Collaborative Molecular Epidemiology Study of Metabolic Dysregulation, DNA Methylation, and Breast Cancer Risk Among Nigerian Women: MEND Study Objectives and Design

PURPOSE To elucidate the role of metabolic dysregulation and associated DNA methylation changes on breast cancer risk and aggressive subtypes among Nigerian women. We describe the design and methods of a collaborative molecular epidemiology study of breast cancer in Nigerian hospitals. METHODS The Mechanisms for Novel and Established Risk Factors for Breast Cancer in Women of Nigerian Descent (MEND) study was designed as a matched case-control study of 350 patients, age 18 to 75 years, with newly diagnosed, treatment-naive breast cancer and 350 age-matched healthy controls from surrounding geographic areas. Patients with breast cancer seen for initial diagnosis at four large tertiary hospitals in southwest Nigeria and one affiliated private hospital were recruited. Healthy female controls were selected from a cohort of 4,000 healthy women recruited as part of the Human Heredity and Health (H3) in Africa Chronic Kidney Disease Case-Control Study in Nigeria. Tumor and adjacent normal tissue, and blood and saliva samples were collected for molecular and epigenetic assays. RESULTS Although recruitment is ongoing, a total of 416 patients have been recruited to date, with tumor and blood samples obtained from at least 310 patients. Data on age-matched (6 months) controls have also been obtained and harmonized. Lipid assays for 350 pathologically verified cases and 350 age-matched controls is underway, and pathologic characterization of tumors (including immunohistochemistry for subtyping) is ongoing. Data on DNA methylation for tumors and adjacent normal tissue are expected by the end of the study period. CONCLUSION The MEND study will provide a unique, high-quality source of data to evaluate the contribution of metabolic dysregulation such as obesity, diabetes, hypertension, and metabolic syndrome to the biology of breast cancer among Nigerian women and foster collaborative studies relevant for women of African descent globally. J Global Oncol. (C) 2019 by American Society of Clinical Oncology.National Institutes of Health, National Cancer Institute, Fogarty International Center [K01TW010271]Open access journalThis item from the UA Faculty Publications collection is made available by the University of Arizona with support from the University of Arizona Libraries. If you have questions, please contact us at [email protected]

Collaborative Molecular Epidemiology Study of Metabolic Dysregulation, DNA Methylation, and Breast Cancer Risk Among Nigerian Women: MEND Study Objectives and Design

PURPOSE To elucidate the role of metabolic dysregulation and associated DNA methylation changes on breast cancer risk and aggressive subtypes among Nigerian women. We describe the design and methods of a collaborative molecular epidemiology study of breast cancer in Nigerian hospitals. METHODS The Mechanisms for Novel and Established Risk Factors for Breast Cancer in Women of Nigerian Descent (MEND) study was designed as a matched case-control study of 350 patients, age 18 to 75 years, with newly diagnosed, treatment-naïve breast cancer and 350 age-matched healthy controls from surrounding geographic areas. Patients with breast cancer seen for initial diagnosis at four large tertiary hospitals in southwest Nigeria and one affiliated private hospital were recruited. Healthy female controls were selected from a cohort of 4,000 healthy women recruited as part of the Human Heredity and Health (H3) in Africa Chronic Kidney Disease Case-Control Study in Nigeria. Tumor and adjacent normal tissue, and blood and saliva samples were collected for molecular and epigenetic assays. RESULTS Although recruitment is ongoing, a total of 416 patients have been recruited to date, with tumor and blood samples obtained from at least 310 patients. Data on age-matched (± 6 months) controls have also been obtained and harmonized. Lipid assays for 350 pathologically verified cases and 350 age-matched controls is underway, and pathologic characterization of tumors (including immunohistochemistry for subtyping) is ongoing. Data on DNA methylation for tumors and adjacent normal tissue are expected by the end of the study period. CONCLUSION The MEND study will provide a unique, high-quality source of data to evaluate the contribution of metabolic dysregulation such as obesity, diabetes, hypertension, and metabolic syndrome to the biology of breast cancer among Nigerian women and foster collaborative studies relevant for women of African descent globally

Association of Body Composition with Odds of Breast Cancer by Molecular Subtype: Analysis of the Mechanisms for Established and Novel Risk Factors for Breast Cancer in Nigerian Women (MEND) Study

BACKGROUND: The association between obesity and breast cancer (BC) has been extensively studied among US, European and Asian study populations, with often conflicting evidence. However, despite the increasing prevalence of obesity and associated conditions in Africa, the continent with the highest age-standardized BC mortality rate globally, few studies have evaluated this association, and none has examined in relation to molecular subtypes among African women. The current analysis examines the association between body composition, defined by body mass index (BMI), height, and weight, and BC by molecular subtype among African women. METHODS: We estimated odds ratios (ORs) and 95% confidence intervals (95% CI) for the association between measures of body composition and BC and molecular subtypes among 419 histologically confirmed cases of BC and 286 healthy controls from the Mechanisms for Established and Novel Risk Factors for Breast Cancer in Women of Nigerian Descent (MEND) case-control study. RESULTS: Higher BMI (aOR: 0.79; 95% CI: 0.67, 0.95) and weight (aOR: 0.83; 95% CI: 0.69, 0.98) were associated with reduced odds of BC in adjusted models, while height was associated with non-statistically significant increased odds of BC (aOR: 1.07, 95% CI: 0.90, 1.28). In pre/peri-menopausal, but not post-menopausal women, both higher BMI and weight were significantly associated with reduced odds of BC. Further, higher BMI was associated with reduced odds of Luminal A, Luminal B, and HER2-enriched BC among pre/peri-menopausal women, and reduced odds of triple-negative BC among post-menopausal women. CONCLUSIONS: Higher BMI and weight were associated with reduced odds of BC overall and by molecular subtype among West African women. Larger studies of women of African descent are needed to definitively characterize these associations and inform cancer prevention strategies

Association of body composition with odds of breast cancer by molecular subtype: analysis of the Mechanisms for Established and Novel Risk Factors for Breast Cancer in Nigerian Women (MEND) study

Background: The association between obesity and breast cancer (BC) has been extensively studied among US, European and Asian study populations, with often conflicting evidence. However, despite the increasing prevalence of obesity and associated conditions in Africa, the continent with the highest age-standardized BC mortality rate globally, few studies have evaluated this association, and none has examined in relation to molecular subtypes among African women. The current analysis examines the association between body composition, defined by body mass index (BMI), height, and weight, and BC by molecular subtype among African women. Methods: We estimated odds ratios (ORs) and 95% confidence intervals (95% CI) for the association between measures of body composition and BC and molecular subtypes among 419 histologically confirmed cases of BC and 286 healthy controls from the Mechanisms for Established and Novel Risk Factors for Breast Cancer in Women of Nigerