metastatic disease, 37 were prevalent cases (defined as those previously diagnosed with breast cancer >2 years before baseline), 82 had unknown TNM stage, and 13 were White or Asian women in South Africa (number was too small for analysis). After a median follow-up of 5·2 years (IQR 4·6-5·9), 1163 (68%) of 1716 women underwent breast cancer surgery. Surgery and systemic therapy (ie, multimodality treatment) with radiotherapy was initiated in 370 (36%) of 1028 women with localised tumours versus 156 (23%) of 688 women with locally advanced tumours, whereas multimodality treatment without radiotherapy was initiated in 386 (38%) versus 167 (24%) women, respectively. Of 1530 patients requiring chemotherapy (which excludes 105 who died within 6 months after baseline), 1013 (66%) initiated treatment of neoadjuvant chemotherapy or surgery within 3 months after baseline, which was adequately completed by 359 (35%) of 1013 women, marginally completed by 284 (28%), abandoned by 200 (20%), and unknown in 151 (15%). 19 (2%) women died within 6 months after chemotherapy initiation. Of 1375 women in whom endocrine therapy was indicated, this treatment was initiated in 920, and lasted at least 3 years in 367 (40%) women. Treatment disparities between country-specific groups were substantial for all therapy regimens. INTERPRETATION: A high proportion of patients with non-metastatic breast cancer did not initiate, did not fully complete, or abandoned treatment with surgery, systemic therapy, radiotherapy, or an appropriate combination of these, highlighting the need for improved treatment access and completion in sub-Saharan Africa to potentially prevent premature breast cancer deaths. FUNDING: National Institutes of Health (National Cancer Institute), Susan G Komen, and the International Agency for Research on Cancer.
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- 2022
7. Regional variation in the tumor microenvironment, immune escape and prognostic factors in breast cancer in sub-Saharan Africa
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Marcus Bauer, Martina Vetter, Kathrin Stückrath, Meron Yohannes, Zelalem Desalegn, Tewodros Yalew, Yonas Bekuretsion, Tariku W. Kenea, Maureen Joffe, Eunice J. Van Den Berg, Julien Ilunga. Nikulu, Kamaté Bakarou, Shyam S. Manraj, Olufemi J. Ogunbiyi, Ima-Obong Ekanem, Festus Igbinoba, Mohenou Diomande, Clement Adebamowo, Charles P. Dzamalala, Angelica A. Anele, Annelle Zietsman, Moses Galukande, Milena Foerster, Isabel dos-Santos-Silva, Biying Liu, Pablo Santos, Ahmedin Jemal, Tamrat Abebe, Claudia Wickenhauser, Barbara Seliger, Valerie McCormack, and Eva J. Kantelhardt
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Cancer Research ,Immunology - Abstract
The low overall survival rates of breast cancer (BC) patients in sub-Saharan Africa (SSA) are driven by regionally differing tumor biology, advanced tumor stages at diagnosis and limited access to therapy. However, it is not known whether regional differences in the composition of the tumor microenvironment (TME) exist and affect patients’ prognosis. In this international, multicentre cohort study, 1,237 formalin-fixed, paraffin-embedded BC samples, including samples of the ‘African Breast Cancer-Disparities in Outcomes (ABC-DO) Study’, were analyzed. The immune cell phenotypes, their spatial distribution in the TME and immune escape mechanisms of BC samples from SSA and Germany (n=117) were investigated using histomorphology, conventional and multiplex immunohistochemistry (IHC), and RNA expression analysis. The data revealed no regional differences in the number of tumor-infiltrating lymphocytes (TILs) in the 1,237 SSA BC samples, while the distribution of TILs in different BC IHC subtypes showed regional diversity, particularly when compared to German samples. Higher TIL densities were associated with better survival in the SSA cohort (n=400), but regional differences concerning the predictive value of TILs existed. High numbers of CD163+ macrophages and CD3+CD8+ T cells accompanied by reduced cytotoxicity, altered IL10 and IFNγ levels and downregulation of MHC class I components were predominantly detected in BC samples from Western SSA. Features of non-immunogenic BC phenotypes were associated with reduced patient survival (n=131). We therefore conclude that regional diversity in the distribution of BC subtypes, TME composition and immune escape mechanisms should be considered for therapy decisions in SSA and the design of personalized therapies.
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- 2023
8. Survival Disparities Between Patients with Breast Cancer With and Without HIV: A Research Framework
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Steady Chasimpha, Isabel dos Santos Silva, Yehoda M. Martei, Surbhi Grover, Herbert Cubasch, and Valerie McCormack
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Cancer Research ,Oncology - Published
- 2023
9. Data from Racial Comparison of Receptor-Defined Breast Cancer in Southern African Women: Subtype Prevalence and Age–Incidence Analysis of Nationwide Cancer Registry Data
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Valerie McCormack, Danuta Kielkowski, Joachim Schüz, Patricia Kellett, Herbert Cubasch, Annelle Zietsman, Raquel Duarte, and Caroline Dickens
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Background: Receptor-defined breast cancer proportions vary across Africa. They have important implications for survival prospects and research priorities.Methods: We studied estrogen receptor (ER), progesterone receptor (PR), and HER2 receptor statuses in two multiracial Southern African countries with routine diagnostic immunohistochemistry. A total of 12,361 women with histologically confirmed breast cancer diagnosed at age ≥20 years during (i) 2009–2011 from South Africa's national cancer registry (public sector) and (ii) 2011–2013 from Namibia's only cancer hospital were included. Crude, age, and age + laboratory–adjusted ORs of receptor status were analyzed using logistic regression, and age–incidence curves were analyzed using Poisson regression.Results: A total of 10,047 (81%) women had known ER status. Ranking of subtypes was consistent across races: ER+/PR+HER2− was most common (race-specific percentage range, 54.6%–64.8%), followed by triple-negative (17.4%–21.9%), ER+/PR+HER2+ (9.6%–13.9%), and ER−PR−HER2+ (7.8%–10.9%). Percentages in black versus white women were 33.8% [95% confidence (CI), 32.5–35.0] versus 26.0% (24.0–27.9) ER−; 20.9% (19.7–22.1) versus 17.5% (15.4–19.6) triple-negative; and 10.7% (9.8–11.6) versus 7.8% (6.3–9.3) ER−PR−HER2+. Indian/Asian and mixed-ancestry women had intermediate values. Age–incidence curves had similar shapes across races: rates increased by 12.7% per year (12.2–13.1) across ER subtypes under the age of 50 years, and thereafter slowed for ER+ (1.95%) and plateaued for ER− disease (−0.1%).Conclusions: ER+ breast cancer dominates in all Southern African races, but black women have a modest excess of aggressive subtypes.Impact: On the basis of the predominant receptor-defined breast tumors in Southern Africa, improving survival for the growing breast cancer burden should be achievable through earlier diagnosis and appropriate treatment. Cancer Epidemiol Biomarkers Prev; 23(11); 2311–21. ©2014 AACR.
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- 2023
10. Data from Genome-Wide DNA Methylation Profiling of Esophageal Squamous Cell Carcinoma from Global High-Incidence Regions Identifies Crucial Genes and Potential Cancer Markers
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Zdenko Herceg, Luis Felipe Ribeiro Pinto, M. Iqbal Parker, Valerie McCormack, Joachim Schüz, Maria Leon Roux, Akram Ghantous, Florence Le Calvez-Kelm, Daniel R.S. Middleton, Nitin Gangane, Mona Ellaithi, Nagla Gasmelseed, Reza Malekzadeh, Ramin Shakeri, Rui M. Henrique, Carmen Jerónimo, Vera Miranda-Gonçalves, Abraham Aseffa, Mathewos Assefa, Charles P. Dzamalala, Diana Menya, Christine Carreira, Behnoush Abedi-Ardekani, Anne-Claire Boisson, Bruna Pereira Sorroche, Cyrille Cuenin, Ruhina Shirin Laskar, Rita Khoueiry, Sheila C. Soares Lima, and Fazlur Rahman Talukdar
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Epigenetic mechanisms such as aberrant DNA methylation (DNAme) are known to drive esophageal squamous cell carcinoma (ESCC), yet they remain poorly understood. Here, we studied tumor-specific DNAme in ESCC cases from nine high-incidence countries of Africa, Asia, and South America. Infinium MethylationEPIC array was performed on 108 tumors and 51 normal tissues adjacent to the tumors (NAT) in the discovery phase, and targeted pyrosequencing was performed on 132 tumors and 36 NAT in the replication phase. Top genes for replication were prioritized by weighting methylation results using RNA-sequencing data from The Cancer Genome Atlas and GTEx and validated by qPCR. Methylome analysis comparing tumor and NAT identified 6,796 differentially methylated positions (DMP) and 866 differential methylated regions (DMR), with a 30% methylation (Δβ) difference. The majority of identified DMPs and DMRs were hypermethylated in tumors, particularly in promoters and gene-body regions of genes involved in transcription activation. The top three prioritized genes for replication, PAX9, SIM2, and THSD4, had similar methylation differences in the discovery and replication sets. These genes were exclusively expressed in normal esophageal tissues in GTEx and downregulated in tumors. The specificity and sensitivity of these DNAme events in discriminating tumors from NAT were assessed. Our study identified novel, robust, and crucial tumor-specific DNAme events in ESCC tumors across several high-incidence populations of the world. Methylome changes identified in this study may serve as potential targets for biomarker discovery and warrant further functional characterization.Significance:This largest genome-wide DNA methylation study on ESCC from high-incidence populations of the world identifies functionally relevant and robust DNAme events that could serve as potential tumor-specific markers.
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- 2023
11. Figures from Genome-Wide DNA Methylation Profiling of Esophageal Squamous Cell Carcinoma from Global High-Incidence Regions Identifies Crucial Genes and Potential Cancer Markers
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Zdenko Herceg, Luis Felipe Ribeiro Pinto, M. Iqbal Parker, Valerie McCormack, Joachim Schüz, Maria Leon Roux, Akram Ghantous, Florence Le Calvez-Kelm, Daniel R.S. Middleton, Nitin Gangane, Mona Ellaithi, Nagla Gasmelseed, Reza Malekzadeh, Ramin Shakeri, Rui M. Henrique, Carmen Jerónimo, Vera Miranda-Gonçalves, Abraham Aseffa, Mathewos Assefa, Charles P. Dzamalala, Diana Menya, Christine Carreira, Behnoush Abedi-Ardekani, Anne-Claire Boisson, Bruna Pereira Sorroche, Cyrille Cuenin, Ruhina Shirin Laskar, Rita Khoueiry, Sheila C. Soares Lima, and Fazlur Rahman Talukdar
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7 supplementary figures
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- 2023
12. Supplementary Data from Genome-Wide DNA Methylation Profiling of Esophageal Squamous Cell Carcinoma from Global High-Incidence Regions Identifies Crucial Genes and Potential Cancer Markers
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Zdenko Herceg, Luis Felipe Ribeiro Pinto, M. Iqbal Parker, Valerie McCormack, Joachim Schüz, Maria Leon Roux, Akram Ghantous, Florence Le Calvez-Kelm, Daniel R.S. Middleton, Nitin Gangane, Mona Ellaithi, Nagla Gasmelseed, Reza Malekzadeh, Ramin Shakeri, Rui M. Henrique, Carmen Jerónimo, Vera Miranda-Gonçalves, Abraham Aseffa, Mathewos Assefa, Charles P. Dzamalala, Diana Menya, Christine Carreira, Behnoush Abedi-Ardekani, Anne-Claire Boisson, Bruna Pereira Sorroche, Cyrille Cuenin, Ruhina Shirin Laskar, Rita Khoueiry, Sheila C. Soares Lima, and Fazlur Rahman Talukdar
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16 supplementary tables
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- 2023
13. Supplementary Methods, Tables 1 - 2, Figures 1 - 2 from Racial Comparison of Receptor-Defined Breast Cancer in Southern African Women: Subtype Prevalence and Age–Incidence Analysis of Nationwide Cancer Registry Data
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Valerie McCormack, Danuta Kielkowski, Joachim Schüz, Patricia Kellett, Herbert Cubasch, Annelle Zietsman, Raquel Duarte, and Caroline Dickens
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The supplementary material includes more detailed descriptions of the methodology, in particular details of the receptor-extraction algorithm and additional statistical methods. Supplementary results include Supplementary Table S1.1: Namibian and NHLS laboratories (SA) where ER, PR and HER2 immunohistochemistry is performed. Supplementary Table S2.1: Characteristics of 12361 histologically-confirmed breast cancer patients; Supplementary Table S2.2: Characteristics of women with missing ER status; Supplementary Table S2.3: Breast cancer subtype distribution by race; Supplementary Figure S1.1: Annual number of public sector breast cancers in women in SA in 2009-10 as a percentage of annual number of total cases in 2006; Supplementary Figure S2.1: Age-specific percentages of ER�, PR� and HER2� breast cancer by race; Supplementary Figure S2.2: Laboratory-specific receptor-prevalences by race and Supplementary Figure S2.3: Laboratory-specific ORs for ER, PR and HER2 associated with race.
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- 2023
14. Disparities in breast cancer survival between women with and without HIV across sub-Saharan Africa (ABC-DO): a prospective, cohort study
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Steady Chasimpha, Valerie McCormack, Herbert Cubasch, Maureen Joffe, Annelle Zietsman, Moses Galukande, Groesbeck Parham, Leeya F Pinder, Angelica Anele, Charles A Adisa, Awa Ukonye Offiah, Benjamin O Anderson, Pauline Boucheron, Milena Foerster, Joachim Schüz, and Isabel dos-Santos-Silva
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Adult ,Cohort Studies ,South Africa ,Infectious Diseases ,Adolescent ,Epidemiology ,Virology ,Immunology ,Humans ,Breast Neoplasms ,Female ,HIV Infections ,Prospective Studies - Abstract
BACKGROUND: Studies have shown increased mortality among women living with HIV diagnosed with breast cancer compared with HIV-negative women with breast cancer. We aimed to examine how this HIV differential varies by patient or breast tumour characteristics. METHODS: The African Breast Cancer-Disparities in Outcomes (ABC-DO) study is a prospective cohort of women (aged ≥18 years) with incident breast cancer recruited consecutively at diagnosis (2014-17) from hospitals in Namibia, Nigeria, South Africa, Uganda, and Zambia. Detailed clinical and epidemiological data, including self-reported or tested HIV status, were collected at baseline. Participants were actively followed up via telephone calls every 3 months. The primary outcome was all-cause mortality, assessed in all women who had at least one updated vital status after baseline interview. Using Cox regression, we examined differences in overall survival by HIV status in the cohort, and across country and patient subgroups, adjusted for age, tumour grade, and tumour stage at cancer diagnosis. FINDINGS: Between Sept 8, 2014, and Dec 31, 2017, we recruited 2154 women with primary breast cancer, 519 of whom were excluded due to their countries having small numbers of women with HIV for comparison. Among the remaining 1635 women, 313 (19%) were living with HIV, 1184 (72%) were HIV negative, and 138 (9%) had unknown HIV status. At breast cancer diagnosis, women with HIV were younger and had lower body-mass index (BMI) than their HIV-negative counterparts, but had similar tumour stage, grade, and receptor subtypes. At the end of the follow-up (Jan 1, 2019), a higher proportion of women with HIV (137 [44%] of 313) had died than had HIV-negative women (432 [37%] of 1184). Crude 3-year survival was 9% lower for women with HIV (46% [95% CI 40-53]) than for HIV-negative women (55% [52-59]; hazard ratio (HR) 1·41 [1·15-1·74]). The HIV survival differential did not differ by age, BMI, tumour subtype, or tumour grade, but was stronger in women with non-metastatic disease (3-year survival 52% HIV-positive vs 63% HIV-negative women, adjusted HR 1·65 [1·30-2·10]), whereas women with metastatic cancer had low survival, regardless of HIV status. INTERPRETATION: The larger survival deficit among women with HIV with non-metastatic breast cancer calls for a better understanding of the reasons underlying this differential (eg, biological mechanisms, health behaviours, detrimental HIV-breast cancer treatment interactions, or higher HIV background mortality) to inform strategies for reducing mortality among this patient group. FUNDING: Susan G Komen, International Agency for Research on Cancer, National Cancer Institute, and UK-Commonwealth Scholarships.
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- 2022
15. Alcohol consumption and oesophageal squamous cell cancer risk in east Africa: findings from the large multicentre ESCCAPE case-control study in Kenya, Tanzania, and Malawi
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Daniel R S Middleton, Blandina T Mmbaga, Diana Menya, Charles Dzamalala, Gissela Nyakunga-Maro, Peter Finch, Yohannie Mlombe, Joachim Schüz, Valerie McCormack, Nicolas Kigen, Margaret Oduor, Stephen Karuru Maina, Fatima Some, Caroline Kibosia, Amos Mwasamwaja, Alex Mremi, Ireen Kiwelu, Remigi Swai, Godwin Kiwelu, Sophia Mustapha, Eliawawomy Mghase, Amana Mchome, Redfan Shao, Evarista Mallya, Kajiru Kilonzo, Anstead Kamkwantira, Mercy Kamdolozi, George Liomba, Steady Chasimpha, Clement Narh, Liacine Bouaoun, Behnoush Abedi-Ardekani, Godfrey Mushi, Theresia Namwai, Mary Suwedi, Thandiwe Solomon, Rose Malamba, and Christine Carreira
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Alcohol Drinking ,Esophageal Neoplasms ,Risk Factors ,parasitic diseases ,Humans ,Articles ,Esophageal Squamous Cell Carcinoma ,General Medicine ,Africa South of the Sahara - Abstract
Summary Background The contribution of alcohol to the large burden of oesophageal squamous cell carcinoma (ESCC) in east Africa remains uncertain and difficult to assess owing to complex consumption patterns of traditional and commercial drinks. We aimed to assess whether alcohol drinking, overall and at specific intake levels, contributes to ESCC risk in east Africa. Methods We did a hospital-based case-control study in Kenya, Tanzania, and Malawi, which included comprehensive assessment of a variety of locally consumed alcohol that we used to classify drinkers as exclusively low alcohol-by-volume (ABV
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- 2022
16. Correction: Multimorbidity and overall survival among women with breast cancer: results from the South African Breast Cancer and HIV Outcomes Study
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Oluwatosin A. Ayeni, Maureen Jofe, Witness Mapanga, Wenlong Carl Chen, Daniel S. O’Neil, Boitumelo Phakathi, Sarah Nietz, Ines Buccimazza, Sharon Čačala, Laura W. Stopforth, Judith S. Jacobson, Katherine D. Crew, Alfred I. Neugut, Duvern Ramiah, Paul Ruf, Herbert Cubasch, Tobias Chirwa, Valerie McCormack, Lisa K. Micklesfeld, and Shane A. Norris
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- 2023
17. Mutational signatures in esophageal squamous cell carcinoma from eight countries with varying incidence
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S M Ashiqul Islam, Irina I. Abnizova, James McKay, Yudou He, Estelle Chanudet, Behnoush Abedi-Ardekani, Dariush Nasrollahzadeh, Michael Eden, Alisa M. Goldstein, Jon W. Teague, Blandina T. Mmbaga, Nan Hu, Karl Smith-Byrne, Sandra Perdomo, Jingwei Wang, Christine Carreira, Jean-Yves Scoazec, Rebecca C. Fitzgerald, Luis Felipe Ribeiro, Michael R. Stratton, Samad Gharavi, Sergey Senkin, Erik N Bergstrom, Hiva Saffar, Sarah Moody, Sheila Coelho Soares-Lima, Pauline E Bucciarelli, Stefano Serra, Ghislaine Scelo, Charles Dzamalala, Valerie McCormack, Reza Malekzadeh, Hossein Poustchi, Valerie Gaborieau, Lia S Campos, Joshua R. Atkins, Paul Brennan, Emily Thomas, David T. Jones, Paul Richman, Farid Azmoudeh-Ardalan, Masoud Sotoudeh, Ahmadreza Niavarani, Tatsuhiro Shibata, Calli Latimer, Stephen Fitzgerald, Ludmil B Alexandrov, Ricardo Cortez Cardoso Penha, Abdolreza Fazel, Laura Humphreys, Azhar Khandekar, Arash Nikmanesh, and Diana Menya
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Adult ,Male ,APOBEC ,China ,Esophageal Neoplasms ,Apolipoprotein B ,Iran ,Biology ,medicine.disease_cause ,Genome ,Esophageal squamous cell carcinoma ,Germline ,03 medical and health sciences ,0302 clinical medicine ,Epidemiology of cancer ,Genetics ,medicine ,Humans ,APOBEC Deaminases ,Aged ,030304 developmental biology ,Aged, 80 and over ,0303 health sciences ,Mutation ,Whole Genome Sequencing ,Aldehyde Dehydrogenase, Mitochondrial ,Incidence ,Incidence (epidemiology) ,Middle Aged ,United Kingdom ,digestive system diseases ,3. Good health ,030220 oncology & carcinogenesis ,biology.protein ,Cancer research ,Female ,Esophageal Squamous Cell Carcinoma ,Tumor Suppressor Protein p53 ,Brazil - Abstract
Esophageal squamous cell carcinoma (ESCC) shows remarkable variation in incidence that is not fully explained by known lifestyle and environmental risk factors. It has been speculated that an unknown exogenous exposure(s) could be responsible. Here we combine the fields of mutational signature analysis with cancer epidemiology to study 552 ESCC genomes from eight countries with varying incidence rates. Mutational profiles were similar across all countries studied. Associations between specific mutational signatures and ESCC risk factors were identified for tobacco, alcohol, opium and germline variants, with modest impacts on mutation burden. We find no evidence of a mutational signature indicative of an exogenous exposure capable of explaining differences in ESCC incidence. Apolipoprotein B mRNA-editing enzyme, catalytic polypeptide-like (APOBEC)-associated mutational signatures single-base substitution (SBS)2 and SBS13 were present in 88% and 91% of cases, respectively, and accounted for 25% of the mutation burden on average, indicating that APOBEC activation is a crucial step in ESCC tumor development.
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- 2021
18. Global and regional estimates of orphans attributed to maternal cancer mortality in 2020
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Florence, Guida, Rachel, Kidman, Jacques, Ferlay, Joachim, Schüz, Isabelle, Soerjomataram, Benda, Kithaka, Ophira, Ginsburg, Raymond B, Mailhot Vega, Moses, Galukande, Groesbeck, Parham, Salvatore, Vaccarella, Karen, Canfell, Andre M, Ilbawi, Benjamin O, Anderson, Freddie, Bray, Isabel, Dos-Santos-Silva, and Valerie, McCormack
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Fertility ,Adolescent ,Pregnancy ,Cause of Death ,Neoplasms ,Africa ,Humans ,Female ,Mortality ,Child ,Global Health - Abstract
Despite women being disproportionally affected by cancer deaths at young ages, there are no global estimates of the resulting maternal orphans, who experience health and education disadvantages throughout their lives. We estimated the number of children who became maternal orphans in 2020 due to their mother dying from cancer in that year, for 185 countries worldwide and by cause of cancer-related death. Female cancer deaths-by country, cancer type and age (derived from GLOBOCAN estimates)-were multiplied by each woman's estimated number of children under the age of 18 years at the time of her death (fertility data were derived from United Nations World Population Prospects for birth cohort), accounting for child mortality and parity-cancer risk associations. Globally, there were 1,047,000 such orphans. Over half of these were orphans due to maternal deaths from breast (258,000, 25%), cervix (210,000, 20%) and upper-gastrointestinal cancers (136,000, 13%), and most occurred in Asia (48%: India 15%, China 10%, rest of Asia 23%) and Africa (35%). Globally, there were 40 new maternal orphans due to cancer per 100,000 children, with a declining trend with a higher Human Development Index (range: 121 in Malawi to 15 in Malta). An estimated 7 million children were prevalent maternal orphans due to cancer in mid-2020. Accelerating the implementation of the World Health Organization's cervical and breast cancer initiatives has the potential to avert not only millions of preventable female cancer deaths but also the associated, often-overlooked, intergenerational consequences of these deaths.
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- 2022
19. Household air pollution, polycyclic aromatic hydrocarbons and esophageal cancer risk in Kenya: ESCCAPE case-control study
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James Watson, Diana Menya, Elisa Puzzolo, Iva Cukic, Edna Sang, Craig Sams, Daniel Middleton, Joachim Schüz, Valerie McCormack, and Daniel Pope
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General Earth and Planetary Sciences ,General Environmental Science - Published
- 2022
20. The association of age at menarche and adult height with mammographic density in the International Consortium of Mammographic Density
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Sarah V. Ward, Anya Burton, Rulla M. Tamimi, Ana Pereira, Maria Luisa Garmendia, Marina Pollan, Norman Boyd, Isabel dos-Santos-Silva, Gertraud Maskarinec, Beatriz Perez-Gomez, Celine Vachon, Hui Miao, Martín Lajous, Ruy López-Ridaura, Kimberly Bertrand, Ava Kwong, Giske Ursin, Eunjung Lee, Huiyan Ma, Sarah Vinnicombe, Sue Moss, Steve Allen, Rose Ndumia, Sudhir Vinayak, Soo-Hwang Teo, Shivaani Mariapun, Beata Peplonska, Agnieszka Bukowska-Damska, Chisato Nagata, John Hopper, Graham Giles, Vahit Ozmen, Mustafa Erkin Aribal, Joachim Schüz, Carla H. Van Gils, Johanna O. P. Wanders, Reza Sirous, Mehri Sirous, John Hipwell, Jisun Kim, Jong Won Lee, Caroline Dickens, Mikael Hartman, Kee-Seng Chia, Christopher Scott, Anna M. Chiarelli, Linda Linton, Anath Arzee Flugelman, Dorria Salem, Rasha Kamal, Valerie McCormack, Jennifer Stone, NIH - National Cancer Institute (NCI) (Estados Unidos), International Agency for Research on Cancer, Cancer Council Western Australia (Australia), University of Western Australia (Australia), Australia VicHealth, Cancer Council Victoria (Australia), National Health and Medical Research Council (Australia), National Breast Cancer Foundation (Australia), National Cancer Institute (Canada), Fondecyt (Chile), World Cancer Research Fund International, Larry Ellison Foundation, Isfahan University of Technology (Irán), Israel Cancer Association, Asan Medical Center (Korea), Malaysia Sime Darby LPGA Tournament, Ministry of Education University (Malasia), University of Malaya (Malasia), Consejo Nacional de Ciencia y Tecnología (México), American Institute for Cancer Research, Unión Europea. Comisión Europea, Ministry of Health (Holanda), Dutch Cancer Society (Holanda), Netherlands Organisation for Health Research and Development, National Medical Research Council (Singapur), National University Cancer Institute (Singapur), South Africa Pink Drive, Instituto de Salud Carlos III, Federación Española de Padres de Niños con Cáncer, Turkey-Roche Mustahzarlari San, Engineering and Physical Sciences Research Council (Reino Unido), Breast Cancer Campaign (Reino Unido), Cancer Research UK (Reino Unido), Da Costa Foundation, and Susan G. Komen Breast Cancer Foundation
- Subjects
Adult ,Breast Neoplasms/diagnostic imaging ,Menarche ,Height ,Mammography/methods ,Breast Neoplasms ,Breast cancer ,Cross-Sectional Studies ,Population Groups ,Pregnancy ,Risk Factors ,Humans ,Female ,Mammographic density ,Mammography ,Breast Density - Abstract
Background: Early age at menarche and tall stature are associated with increased breast cancer risk. We examined whether these associations were also positively associated with mammographic density, a strong marker of breast cancer risk. Methods: Participants were 10,681 breast-cancer-free women from 22 countries in the International Consortium of Mammographic Density, each with centrally assessed mammographic density and a common set of epidemiologic data. Study periods for the 27 studies ranged from 1987 to 2014. Multi-level linear regression models estimated changes in square-root per cent density (√PD) and dense area (√DA) associated with age at menarche and adult height in pooled analyses and population-specific meta-analyses. Models were adjusted for age at mammogram, body mass index, menopausal status, hormone therapy use, mammography view and type, mammographic density assessor, parity and height/age at menarche. Results: In pooled analyses, later age at menarche was associated with higher per cent density (β√PD = 0.023 SE = 0.008, P = 0.003) and larger dense area (β√DA = 0.032 SE = 0.010, P = 0.002). Taller women had larger dense area (β√DA = 0.069 SE = 0.028, P = 0.012) and higher per cent density (β√PD = 0.044, SE = 0.023, P = 0.054), although the observed effect on per cent density depended upon the adjustment used for body size. Similar overall effect estimates were observed in meta-analyses across population groups. Conclusions: In one of the largest international studies to date, later age at menarche was positively associated with mammographic density. This is in contrast to its association with breast cancer risk, providing little evidence of mediation. Increased height was also positively associated with mammographic density, particularly dense area. These results suggest a complex relationship between growth and development, mammographic density and breast cancer risk. Future studies should evaluate the potential mediation of the breast cancer effects of taller stature through absolute breast density. This work was supported by the US National Cancer Institute at the National Institutes of Health [R03CA167771]; the International Agency for Research on Cancer; the University of Western Australia [Research Collaboration Award] and the Cancer Council Western Australia [Capacity Building and Collaboration Grant]. Original studies were supported, according to country by: Australia VicHealth; Cancer Council Victoria; Australian National Health and Medical Research Council [209057, 251,553 and 504711]; Australian National Breast Cancer Foundation [to JSt]; Canada the National Cancer Institute of Canada [to NFB]; Chile Fondecyt [11100238 to MLG, 1120326, 1130277, 3130532]; World Cancer Research Fund [2010/245]; Ellison Medical Foundation Grant [to AP]; Iran Isfahan University of Medical Sciences; Israel The Israel Cancer Association; Republic of Korea Asan Medical Center [2010-0811]; Malaysia Sime Darby LPGA Tournament; Ministry of Education University Malaya [High Impact Research Grant UM.C/HIR/MOHE/06]; University Malaya [Research Grant UMRG RP046B-15HTM]; Mexico National Council of Science and Technology (Mexico); the American Institute for Cancer Research [10A035]; Netherlands EPIC-NL-Europe against Cancer Programme of the European Commission (SANCO); Dutch Ministry of Health; Dutch Cancer Society; ZonMW the Netherlands Organisation for Health Research and Development; World Cancer Research Fund (WCRF); Poland Polish-Norwegian Research Programme [PNRF-243-AI-1/07]; Singapore National Medical Research Council [Clinician Scientist Award]; National University Cancer Institute Singapore (NCIS) Centre grant programme from National Medical Research Council; South Africa Pink Drive; Spain Spain’s Health Research Fund (Fondo de Investigacion Santiaria) [PI060386 and PS09/0790]; Spanish Federation of Breast Cancer Patients (FECMA) [EPY1169-10]; Turkey-Roche Mustahzarlari San. A.S., Istanbul, Turkey; UK UK Engineering and Physical Sciences Research Council [EP/K020439/1 to JHi]; Breast Cancer Campaign [2007MayPR23], Cancer Research UK [G186/11 and C405/A14565]; Da Costa Foundation UK; USA National Cancer Institute [R01CA85265, R37 CA54281, R01 CA97396, P50 CA116201, R01 CA177150 and R01 CA140286]; Cancer Center Support Grant [CA15083; CA131332, CA124865, UM1 CA186107 and UM1 CA176726]; the Susan G. Komen Foundation. Sí
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- 2022
21. Esophageal Cancer in Tanzania: A Welcome Stimulus in Primary Prevention Research
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Bongani Kaimila, Blandina T. Mmbaga, Joachim Schüz, and Valerie McCormack
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0301 basic medicine ,Stimulus (economics) ,Esophageal Neoplasms ,Epidemiology ,Tanzania ,03 medical and health sciences ,0302 clinical medicine ,Risk Factors ,Environmental health ,Global health ,medicine ,Humans ,Life Style ,Exposure assessment ,biology ,business.industry ,Clinical study design ,Cancer ,Esophageal cancer ,medicine.disease ,biology.organism_classification ,Causality ,Primary Prevention ,030104 developmental biology ,Oncology ,Case-Control Studies ,030220 oncology & carcinogenesis ,business - Abstract
In this issue, Mmbaga and colleagues present results of a case–control study to investigate environmental and lifestyle risk factors for esophageal cancer in Tanzania, East Africa. The results contribute to the early stage of a growing evidence base aimed to inform primary prevention of a major poor prognosis cancer in East Africa. In this commentary, we first discuss considerations needed to evaluate causality of associations, a feature needed for primary prevention. There is a need for further studies across the African esophageal cancer corridor, for more refined exposure assessment and a careful consideration of potential epidemiologic biases within study designs for real-life situations in the setting. This study also forms a prime example of the broader research needs for cancer in low- and middle-income countries and in Sub-Saharan Africa, a setting with distinct and underresearched cancers and exposure patterns. While this etiologic research is challenging, it is an essential component of the ground-shot approach to global health research needed to inform primary prevention. See related article by Mmbaga et al., p. 305
- Published
- 2021
22. Preexisting morbidity profile of women newly diagnosed with breast cancer in sub‐Saharan Africa: African Breast Cancer—Disparities in Outcomes study
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Milena Foerster, Valerie McCormack, Herbert Cubasch, Isabel dos Santos Silva, Joachim Schüz, Annelle Zietsman, Oluwatosin Ayeni, Angelica Anele, Moses Galukande, Groesbeck P. Parham, Shane A. Norris, Charles Adisa, Benjamin O. Anderson, and Maureen Joffe
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Cancer Research ,Chronic condition ,medicine.medical_specialty ,Tuberculosis ,multimorbidity ,Breast Neoplasms ,chronic condition ,Article ,03 medical and health sciences ,breast cancer ,0302 clinical medicine ,Breast cancer ,Diabetes mellitus ,Internal medicine ,stage at diagnosis and sub-Saharan Africa ,Outcome Assessment, Health Care ,medicine ,Humans ,Healthcare Disparities ,Africa South of the Sahara ,business.industry ,Cancer ,Odds ratio ,medicine.disease ,Survival Analysis ,Obesity ,Oncology ,030220 oncology & carcinogenesis ,Cohort ,Female ,business - Abstract
The presence of preexisting morbidities poses a challenge to cancer patient care. There is little information on the profile and prevalence of multi-morbidities in breast cancer patients across middle income countries (MIC) to lower income countries (LIC) in sub-Saharan Africa (SSA). The African Breast Cancer–Disparities in Outcomes (ABC-DO) breast cancer cohort spans upper MICs South Africa and Namibia, lower MICs Zambia and Nigeria and LIC Uganda. At cancer diagnosis, seven morbidities were assessed: obesity, hypertension, diabetes, asthma/chronic obstructive pulmonary disease, heart disease, tuberculosis and HIV. Logistic regression models were used to assess determinants of morbidities and the influence of morbidities on advanced stage (stage III/IV) breast cancer diagnosis. Among 2189 women, morbidity prevalence was the highest for obesity (35%, country-specific range 15-57%), hypertension (32%, 15-51%) and HIV (16%, 2-26%) then for diabetes (7%, 4%-10%), asthma (4%, 2%-10%), tuberculosis (4%, 0%-8%) and heart disease (3%, 1%-7%). Obesity and hypertension were more common in upper MICs and in higher socioeconomic groups. Overall, 27% of women had at least two preexisting morbidities. Older women were more likely to have obesity (odds ratio: 1.09 per 10 years, 95% CI 1.01-1.18), hypertension (1.98, 1.81-2.17), diabetes (1.51, 1.32-1.74) and heart disease (1.69, 1.37-2.09) and were less likely to be HIV positive (0.64, 0.58-0.71). Multi-morbidity was not associated with stage at diagnosis, with the exception of earlier stage in obese and hypertensive women. Breast cancer patients in higher income countries and higher social groups in SSA face the additional burden of preexisting non-communicable diseases, particularly obesity and hypertension, exacerbated by HIV in Southern/Eastern Africa.
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- 2020
23. Multimorbidity and overall survival among women with breast cancer: Results from the South African breast cancer and HIV outcomes study
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Oluwatosin A. Ayeni, Maureen Joffe, Witness Mapanga, Wenlong Carl Chen, Daniel S. O’Neil, Boitumelo Phakathi, Sarah Nietz, Ines Buccimazza, Sharon Čačala, Laura W. Stopforth, Judith S. Jacobson, Katherine D. Crew, Alfred I. Neugut, Duvern Ramiah, Paul Ruff, Herbert Cubasch, Tobias Chirwa, Valerie McCormack, Lisa K. Micklesfield, and Shane A. Norris
- Abstract
Background Breast cancer survival in South Africa is low, but when diagnosed with breast cancer, many women in South Africa also have other chronic conditions. We investigated the impact of multimorbidity (≥ 2 other chronic conditions) on overall survival among women with breast cancer in South Africa. Methods Between 1 July 2015 and 31 December 2019, we enrolled women newly diagnosed with breast cancer at six public hospitals participating in the South African Breast Cancer and HIV Outcomes (SABCHO) Study. We examined seven chronic conditions (obesity, hypertension, diabetes, HIV, cerebrovascular diseases (CVD), asthma/chronic obstructive pulmonary disease, and tuberculosis), and we compared socio-demographic, clinical, and treatment factors between patients with and without each condition, and with and without multimorbidity. We investigated the association of multimorbidity with overall survival using multivariable Cox proportional hazard models. Results Of 3,261 women included in the analysis, 45% had multimorbidity; obesity (53%), hypertension (41%), HIV (22%), and diabetes (13%) were the most common individual conditions. Women with multimorbidity had poorer overall survival at 3 years than women without multimorbidity in both the full cohort (60.8% vs. 64.3%, p = 0.036) and stage groups: stages I–II, 80.7% vs. 86.3% (p = 0.005), and stage III, 53.0% vs. 59.4% (p = 0.024). In an adjusted model, women with diabetes (hazard ratio (HR) = 1.20, 95% confidence interval (CI) = 1.03–1.41), CVD (HR = 1.43, 95% CI = 1.17–1.76), HIV (HR = 1.21, 95% CI = 1.06–1.38), obesity + HIV (HR = 1.24 95% CI = 1.04–1.48), and multimorbidity (HR = 1.26, 95% CI = 1.13–1.40) had poorer overall survival than women without these conditions. Conclusions Irrespective of the stage, multimorbidity at breast cancer diagnosis was an important prognostic factor for survival in our SABCHO cohort. The high prevalence of multimorbidity in our cohort calls for more comprehensive care to improve outcomes for South African women with breast cancer.
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- 2022
24. An international report on bacterial communities in esophageal squamous cell carcinoma
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Jason Nomburg, Susan Bullman, Dariush Nasrollahzadeh, Eric A. Collisson, Behnoush Abedi‐Ardekani, Larry O. Akoko, Joshua R. Atkins, Geoffrey C. Buckle, Satish Gopal, Nan Hu, Bongani Kaimila, Masoud Khoshnia, Reza Malekzadeh, Diana Menya, Blandina T. Mmbaga, Sarah Moody, Gift Mulima, Beatrice P. Mushi, Julius Mwaiselage, Ally Mwanga, Yulia Newton, Dianna L. Ng, Amie Radenbaugh, Deogratias S. Rwakatema, Msiba Selekwa, Joachim Schüz, Philip R. Taylor, Charles Vaske, Alisa Goldstein, Michael R. Stratton, Valerie McCormack, Paul Brennan, James A. DeCaprio, Matthew Meyerson, Elia J. Mmbaga, and Katherine Van Loon
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Cancer Research ,Oncology ,Bacteria ,Esophageal Neoplasms ,Microbiota ,Humans ,Esophageal Squamous Cell Carcinoma ,Kenya - Abstract
The incidence of esophageal squamous cell carcinoma (ESCC) is disproportionately high in the eastern corridor of Africa and parts of Asia. Emerging research has identified a potential association between poor oral health and ESCC. One possible link between poor oral health and ESCC involves the alteration of the microbiome. We performed an integrated analysis of four independent sequencing efforts of ESCC tumors from patients from high- and low-incidence regions of the world. Using whole genome sequencing (WGS) and RNA sequencing (RNAseq) of ESCC tumors from 61 patients in Tanzania, we identified a community of bacteria, including members of the genera Fusobacterium, Selenomonas, Prevotella, Streptococcus, Porphyromonas, Veillonella and Campylobacter, present at high abundance in ESCC tumors. We then characterized the microbiome of 238 ESCC tumor specimens collected in two additional independent sequencing efforts consisting of patients from other high-ESCC incidence regions (Tanzania, Malawi, Kenya, Iran, China). This analysis revealed similar ESCC-associated bacterial communities in these cancers. Because these genera are traditionally considered members of the oral microbiota, we next explored whether there was a relationship between the synchronous saliva and tumor microbiomes of ESCC patients in Tanzania. Comparative analyses revealed that paired saliva and tumor microbiomes were significantly similar with a specific enrichment of Fusobacterium and Prevotella in the tumor microbiome. Together, these data indicate that cancer-associated oral bacteria are associated with ESCC tumors at the time of diagnosis and support a model in which oral bacteria are present in high abundance in both saliva and tumors of some ESCC patients.
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- 2022
25. Impact of HIV infection on survival among women with stage I-III breast cancer: Results from the South African breast cancer and HIV outcomes study
- Author
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Oluwatosin A. Ayeni, Daniel S. O'Neil, Yoanna S. Pumpalova, Wenlong Carl Chen, Sarah Nietz, Boitumelo Phakathi, Ines Buccimazza, Sharon Čačala, Laura W. Stopforth, Hayley A. Farrow, Witness Mapanga, Maureen Joffe, Tobias Chirwa, Valerie McCormack, Judith S. Jacobson, Katherine D. Crew, Alfred I. Neugut, Paul Ruff, and Herbert Cubasch
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Cancer Research ,South Africa ,Oncology ,Humans ,Breast Neoplasms ,Female ,HIV Infections ,Middle Aged ,Viral Load ,Proportional Hazards Models - Abstract
In some countries of sub-Saharan Africa, the prevalence of HIV exceeds 20%; in South Africa, 20.4% of people are living with HIV. We examined the impact of HIV infection on the overall survival (OS) of women with nonmetastatic breast cancer (BC) enrolled in the South African Breast Cancer and HIV Outcomes (SABCHO) study. We recruited women with newly diagnosed BC at six public hospitals from 1 July 2015 to 30 June 2019. Among women with stages I-III BC, we compared those with and without HIV infection on sociodemographic, clinical, and treatment factors. We analyzed the impact of HIV on OS using multivariable Cox proportional hazard models. Of 2367 women with stages I-III BC, 499 (21.1%) had HIV and 1868 (78.9%) did not. With a median follow-up of 29 months, 2-year OS was poorer among women living with HIV (WLWH) than among HIV-uninfected women (72.4% vs 80.1%, P .001; adjusted hazard ratio (aHR) 1.49, 95% confidence interval (CI) = 1.22-1.83). This finding was consistent across age groups ≥45 years and45 years, stage I-II BC and stage III BC, and ER/PR status (all P .03). Both WLWH with50 viral load copies/mL and WLWH with ≥50 viral load copies/mL had poorer survival than HIV-uninfected BC patients [aHR: 1.35 (1.09-1.66) and 1.54 (1.20-2.00), respectively], as did WLWH who had ≥200 CD4+ cells/mL at diagnosis [aHR: 1.39 (1.15-1.67)]. Because receipt of antiretroviral therapy has become widespread, WLWH is surviving long enough to develop BC; more research is needed on the causes of their poor survival.
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- 2022
26. Dissecting the journey to breast cancer diagnosis in sub‐Saharan Africa: Findings from the multicountry <scp>ABC‐DO</scp> cohort study
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Isabel dos-Santos-Silva, Milena Foerster, Charles Adisa, Annelle Zietsman, Valerie McCormack, Fiona McKenzie, Groesbeck P. Parham, Leeya F. Pinder, Joachim Schüz, Angelica Anele, and Moses Galukande
- Subjects
Cancer Research ,Pediatrics ,medicine.medical_specialty ,Delayed Diagnosis ,Referral ,Psychological intervention ,Breast Neoplasms ,Disease ,Health Services Accessibility ,Cohort Studies ,03 medical and health sciences ,breast cancer ,0302 clinical medicine ,Breast cancer ,cancer diagnosis ,medicine ,Humans ,Africa South of the Sahara ,Neoplasm Staging ,business.industry ,Breast cancer awareness ,Cancer ,Middle Aged ,medicine.disease ,Socioeconomic Factors ,Oncology ,030220 oncology & carcinogenesis ,Africa ,Cohort ,Regression Analysis ,Female ,business ,Cancer Epidemiology ,early diagnosis ,Cohort study - Abstract
Most breast cancer patients in sub‐Saharan Africa are diagnosed at advanced stages after prolonged symptomatic periods. In the multicountry African Breast Cancer‐Disparities in Outcomes cohort, we dissected the diagnostic journey to inform downstaging interventions. At hospital presentation for breast cancer, women recalled their diagnostic journey, including dates of first noticing symptoms and health‐care provider (HCP) visits. Negative binomial regression models were used to identify correlates of the length of the diagnostic journey. Among 1429 women, the median (inter‐quartile range) length (months) of the diagnostic journey ranged from 11.3 (5.7‐21.2) in Ugandan, 8.2 (3.4‐16.4) in Zambian, 6.5 (2.4‐15.7) in Namibian‐black to 5.6 (2.3‐13.1) in Nigerian and 2.4 (0.6‐5.5) in Namibian‐non‐black women. Time from first HCP contact to diagnosis represented, on average, 58% to 79% of the diagnostic journey in each setting except Nigeria where most women presented directly to the diagnostic hospital with advanced disease. The median number of HCPs visited was 1 to 4 per woman, but time intervals between visits were long. Women who attributed their initial symptoms to cancer had a 4.1 months (absolute) reduced diagnostic journey than those who did not, while less‐educated (none/primary) women had a 3.6 months longer journey than more educated women. In most settings the long journey to breast cancer diagnosis was not primarily due to late first presentation but to prolonged delays after first presentation to diagnosis. Promotion of breast cancer awareness and implementation of accelerated referral pathways for women with suspicious symptoms are vital to downstaging the disease in the region., What's new? In sub‐Saharan Africa, most women with breast cancer are diagnosed long after symptoms first arise. Here, the authors studied the diagnostic journey for breast cancer among the African Breast Cancer‐Disparities in Outcome cohort. This is the largest study to quantify the length of the diagnostic journey across various settings in sub‐Saharan Africa. Time to final diagnosis decreased substantially when a woman recognized her symptoms as cancer. Most delays, they found, were due to extended time between first examination and final diagnosis. Promotion of breast cancer awareness among both women and healthcare providers could help reduce these delays.
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- 2020
27. Global burden and trends in premenopausal and postmenopausal breast cancer: a population-based study
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Noah Escandor, Hyuna Sung, Emily Heer, Valerie McCormack, Miranda M Fidler-Benaoudia, and Andrew Harper
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medicine.medical_specialty ,030231 tropical medicine ,Population ,Breast Neoplasms ,Global Health ,03 medical and health sciences ,0302 clinical medicine ,Breast cancer ,Incidence trends ,medicine ,Humans ,In patient ,030212 general & internal medicine ,skin and connective tissue diseases ,education ,education.field_of_study ,Postmenopausal women ,business.industry ,Obstetrics ,lcsh:Public aspects of medicine ,Incidence ,Incidence (epidemiology) ,lcsh:RA1-1270 ,General Medicine ,Middle Aged ,medicine.disease ,Postmenopause ,Population based study ,Premenopause ,Premenopausal breast cancer ,Female ,business - Abstract
Summary Background Breast cancer has distinct causes, prognoses, and outcomes and effects in patients at premenopausal and postmenopausal ages. We sought to assess the global burden and trends in breast cancer by menopausal status. Methods We did a population-based analysis of global breast cancer incidence and mortality among premenopausal and postmenopausal women. Menopausal status was defined using age as a proxy, whereby breast cancer cases or deaths at age 50 years or older were regarded as postmenopausal. Age-standardised breast cancer incidence and mortality in 2018 were calculated using GLOBOCAN data. Incidence trends for 1998–2012 were assessed in 44 populations from 41 countries using the Cancer in Five Continents plus database, by calculating the annual average percent change. Findings Approximately 645 000 premenopausal and 1·4 million postmenopausal breast cancer cases were diagnosed worldwide in 2018, with more than 130 000 and 490 000 deaths occurring in each menopausal group, respectively. Proportionally, countries with a low UNDP human development index (HDI) faced a greater burden of premenopausal breast cancer for both new cases and deaths compared with higher income countries. Countries with a very high HDI had the highest premenopausal and postmenopausal breast cancer incidence (30·6 and 253·6 cases per 100 000, respectively), whereas countries with low and medium HDI had the highest premenopausal and postmenopausal mortality, respectively (8·5 and 53·3 deaths per 100 000, respectively). When examining breast cancer trends, we noted significantly increasing age-standardised incidence rates (ASIRs) for premenopausal breast cancer in 20 of 44 populations and significantly increasing ASIRs for postmenopausal breast cancer in 24 of 44 populations. The growth exclusively at premenopausal ages largely occurred in high-income countries, whereas the increasing postmenopausal breast cancer burden was most notable in countries under transition. Interpretation We provide evidence of a rising burden of both premenopausal and postmenopausal breast cancer worldwide. Although early diagnosis and access to treatment remain crucial in low-income and middle-income countries, primary prevention efforts seeking to decrease exposure to known breast cancer risk factors are warranted in all world regions to curb the future breast cancer burden. Funding None.
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- 2020
28. Few Losses to Follow-up in a Sub-Saharan African Cancer Cohort via Active Mobile Health Follow-up
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Charles Adisa, Christopher Sule Oyamienlen, Benjamin O. Anderson, Annelle Zietsman, Agnes Kaggwa, Emily Walubita, Groesbeck P. Parham, Isabel dos Santos Silva, Leeya F. Pinder, Kingsley Chukwunyere Iwuoha, Evelyn Bakengesa, Joachim Schüz, Allen Naamala, Esther Ezeigbo, Teopista Nakazibwe, Fiona McKenzie, Johanna Pontac, Angelica Anele, Moses Galukande, Anne Nteziryayo, Valerie McCormack, and Milena Foerster
- Subjects
Epidemiology ,business.industry ,Cancer ,medicine.disease ,law.invention ,03 medical and health sciences ,0302 clinical medicine ,Breast cancer ,Randomized controlled trial ,Interquartile range ,law ,030220 oncology & carcinogenesis ,Cohort ,medicine ,Cumulative incidence ,030212 general & internal medicine ,Prospective cohort study ,business ,Cohort study ,Demography - Abstract
Accurate survival estimates are needed for guiding cancer control efforts in sub-Saharan Africa, but previous studies have been hampered by unknown biases due to excessive loss to follow-up (LTFU). In the African Breast Cancer—Disparities in Outcomes Study, a prospective breast cancer cohort study, we implemented active mobile health follow-up, telephoning each woman or her next-of-kin (NOK) trimonthly on her mobile phone to update information on her vital status. Dates of every contact with women/NOK were analyzed from diagnosis in 2014–2017 to the earliest of September 1, 2018, death, or 3 years postdiagnosis. The cumulative incidence of being LTFU was calculated considering deaths as competing events. In all, 1,490 women were followed for a median of 24.2 (interquartile range (IQR), 14.2–34.5) months, corresponding to 8,529 successful contacts (77% of total contacts) with the women/NOK. Median time between successful contacts was 3.0 (IQR, 3.0–3.7) months. In all, 71 women (5.3%) were LTFU at 3 years: 0.8% in Nigeria, 2.2% in Namibia, and 5.6% in Uganda. Because of temporary discontinuity of active follow-up, 20.3% of women were LTFU after 2 years in Zambia. The median time to study notification of a death was 9.1 (IQR, 3.9–14.0) weeks. Although the present study was not a randomized controlled trial, in this cancer cohort with active mobile health follow-up, LTFU was much lower than in previous studies and enabled estimation of up-to-date and reliable cancer survival.
- Published
- 2020
29. Current Status and Future Prospects for Esophageal Cancer
- Author
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Mahdi Sheikh, Gholamreza Roshandel, Valerie McCormack, and Reza Malekzadeh
- Subjects
Cancer Research ,Oncology - Abstract
Esophageal cancer (EC) is the ninth most common cancer and the sixth leading cause of cancer deaths worldwide. Esophageal squamous cell carcinoma (ESCC) and esophageal adenocarcinoma (EAC) are the two main histological subtypes with distinct epidemiological and clinical features. While the global incidence of ESCC is declining, the incidence of EAC is increasing in many countries. Decades of epidemiologic research have identified distinct environmental exposures for ESCC and EAC subtypes. Recent advances in understanding the genomic aspects of EC have advanced our understanding of EC causes and led to using specific genomic alterations in EC tumors as biomarkers for early diagnosis, treatment, and prognosis of this cancer. Nevertheless, the prognosis of EC is still poor, with a five-year survival rate of less than 20%. Currently, there are significant challenges for early detection and secondary prevention for both ESCC and EAC subtypes, but Cytosponge™ is shifting this position for EAC. Primary prevention remains the preferred strategy for reducing the global burden of EC. In this review, we will summarize recent advances, current status, and future prospects of the studies related to epidemiology, time trends, environmental risk factors, prevention, early diagnosis, and treatment for both EC subtypes.
- Published
- 2023
30. Esophageal Thermal Exposure to Hot Beverages: A Comparison of Metrics to Discriminate Distinct Consumption Habits
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Wenqiang Wei, Liacine Bouaoun, Guohui Song, Shuanghua Xie, Daniel R. S. Middleton, Graham Byrnes, Joachim Schüz, and Valerie McCormack
- Subjects
Adult ,Male ,0301 basic medicine ,China ,Hot Temperature ,Future studies ,Esophageal Neoplasms ,Epidemiology ,Drinking Behavior ,Mean difference ,Beverages ,Young Adult ,03 medical and health sciences ,0302 clinical medicine ,Humans ,Food science ,Mean radiant temperature ,Aged ,Exposure assessment ,Mathematics ,Beverage consumption ,Incidence ,Middle Aged ,Prognosis ,Confidence interval ,030104 developmental biology ,Drinking habits ,Oncology ,Human exposure ,030220 oncology & carcinogenesis ,Female ,Esophageal Squamous Cell Carcinoma ,Follow-Up Studies - Abstract
Background: Hot beverage consumption is a probable risk factor for esophageal squamous cell carcinoma (ESCC). No standardized exposure assessment protocol exists. Methods: To compare how alternative metrics discriminate distinct drinking habits, we measured sip temperatures and sizes in an international group of hot beverage drinkers in France (n = 20) and hot porridge consumers (n = 52) in a high ESCC incidence region of China. Building on the knowledge that sip size and temperature affect intraesophageal liquid temperature (IELT), IELTs were predicted by modeling existing data, and compared with first sip temperature and, across all sips, mean temperature and sip-weighted mean temperature. Results: Two contrasting exposure characteristics were observed. Compared with the international group, Chinese porridge consumers took larger first sips [mean difference +17 g; 95% confidence interval (CI), 13.3–20.7] of hotter (+9.5°C; 95% CI, 6.2–12.7) liquid, and their mean sip size did not vary greatly across sips, but the former groups increased in size as temperature decreased. This resulted in higher predicted IELTs (mean 61°C vs. 42.4°C) and sip-weighted temperatures (76.9°C vs. 56°C) in Chinese porridge consumers, and compared with first sip and mean temperature, these two metrics separated the groups to a greater extent. Conclusions: Distinguishing thermal exposure characteristics between these groups was greatly enhanced by measuring sip sizes. Temperature at first sip alone is suboptimal for assessing human exposure to hot foods and beverages, and future studies should include sip size measurements in exposure assessment protocols. Impact: This study provides a logistically feasible framework for assessing human exposure to hot beverages.
- Published
- 2019
31. A very-hot food and beverage thermal exposure index and esophageal cancer risk in Malawi and Tanzania: findings from the ESCCAPE case-control studies
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Gwinyai, Masukume, Blandina T, Mmbaga, Charles P, Dzamalala, Yohannie B, Mlombe, Peter, Finch, Gissela, Nyakunga-Maro, Alex, Mremi, Daniel R S, Middleton, Clement T, Narh, Steady J D, Chasimpha, Behnoush, Abedi-Ardekani, Diana, Menya, Joachim, Schüz, and Valerie, McCormack
- Subjects
Beverages ,Malawi ,Hot Temperature ,Logistic Models ,Esophageal Neoplasms ,Risk Factors ,Case-Control Studies ,Humans ,Esophageal Squamous Cell Carcinoma ,Tanzania - Abstract
Consumption of very-hot beverages/food is a probable carcinogen. In East Africa, we investigated esophageal squamous cell carcinoma (ESCC) risk in relation to four thermal exposure metrics separately and in a combined score.From the ESCCAPE case-control studies in Blantyre, Malawi (2017-20) and Kilimanjaro, Tanzania (2015-19), we used logistic regression models adjusted for country, age, sex, alcohol and tobacco, to estimate odds ratios (ORs) and 95% confidence intervals (CIs) for self-reported thermal exposures whilst consuming tea, coffee and/or porridge.The study included 849 cases and 906 controls. All metrics were positively associated with ESCC: temperature of drink/food (OR 1.92 (95% CI: 1.50, 2.46) for 'very hot' vs 'hot'), waiting time before drinking/eating (1.76 (1.37, 2.26) for2 vs 2-5 minutes), consumption speed (2.23 (1.78, 2.79) for 'normal' vs 'slow') and mouth burning (1.90 (1.19, 3.01) for ≥6 burns per month vs none). Amongst consumers, the composite score ranged from 1 to 12, and ESCC risk increased with higher scores, reaching an OR of 4.6 (2.1, 10.0) for scores of ≥9 vs 3.Thermal exposure metrics were strongly associated with ESCC risk. Avoidance of very-hot food/beverage consumption may contribute to the prevention of ESCC in East Africa.
- Published
- 2021
32. An international report on bacterial communities in esophageal squamous cell carcinoma
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Yulia Newton, Dariush Nasrollahzadeh, Bongani Kaimila, Deogratias Stanslaus Rwakatema, Susan Bullman, Nan Hu, Joachim Schüz, Sarah Moody, Julius Mwaiselage, Elia John Mmbaga, Behnoush Abedi-Ardekani, Joshua R. Atkins, Ally Mwanga, Gift Mulima, Blandina T. Mmbaga, James A. DeCaprio, Katherine Van Loon, Satish Gopal, Masoud Khoshnia, Paul Brennan, Alisa M. Goldstein, Amie Radenbaugh, Valerie McCormack, Reza Malekzadeh, Jason Nomburg, Matthew Meyerson, Dianna Ng, Geoffrey Buckle, Larry Akoko, Philip R. Taylor, Eric A. Collisson, Beatrice Mushi, Michael R. Stratton, Msiba Selekwa, Charles J. Vaske, and Diana Menya
- Subjects
Whole genome sequencing ,Oncology ,medicine.medical_specialty ,Saliva ,biology ,Campylobacter ,Veillonella ,biology.organism_classification ,medicine.disease_cause ,digestive system diseases ,stomatognathic diseases ,Fusobacterium ,Internal medicine ,medicine ,Prevotella ,Oral Microbiome ,Microbiome ,neoplasms - Abstract
The incidence of esophageal squamous cell carcinoma (ESCC) is disproportionately high in the eastern corridor of Africa and parts of Asia. Emerging research has identified a potential association between poor oral health and ESCC. One proposed biological pathway linking poor oral health and ESCC involves the alteration of the microbiome. Thus, we performed an integrated analysis of four independent sequencing efforts of ESCC tumors from patients from high- and low-incidence regions of the world. Using whole genome sequencing (WGS) and RNA sequencing (RNAseq) of ESCC tumors and WGS of synchronous collections of saliva specimens from 61 patients in Tanzania, we identified a community of bacteria, including members of the genera Fusobacterium, Selenomonas, Prevotella, Streptococcus, Porphyromonas, Veillonella, and Campylobacter, present at high abundance in ESCC tumors. We then characterized the microbiome of 238 ESCC tumor specimens collected in two additional independent sequencing efforts consisting of patients from other high-ESCC incidence regions (Tanzania, Malawi, Kenya, Iran, China). This analysis revealed a similar tumor enrichment of the ESCC-associated bacterial community in these cancers. Because these genera are traditionally considered members of the oral microbiota, we explored if there is a relationship between the synchronous saliva and tumor microbiomes of ESCC patients in Tanzania. Comparative analyses revealed that paired saliva and tumor microbiomes are significantly similar with a specific enrichment of Fusobacterium and Prevotella in the tumor microbiome. Together, these data indicate that cancer-associated oral bacteria are associated with ESCC tumors at the time of diagnosis and support a model in which oral bacteria are present in high abundance in both saliva and tumors of ESCC patients. Longitudinal studies of the pre-diagnostic oral microbiome are needed to investigate whether these cross-sectional similarities reflect temporal associations.
- Published
- 2021
33. Human urinary biomonitoring in Western Kenya for micronutrients and potentially harmful elements
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DanielR.S. Middleton, Elliott M. Hamilton, Diana Menya, Valerie McCormack, Olivier S. Humphrey, Michael J. Watts, Odipo Osano, and Andrew L. Marriott
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Adult ,Creatinine ,education.field_of_study ,Urinary system ,Population ,Public Health, Environmental and Occupational Health ,Urine ,Micronutrient ,Kenya ,Confidence interval ,Trace Elements ,chemistry.chemical_compound ,Animal science ,chemistry ,Reference values ,Biomonitoring ,Humans ,Micronutrients ,education ,Biological Monitoring - Abstract
Spot urinary elemental concentrations are presented for 357 adults from Western Kenya collected between 2016 and 2019 as part of a wider environmental geochemical survey. The aim of this study was to establish population level urinary elemental concentrations in Western Kenya for micronutrients and potentially harmful elements for inference of health status against established thresholds. For elements where thresholds inferring health status were not established in the literature using urine as a non-invasive matrix, this study generated reference values with a 95% confidence interval (RV95s) to contextualise urinary elemental data for this population group. Data are presented with outliers removed based upon creatinine measurements leaving 322 individuals, for sub-categories (e.g. age, gender) and by county public health administrative area. For Western Kenya, reference values with a 95% confidence interval (RV95s) were calculated as follows (μg/L): 717 (I), 89 (Se), 1753 (Zn), 336 (Mo), 24 (Cu), 15.6 (Ni), 22.1 (As), 0.34 (Cd), 0.47 (Sn), 0.46 (Sb), 7.0 (Cs), 13.4 (Ba and 1.9 (Pb). Urinary concentrations at the 25th/75th percentiles were as follows (μg/L): 149/368 (I), 15/42 (Se), 281/845 (Zn), 30/128 (Mo), 6/13 (Cu), 1.7/6.1 (Ni), 2.0/8.2 (As). 0.1/0.3 (Cd), 0.05/0.22 (Sn), 0.04/0.18 (Sb), 1.2/3.6 (Cs), 0.8/4.0 (Ba) and 0.2/0.9 (Pb). Urinary concentrations at a population level inferred excess intake of micronutrients I, Se, Zn and Mo in 38, 6, 57 and 14% of individuals, respectively, versus a bioequivalent (BE) upper threshold limit, whilst rates of deficiency were relatively low at 15, 15, 9 and 18%, respectively. Each of the administrative counties showed a broadly similar range of urinary elemental concentrations, with some exceptions for counties bordering Lake Victoria where food consumption habits may differ significantly to other counties e.g. I, Se, Zn. Corrections for urinary dilution using creatinine, specific gravity and osmolality provided a general reduction in RV95s for I, Mo, Se, As and Sn compared to uncorrected data, with consistency between the three correction methods.
- Published
- 2021
34. Self-reported arm and shoulder problems in breast cancer survivors in Sub-Saharan Africa: the African Breast Cancer-Disparities in Outcomes cohort study
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Pauline Boucheron, Valerie McCormack, Therese M.-L. Andersson, Milena Foerster, Annelle Zietsman, Joachim Schüz, Isabel dos Santos Silva, Benjamin O. Anderson, Angelica Anele, Leeya F. Pinder, Groesbeck P. Parham, and Moses Galukande
- Subjects
Adult ,medicine.medical_specialty ,Shoulder ,Arm and shoulder problems ,Shoulder pain ,Sentinel lymph node ,Breast Neoplasms ,Lymphodema ,Cohort Studies ,Breast cancer ,Quality of life ,Cancer Survivors ,Risk Factors ,Internal medicine ,Outcome Assessment, Health Care ,Medicine ,Humans ,Cumulative incidence ,Lymphedema ,RC254-282 ,Africa South of the Sahara ,Aged ,Proportional Hazards Models ,Low- and middle-income countries ,Sub-Saharan Africa ,business.industry ,Proportional hazards model ,Incidence ,Hazard ratio ,Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,Middle Aged ,medicine.disease ,Arm swelling ,Lymphoedema ,Arm stiffness ,Arm ,Female ,Self Report ,business ,Cohort study ,Research Article - Abstract
Background Arm and shoulder problems (ASP), including lymphedema, were common among women with breast cancer in high-income countries before sentinel lymph node biopsy became the standard of care. Although ASP impair quality of life, as they affect daily life activities, their frequency and determinants in Sub-Saharan Africa remain unclear. Methods All women newly diagnosed with breast cancer at the Namibian, Ugandan, Nigerian, and Zambian sites of the African Breast Cancer-Disparities in Outcomes (ABC-DO) cohort study were included. At each 3-month follow-up interview, women answered the EORTC-QLQ-Br23 questionnaire, including three ASP items: shoulder/arm pain, arm stiffness, and arm/hand swelling. We estimated the cumulative incidence of first self-reported ASP, overall and stratified by study and treatment status, with deaths treated as competing events. To identify determinants of ASP, we estimated cause-specific hazard ratios using Cox models stratified by study site. Results Among 1476 women, up to 4 years after diagnosis, 43% (95% CI 40–46), 36% (33–38) and 23% (20–25), respectively, self-reported having experienced arm/shoulder pain, stiffness and arm/hand swelling at least once. Although risks of self-reported ASP differed between sites, a more advanced breast cancer stage at diagnosis, having a lower socioeconomic position and receiving treatment increased the risk of reporting an ASP. Conclusion ASP are very common in breast cancer survivors in Sub-Saharan Africa. They are influenced by different factors than those observed in high-income countries. There is a need to raise awareness and improve management of ASP within the African setting.
- Published
- 2021
35. The Impact of Breast Cancer Treatment Delays on Survival Among South African Women
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Yoanna S Pumpalova, Oluwatosin A Ayeni, Wenlong Carl Chen, Ines Buccimazza, Sharon Cačala, Laura W Stopforth, Hayley A Farrow, Witness Mapanga, Sarah Nietz, Boitumelo Phakathi, Maureen Joffe, Valerie McCormack, Judith S Jacobson, Katherine D Crew, Alfred I Neugut, Paul Ruff, Herbert Cubasch, and Daniel S O’Neil
- Subjects
Male ,Cancer Research ,South Africa ,Oncology ,Chemotherapy, Adjuvant ,Humans ,Breast Neoplasms ,Female ,Neoadjuvant Therapy ,Proportional Hazards Models - Abstract
Background In high-income settings, delays from breast cancer (BC) diagnosis to initial treatment worsen overall survival (OS). We examined how time to BC treatment initiation (TTI) impacts OS in South Africa (SA). Methods We evaluated women enrolled in the South African BC and HIV Outcomes study between July 1, 2015 and June 30, 2019, selecting women with stages I-III BC who received surgery and chemotherapy. We constructed a linear regression model estimating the impact of sociodemographic and clinical factors on TTI and separate multivariable Cox proportional hazard models by first treatment (surgery and neoadjuvant chemotherapy (NAC)) assessing the effect of TTI (in 30-day increments) on OS. Results Of 1260 women, 45.6% had upfront surgery, 54.4% had NAC, and 19.5% initiated treatment >90 days after BC diagnosis. Compared to the surgery group, more women in the NAC group had stage III BC (34.8% vs 81.5%). Living further away from a hospital and having hormone receptor positive (vs negative) BC was associated with longer TTI (8 additional days per 100 km, P = .003 and 8 additional days, P = .01, respectively), while Ki67 proliferation index >20 and upfront surgery (vs NAC) was associated with shorter TTI (12 and 9 days earlier; P = .0001 and.007, respectively). Treatment initiation also differed among treating hospitals (P < .0001). Additional 30-day treatment delays were associated with worse survival in the surgery group (HR 1.11 [95%CI 1.003-1.22]), but not in the NAC group. Conclusions Delays in BC treatment initiation are common in SA public hospitals and are associated with worse survival among women treated with upfront surgery.
- Published
- 2021
36. A concise review towards defining the exposome of oesophageal cancer in sub-Saharan Africa
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Sarah De Saeger, Marthe De Boevre, Valerie McCormack, Trancizeo Lipenga, Zdenko Herceg, Limbikani Matumba, and Arnau Vidal
- Subjects
Exposome ,medicine.medical_specialty ,Sub saharan ,Esophageal Neoplasms ,Context (language use) ,ALCOHOL ,POLYCYCLIC AROMATIC-HYDROCARBONS ,Environmental health ,Epidemiology ,Medicine and Health Sciences ,Medicine ,Humans ,GE1-350 ,GENETIC POLYMORPHISMS ,Africa South of the Sahara ,General Environmental Science ,TOBACCO ,business.industry ,Oesophageal cancer ,Incidence ,AREA ,HUMAN-PAPILLOMAVIRUS ,Cancer ,CONSUMPTION ,ASSOCIATION ,Oesophageal squamous cell carcinoma ,medicine.disease ,digestive system diseases ,Environmental sciences ,HIGH-RISK ,Africa ,Etiology ,SQUAMOUS-CELL CARCINOMA ,Esophageal Squamous Cell Carcinoma ,business ,Evidence synthesis ,GASTRIC-CANCER ,Cohort study - Abstract
Context Oesophageal cancer (EC) is among the common causes of illness and death among all cancers worldwide. Advanced EC has a poor prognosis, with worse outcomes observed in low-income settings. Oesophageal squamous cell carcinoma (ESCC) is the most common EC histology reported globally, with the highest ESCC incidence rates in the ‘Asian Belt’ and the African EC corridor. While the aetiology of ESCC is well-documented in the ‘Asian belt’, data for the African EC corridor and the entirety of sub-Saharan Africa (SSA) are fewer. Objective To help address gaps in ESCC aetiology in SSA, we critically evaluated evidence of lifestyle, environmental, and epigenetic factors associated with ESCC risk and discussed prospects of defining ESCC exposome. Data inclusion Unlimited English and non-English articles search were made on PubMed Central and Web of Science databases from January 1970 to August 2021. In total, we retrieved 999 articles and considered meta-analyses, case-control, and cohort studies. The quality of individual studies was assessed using the Newcastle–Ottawa scale. Data extraction Details extracted include the year of publication, country of origin, sample size, comparators, outcomes, study subjects, and designs. Data analysis Together, we assessed 13 case-control studies and two meta-analyses for the effect of lifestyle or environmental exposures on ESCC risk. Again, we evaluated seven case-control studies and one meta-analysis regarding the role of epigenetics in ESCC tumorigenesis. Results In general, evidence of ESCC aetiology points to essential contributions of alcohol, tobacco, hot beverages, biomass fuel, and poor oral health/hygiene, although more precise risk characterisation remains necessary. Conclusion We conclude that ESCC in SSA is a multifactorial disease initiated by several external exposures that may induce aberrant epigenetic changes. The expanding aetiological research in this domain will be enhanced by evidence synthesis from classical and molecular epidemiological studies spanning the external and internal exposome.
- Published
- 2021
37. Mutational signatures in esophageal squamous cell carcinoma from eight countries of varying incidence
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Jean-Yves Scoazec, S M Ashiqul Islam, Irina I. Abnizova, Diana Menya, Paul Richman, Dariush Nasrollahzadeh, Michael R. Stratton, Charles Dzamalala, Sergey Senkin, Karl Smith-Byrne, Hiva Saffar, Pauline E Bucciarelli, Christine Carreira, Sarah Moody, Michael Eden, Paul Brennan, Yudou He, Lia S Campos, Azhar Khandekar, Erik N. Bergstrom, Arash Nikmanesh, Abdolreza Fazel, Ghislaine Scelo, Valerie Gaborieau, Farid Azmoudeh-Ardelan, Calli Latimer, Ricardo Cortez Cardoso Penha, Laura Humphreys, Stefano Serra, Jon W. Teague, Tatsuhiro Shibata, Ludmil B. Alexandrov, Estelle Chanudet, Masoud Sotoudeh, Jingwei Wang, Blandina T. Mmbaga, Valerie McCormack, Reza Malekzadeh, Rebecca C. Fitzgerald, Joshua R. Atkins, David T. Jones, Sandra Perdomo, Emily Thomas, Luis Felipe Ribeiro, Alisa M. Goldstein, Stephen Fitzgerald, Behnoush Abedi-Ardekani, James McKay, and Nan Hu
- Subjects
APOBEC ,Mutation ,Environmental risk ,Incidence (epidemiology) ,Epidemiology of cancer ,medicine ,Cancer research ,Biology ,medicine.disease_cause ,neoplasms ,Esophageal squamous cell carcinoma ,digestive system diseases ,Germline - Abstract
Esophageal squamous cell carcinoma (ESCC) shows a remarkable variation in incidence which is not fully explained by known lifestyle and environmental risk factors. It has been speculated that an unknown exogenous exposure(s) could be responsible. Here we combine the fields of mutational signature analysis with cancer epidemiology to study 552 ESCC genomes from eight countries with varying incidence rates. The mutational profiles of ESCC were similar across all countries studied. Associations between specific mutational signatures and ESCC risk factors were identified for tobacco, alcohol, opium and germline variants, with modest impacts on mutation burden. We find no evidence of a mutational signature indicative of an exogenous exposure capable of explaining the differences in ESCC incidence. APOBEC associated mutational signatures SBS2 and SBS13 were present in 88% and 91% of cases respectively and accounted for a quarter of the mutation burden on average, indicating that activation of APOBEC is a crucial step in ESCC tumor development.
- Published
- 2021
38. Environmental geochemistry and cancer: a pertinent global health problem requiring interdisciplinary collaboration
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Joachim Schüz, Michael J. Watts, Valerie McCormack, and Daniel R. S. Middleton
- Subjects
medicine.medical_specialty ,Livestock ,Environmental Engineering ,Esophageal Neoplasms ,010504 meteorology & atmospheric sciences ,Disease ,010501 environmental sciences ,Global Health ,01 natural sciences ,Environmental geochemistry ,Geochemistry and Petrology ,Neoplasms ,Environmental health ,Epidemiology of cancer ,medicine ,Global health ,Animals ,Humans ,Environmental Chemistry ,0105 earth and related environmental sciences ,General Environmental Science ,Water Science and Technology ,Public health ,Animal disease ,Cancer ,Subsistence agriculture ,Environmental Exposure ,General Medicine ,Africa, Eastern ,medicine.disease ,Geography ,Environmental Science ,Carcinogens ,Environmental Monitoring - Abstract
Primary prevention is a key strategy to reducing the global burden of cancer, a disease responsible for ~ 9.6 million deaths per year and predicted to top 13 million by 2030. The role of environmental geochemistry in the aetiology of many cancers-as well as other non-communicable diseases-should not be understated, particularly in low- and middle-income countries where 70% of global cancer deaths occur and reliance on local geochemistry for drinking water and subsistence crops is still widespread. This article is an expansion of a series of presentations and discussions held at the 34th International Conference of the Society for Environmental Geochemistry and Health in Livingstone, Zambia, on the value of effective collaborations between environmental geochemists and cancer epidemiologists. Key technical aspects of each field are presented, in addition to a case study of the extraordinarily high incidence rates of oesophageal cancer in the East African Rift Valley, which may have a geochemical contribution. The potential merit of veterinary studies for investigating common geochemical risk factors between human and animal disease is also highlighted.
- Published
- 2019
39. Awareness of Cancer Risk Factors and Its Signs and Symptoms in Northern Tanzania: a Cross-Sectional Survey in the General Population and in People Living with HIV
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Oresto Michael Munishi, Frank Kimaro, Charles Muiruri, Francis Karia, Pilli Nyindo, Valerie McCormack, Oscar Mapunda, Glory Mangi, Bariki Mchome, Theresia Namwai, Leah L. Zullig, Blandina T. Mmbaga, and John Bartlett
- Subjects
Adult ,Male ,Health Knowledge, Attitudes, Practice ,Modern medicine ,Cancer signs and symptoms ,Cross-sectional study ,Population ,HIV Infections ,Tanzania ,Article ,03 medical and health sciences ,0302 clinical medicine ,Risk Factors ,Interquartile range ,Neoplasms ,Surveys and Questionnaires ,Community cancer risk awareness ,Humans ,Medicine ,030212 general & internal medicine ,education ,education.field_of_study ,biology ,business.industry ,Public Health, Environmental and Occupational Health ,HIV ,Cancer ,Middle Aged ,biology.organism_classification ,medicine.disease ,Cross-Sectional Studies ,Oncology ,030220 oncology & carcinogenesis ,Female ,business ,Cancer risk ,Demography - Abstract
An important component of cancer control programs for the growing burden in sub-Saharan Africa is a population’s awareness of risk factors. Studies thereof have focused on single rather than multiple cancers and carcinogens. During March and April 2015, we undertook a survey to assess awareness of multiple cancer risk factors and symptoms in the Kilimanjaro Region, North Tanzania. General population (n = 620) and attendees at HIV care-and-treatment clinics (CTCs) were included (n = 207). Participants’ mean age was 43.8 (interquartile range 30–52) years; 58% were female. Awareness of cancer risk was highest for tobacco (90%) and alcoholic spirits (67%), but tended to be lower for infections (41% for HIV (42.2% and 41.4% for CTC and community group, respectively) and 16% for HPV (16.0% and 16.6% for CTC and community group, respectively)), while that of moldy maize and peanuts was 35% for both. Awareness of specific cancer signs and symptoms ranged between 70% and 90%. Awareness of alcohol and tobacco was higher in men than women (odds ratio = 1.82 (1.38, 2.40) and 3.96 (2.14, 7.31), respectively). In relation to cancer treatment, 70% preferred modern medicine and 10% preferred traditional medicine alone. Sixty percent was not aware of any local cancer early detection services. Only 20% had ever been examined for cancer, and of those screened, CTC group was 1.5 times more likely to screen than community participants. Awareness did not differ by age or HIV status. There are good levels of cancer risk factor awareness for certain lifestyle-related carcinogens in Tanzania; however, increased awareness is needed especially for infections and cancer warning symptom both in the general and HIV-positive population, as well as some myths to be dispelled.
- Published
- 2019
40. Abstract P5-13-01: Not presented
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Charles Adisa, I dos Santos Silva, Valerie McCormack, Milena Foerster, M Galakunde, Angelica Anele, Annelle Zietsman, and Joachim Schüz
- Subjects
Cancer Research ,Oncology - Abstract
This abstract was not presented at the conference. Citation Format: Foerster M, Zietsman A, Galakunde M, Anele A, Adisa C, Schuz J, Dos Santos Silva I, McCormack V. Not presented [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr P5-13-01.
- Published
- 2019
41. The evidence gap between alcohol consumption and oesophageal squamous cell carcinoma in east Africa – Authors' reply
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Valerie, McCormack, Daniel R S, Middleton, Blandina T, Mmbaga, Diana, Menya, Charles, Dzamalala, Gissela, Nyakunga-Maro, Peter, Finch, Yohannie, Mlombe, and Joachim, Schüz
- Subjects
Alcohol Drinking ,Esophageal Neoplasms ,Risk Factors ,Humans ,Esophageal Squamous Cell Carcinoma ,General Medicine ,Africa, Eastern - Published
- 2022
42. Cancer epidemiology fieldwork in a resource-limited setting: Experience from the western Kenya ESCCAPE esophageal cancer case-control pilot study
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Stephen K. Maina, Behnoush Abebi-Ardekani, Rafael S. Carel, Caroline Kibosia, Fatma Some, David Chumba, Diana Menya, Daniel R. S. Middleton, Nicholas Kigen, Valerie McCormack, Margaret Oduor, Florence A. Murgor, and Joachim Schüz
- Subjects
Male ,0301 basic medicine ,Cancer Research ,medicine.medical_specialty ,Esophageal Neoplasms ,Referral ,Epidemiology ,media_common.quotation_subject ,Pilot Projects ,Article ,03 medical and health sciences ,0302 clinical medicine ,Surveys and Questionnaires ,Health care ,Epidemiology of cancer ,medicine ,Information system ,Humans ,Attrition ,Developing Countries ,media_common ,Selection bias ,business.industry ,Cancer ,medicine.disease ,Kenya ,030104 developmental biology ,Oncology ,Research Design ,Case-Control Studies ,030220 oncology & carcinogenesis ,Data quality ,Family medicine ,Female ,Esophageal Squamous Cell Carcinoma ,Epidemiologic Methods ,business - Abstract
Background Case-control studies remain an important study design for aetiologic research on cancer, particularly when cohorts are not available. In addition to the potential biases inherent in this design, conducting fieldwork in settings with weak health care and information systems for cancer, such as in sub Saharan Africa, confer additional challenges which we present here with the aim to share experience to guide future studies. Methods We undertook a hospital-based case-control study of squamous cell esophageal cancer at the Moi Teaching and Referral Hospital in Eldoret, West Kenya. Cases were recruited at endoscopy and controls from hospital wards, age and gender frequency-matched to cases. Urine, toenails, blood and tumour biopsy were collected and a questionnaire administered. Results During this pilot phase, 143 cases and 155 controls were successfully recruited. Complete questionnaire data was obtained through e-data collection. Biospecimen collection was possible with support of an already existing equipped laboratory. We introduce changes made in the main study phase, including on expansion of the control groups to allow to consideration of selection bias. Conclusions Extra attention and funding to train and monitor data quality and biospecimen collection and collaboration of a large group held together by strong leadership are essential. We recommend studies based on regional treatment centres with their more defined catchment areas rather than in the capital cities as referral routes in multi-level health care systems are severely attrition prone.
- Published
- 2018
43. Minimally invasive esophageal sponge cytology sampling is feasible in a Tanzanian community setting
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Rehema M Minde, Martin Bromwich, M O'Donovan, Venance P. Maro, Valerie McCormack, Daniel R. S. Middleton, Irene Debiram-Beecham, Behnoush Abedi-Ardekani, Amos Mwasamwaja, Gissela Nyakunga-Maro, Joachim Schüz, Timothy Ngowi, Blandina T. Mmbaga, Rebecca C. Fitzgerald, Amini Daudi, Alex Mremi, Jackson P Claver, Middleton, Daniel RS [0000-0003-2450-8610], McCormack, Valerie [0000-0001-7397-3442], and Apollo - University of Cambridge Repository
- Subjects
Adult ,Male ,Cancer Research ,medicine.medical_specialty ,Esophageal Neoplasms ,Cytodiagnosis ,Context (language use) ,Asymptomatic ,Specimen Handling ,03 medical and health sciences ,0302 clinical medicine ,Internal medicine ,Epidemiology ,medicine ,Humans ,Sampling (medicine) ,esophageal cancer ,Aged ,business.industry ,Intestinal metaplasia ,Middle Aged ,medicine.disease ,squamous dysplasia ,Cytosponge ,Oncology ,Dysplasia ,030220 oncology & carcinogenesis ,Africa ,Etiology ,Adenocarcinoma ,Female ,Esophageal Squamous Cell Carcinoma ,medicine.symptom ,business ,Precancerous Conditions - Abstract
Esophageal sponge cytology is an endoscopy alternative well accepted by patients with extensive data for accuracy in the context of adenocarcinoma. Few studies have assessed its feasibility in asymptomatic community members, and fewer still in East Africa, where esophageal squamous cell carcinoma (ESCC) rates are high. We aimed to assess the feasibility of a capsule-based diagnosis of esophageal squamous dysplasia (ESD), an ESCC precursor, which may benefit epidemiological and early detection research. We collected Cytosponge collections in 102 asymptomatic adults from Kilimanjaro, Tanzania. Uptake, acceptability and safety were assessed. Participants scored acceptability immediately following the procedure and 7 days later on a scale of 0 (least) to 10 (most acceptable). Slides from paraffin-embedded cell clots were read by two pathologists for ESD and other pathologies. All participants (52 men, 50 women, aged 30-77) swallowed the device at first attempt, 100 (98%) of which gave slides of adequate cellularity. Acceptability scores were 10 (53%), 9 (24%), 8 (21%), 7 (2%) and 6 (1%), with no differences by age, sex or time of asking. Cytological findings were esophageal inflammation (4%), atypical squamous cells of uncertain significance (1%), low-grade dysplasia (1%), gastritis (22%) and suspected intestinal metaplasia (6%). Setting-specific logistical and ethical considerations of study implementation are discussed. We demonstrate the safety, acceptability and feasibility of Cytosponge sampling in this setting, paving the way for innovative etiology and early-detection research. Targeted sampling strategies and biomarker development will underpin the success of such initiatives. The study protocol is registered on ClinicalTrials.gov (NCT04090554).
- Published
- 2021
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44. Breast Cancer Survival Disparities between HIV+ Compared to HIV- Women Across Different Patient and Tumour Characteristics and Diverse Sub-Saharan African Settings
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Isabel dos-Santos-Silva, Moses Galukande, Milena Foerster, Angelica Anele, Awa Ukonye Offiah, Charles Adisa, Valerie McCormack, Leeya F. Pinder, Benjamin O. Anderson, Maureen Joffe, Steady Chasimpha, Herbert Cubasch, Annelle Zietsman, Joachim Schüz, Pauline Boucheron, and Groesbeck P. Parham
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Breast cancer ,business.industry ,Informed consent ,Proportional hazards model ,Hazard ratio ,Cohort ,Medicine ,Cancer ,Disease ,business ,medicine.disease ,Prospective cohort study ,Demography - Abstract
Background: Studies have shown increased mortality among HIV-positive women with breast cancer compared to HIV-negative women with breast cancer, but none has examined how this differential varies by patient or breast tumour characteristics. Methods: ABC-DO study is a prospective cohort of incident breast cancer women recruited at diagnosis (2014-2017) in Namibia, Nigeria, South Africa, Uganda and Zambia. Detailed clinic-epidemiological data were collected at baseline. Participants were actively followed-up via 3-monthly telephone calls. Using Cox regression, we examined differences in overall survival by HIV status in the cohort, and across country and patient subgroups, adjusted for age at cancer diagnosis, tumour grade and stage at cancer diagnosis. Findings: Among 1,635 women, 313 (19%) were HIV-positive, 1,184 (72%) were HIV-negative and 138 (9%) HIV-unknown. At breast cancer diagnosis, HIV-positive women were younger and had lower BMI than their HIV-negative counterparts, but had similar tumour stage, grade and receptor subtypes. At the end of the follow-up (January 1, 2019), a higher proportion of HIV-positive women (137 (44%)) had died compared to HIV-negative women (432 (37%)). Crude three-year survival was 9% lower for HIV-positive women (46% vs. 55% for HIV-negative women, hazard ratio (HR) 1·41; 95% CI: 1·15-1·74). The difference did not differ by age, BMI, tumour subtype or grade but was stronger in women with non-metastatic disease (52% HIV-positive vs. 63% HIV-negative women, adjusted HR 1·65: 1·30-2·10), whilst women with metastatic cancer had low survival regardless of HIV status. Interpretation: The larger survival deficit among WLWH with non-metastatic breast cancer calls for a better understanding of the reasons underlying this differential e.g. biological mechanisms, health behaviours, detrimental HIV-breast cancer treatment interactions or higher HIV background mortality, to inform strategies for reducing mortality among this young patient group. Funding: Susan G Komen, International Agency for Research on Cancer, National Cancer Institute and UK-Commonwealth Scholarships. Declaration of Interest: No declaration of competing interests. Ethical Approval: The ABC-DO study was approved by all institutional ethics committees (List 1 in Supplementary Material), and all women provided written or thumbprint informed consent, witnessed by the study interviewer.
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- 2021
45. Maternally Orphaned Children and Intergenerational Concerns Associated With Breast Cancer Deaths Among Women in Sub-Saharan Africa
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Charles Adisa, Valerie McCormack, Benjamin O. Anderson, Leeya F. Pinder, Isabel dos-Santos-Silva, Anna Cabanes, Milena Foerster, Angelica Anele, Moses Galukande, Joachim Schüz, Groesbeck P. Parham, Annelle Zietsman, Dorothy Lombe, and Songiso Mutumba
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Cancer Research ,Sub saharan ,Next of kin ,Adolescent ,Breast Neoplasms ,Cohort Studies ,03 medical and health sciences ,0302 clinical medicine ,Breast cancer ,parasitic diseases ,medicine ,Online First ,Humans ,Family ,Breast ,030212 general & internal medicine ,Child ,Africa South of the Sahara ,Black women ,business.industry ,Research ,Brief Report ,Cancer ,medicine.disease ,Oncology ,030220 oncology & carcinogenesis ,Child, Preschool ,Cohort ,Maternal death ,Female ,business ,Child, Orphaned ,Comments ,Demography ,Cohort study - Abstract
Key Points Question How many maternal orphans resulted from every 100 breast cancer deaths in sub-Saharan African settings in 2014-2019? Findings In the African Breast Cancer–Disparities in Outcomes cohort study of women with breast cancer, there were 964 children (, Importance Low breast cancer survival in sub-Saharan Africa’s young population increases the likelihood that breast cancer deaths result in maternal orphans, ie, children (, This cohort study estimates the number of maternal orphans in 4 sub-Saharan Africa countries when women die of breast cancer.
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- 2020
46. Household Air Pollution (HAP) and Esophageal Squamous Cell Carcinoma: findings from a case-control study in Western Kenya
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Diana Menya, Elisa Puzzolo, Iva Čukić, Valerie McCormack, and D. Pople
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Oncology ,medicine.medical_specialty ,business.industry ,Internal medicine ,Case-control study ,General Earth and Planetary Sciences ,Medicine ,Cancer ,Esophageal cancer ,business ,medicine.disease ,Esophageal squamous cell carcinoma ,General Environmental Science - Abstract
Background/Aim. Esophageal Cancer (EC) is the most common cancer in Kenya with age standardised rates of 17.6 per 100,000 in both sexes, compared to 5.9 worldwide. Traditional risk factors (e.g. sm...
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- 2020
47. Genome-Wide DNA Methylation Profiling of Esophageal Squamous Cell Carcinoma from Global High-Incidence Regions Identifies Crucial Genes and Potential Cancer Markers
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Behnoush Abedi-Ardekani, Christine Carreira, Diana Menya, Anne Claire Boisson, Fazlur Rahman Talukdar, Mona Ellaithi, Cyrille Cuenin, Florence Le Calvez-Kelm, Maria Leon Roux, Akram Ghantous, Bruna Pereira Sorroche, Daniel R. S. Middleton, Joachim Schüz, Rui Henrique, Valerie McCormack, Nitin Gangane, M. Iqbal Parker, Reza Malekzadeh, Charles Dzamalala, Luis Felipe Ribeiro Pinto, Carmen Jerónimo, Ruhina Shirin Laskar, Abraham Aseffa, Sheila Coelho Soares Lima, Vera Miranda-Gonçalves, Zdenko Herceg, Mathewos Assefa, Nagla Gasmelseed, Ramin Shakeri, and Rita Khoueiry
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0301 basic medicine ,Adult ,Male ,Cancer Research ,Esophageal Neoplasms ,Biology ,Global Health ,Genome ,Epigenesis, Genetic ,03 medical and health sciences ,0302 clinical medicine ,medicine ,Biomarkers, Tumor ,Humans ,Epigenetics ,Biomarker discovery ,Gene ,Aged ,Aged, 80 and over ,Genome, Human ,Incidence ,Cancer ,Promoter ,Methylation ,DNA, Neoplasm ,DNA Methylation ,Middle Aged ,medicine.disease ,Prognosis ,Gene Expression Regulation, Neoplastic ,030104 developmental biology ,Oncology ,030220 oncology & carcinogenesis ,Case-Control Studies ,DNA methylation ,Cancer research ,Female ,Esophageal Squamous Cell Carcinoma ,Follow-Up Studies - Abstract
Epigenetic mechanisms such as aberrant DNA methylation (DNAme) are known to drive esophageal squamous cell carcinoma (ESCC), yet they remain poorly understood. Here, we studied tumor-specific DNAme in ESCC cases from nine high-incidence countries of Africa, Asia, and South America. Infinium MethylationEPIC array was performed on 108 tumors and 51 normal tissues adjacent to the tumors (NAT) in the discovery phase, and targeted pyrosequencing was performed on 132 tumors and 36 NAT in the replication phase. Top genes for replication were prioritized by weighting methylation results using RNA-sequencing data from The Cancer Genome Atlas and GTEx and validated by qPCR. Methylome analysis comparing tumor and NAT identified 6,796 differentially methylated positions (DMP) and 866 differential methylated regions (DMR), with a 30% methylation (Δβ) difference. The majority of identified DMPs and DMRs were hypermethylated in tumors, particularly in promoters and gene-body regions of genes involved in transcription activation. The top three prioritized genes for replication, PAX9, SIM2, and THSD4, had similar methylation differences in the discovery and replication sets. These genes were exclusively expressed in normal esophageal tissues in GTEx and downregulated in tumors. The specificity and sensitivity of these DNAme events in discriminating tumors from NAT were assessed. Our study identified novel, robust, and crucial tumor-specific DNAme events in ESCC tumors across several high-incidence populations of the world. Methylome changes identified in this study may serve as potential targets for biomarker discovery and warrant further functional characterization. Significance: This largest genome-wide DNA methylation study on ESCC from high-incidence populations of the world identifies functionally relevant and robust DNAme events that could serve as potential tumor-specific markers.
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- 2020
48. Geospatial barriers to healthcare access for breast cancer diagnosis in sub-Saharan African settings: The African Breast Cancer-Disparities in Outcomes Cohort Study
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Angelica Anele, Moses Galukande, Annelle Zietsman, Joachim Schüz, Fiona McKenzie, Groesbeck P. Parham, Valerie McCormack, Johanna Pontac, Milena Foerster, Leeya F. Pinder, Kayo Togawa, Charles Adisa, Benjamin O. Anderson, and Isabel dos Santos‐Silva
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Cancer Research ,Population ,Breast Neoplasms ,geospatial barrier ,Logistic regression ,Cohort Studies ,03 medical and health sciences ,0302 clinical medicine ,Breast cancer ,breast cancer ,Interquartile range ,Outcome Assessment, Health Care ,medicine ,cohort study ,Humans ,Prospective Studies ,Healthcare Disparities ,education ,Prospective cohort study ,Africa South of the Sahara ,education.field_of_study ,business.industry ,Odds ratio ,medicine.disease ,Oncology ,Quartile ,030220 oncology & carcinogenesis ,Female ,business ,Cancer Epidemiology ,sub‐Saharan Africa ,Demography ,Cohort study ,early diagnosis - Abstract
We examined the geospatial dimension of delays to diagnosis of breast cancer in a prospective study of 1541 women newly diagnosed in the African Breast Cancer—Disparities in Outcomes (ABC‐DO) Study. Women were recruited at cancer treatment facilities in Namibia, Nigeria, Uganda and Zambia. The baseline interview included information used to generate the geospatial features: urban/rural residence, travel mode to treatment facility and straight‐line distances from home to first‐care provider and to diagnostic/treatment facility, categorized into country/ethnicity (population)‐specific quartiles. These factors were investigated in relation to delay in diagnosis (≥3 months since first symptom) and late stage at diagnosis (TNM: III, IV) using logistic regression, adjusted for population group and sociodemographic characteristics. The median (interquartile range) distances to first provider and diagnostic and treatment facilities were 5 (1‐37), 17 (3‐105) and 62 (5‐289) km, respectively. The majority had a delay in diagnosis (74%) and diagnosis at late stage (64%). Distance to first provider was not associated with delay in diagnosis or late stage at diagnosis. Rural residence was associated with delay, but the association did not persist after adjustment for sociodemographic characteristics. Distance to the diagnostic/treatment facility was associated with delay (highest vs lowest quartile: odds ratio (OR) = 1.56, 95% confidence interval (CI) = 1.08‐2.27) and late stage (overall: OR = 1.47, CI = 1.05‐2.06; without Nigerian hospitals where mostly local residents were treated: OR = 1.73, CI = 1.18‐2.54). These findings underscore the need for measures addressing the geospatial barriers to early diagnosis in sub‐Saharan African settings, including providing transport or travel allowance and decentralizing diagnostic services., What's new? Survival from breast cancer is poor in sub‐Saharan Africa, due largely to the high proportion of women who are diagnosed at advanced stages. In this study, the authors examined geospatial information to assess women's prediagnostic journey to breast cancer diagnosis, with special attention to delays in diagnosis, in the regions of Namibia, Nigeria, Uganda, and Zambia. Geospatial factors particularly long travel distances to diagnostic and treatment facilities were identified as major barriers to early diagnosis. The findings underscore the need for policies to address these barriers to ensure breast cancer diagnosis at a curable stage.
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- 2020
49. Missing and decayed teeth, oral hygiene and dental staining in relation to esophageal cancer risk: ESCCAPE case-control study in Kilimanjaro, Tanzania
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Alex Mremi, Eliawawomy Mghase, Godfrey Mushi, Amos Mwasamwaja, Behnoush Abedi-Ardekani, Valerie McCormack, Kajiru Kilonzo, Amana Mchome, Blandina T. Mmbaga, Ireen Kiwelu, Daniel R. S. Middleton, Remigi Swai, Joachim Schüz, Oresto Michael Munishi, Evarista Mallya, Deogratias Stanslaus Rwakatema, Godwin Kiwelu, Redfan Shao, Gissela Nyakunga, and Sophia Mustapha
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Cancer Research ,Decayed teeth ,Dentistry ,Oral health ,Oral hygiene ,Tanzania ,03 medical and health sciences ,0302 clinical medicine ,stomatognathic system ,Medicine ,esophageal cancer ,biology ,fluorosis ,business.industry ,Case-control study ,Odds ratio ,Esophageal cancer ,medicine.disease ,biology.organism_classification ,stomatognathic diseases ,Oncology ,030220 oncology & carcinogenesis ,oral health ,business ,Dental fluorosis ,Cancer Epidemiology - Abstract
In the African esophageal squamous cell carcinoma (ESCC) corridor, recent work from Kenya found increased ESCC risk associated with poor oral health, including an ill‐understood association with dental fluorosis. We examined these associations in a Tanzanian study, which included examination of potential biases influencing the latter association. This age and sex frequency‐matched case‐control study included 310 ESCC cases and 313 hospital visitor/patient controls. Exposures included self‐reported oral hygiene and nondental observer assessed decayed+missing+filled tooth count (DMFT index) and the Thylstrup‐Fejerskov dental fluorosis index (TFI). Blind to this nondental observer TFI, a dentist independently assessed fluorosis on photographs of 75 participants. Odds ratios (ORs) are adjusted for demographic factors, alcohol and tobacco. ESCC risk was associated with using a chewed stick to brush teeth (OR 2.3 [95% CI: 1.3‐4.1]), using charcoal to whiten teeth (OR 2.13 [95% CI: 1.3, 4.1]) and linearly with the DMFT index (OR 3.3 95% CI: [1.8, 6.0] for ≥10 vs 0). Nondental observer‐assessed fluorosis was strongly associated with ESCC risk (OR 13.5 [95% CI: 5.7‐31.9] for TFI 5+ v 0). However, the professional dentist's assessment indicated that only 43% (10/23) of participants assessed as TFI 5+ actually had fluorosis. In summary, using oral charcoal, brushing with a chewed stick and missing/decayed teeth may be risk factors for ESCC in Tanzania, for which dose‐response and mechanistic research is needed. Links of ESCC with “dental fluorosis” suffered from severe exposure misclassification, rendering it impossible to disentangle any effects of fluorosis, extrinsic staining or reverse causality., What's new? The putative etiological model for the African oesophageal cancer corridor involves a combination of unknown spatially‐patterned factors and lifestyle factors such as poor oral health. The association of oesophageal cancer with dental fluorosis in Kenya, in addition to expected associations with dental decay/loss, recently raised intrigue. In the present Tanzanian case‐control study, findings were consistent with those from Kenya. However, a review of oral photographs indicated serious fluorosis exposure misclassification, rendering it impossible to disentangle any effects of fluorosis, extrinsic staining, or reverse causality.
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- 2020
50. Expert Discussion: Breast Cancer in Low-Resource Countries
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Lydia E. Pace, Ahmedin Jemal, Eva Johanna Kantelhardt, Herbert Cubasch, Valerie McCormack, and Mathewos Assefa
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medicine.medical_specialty ,Text mining ,Breast cancer ,Oncology ,business.industry ,Low resource ,Family medicine ,medicine ,MEDLINE ,Surgery ,business ,medicine.disease ,Expert Discussion - Published
- 2020
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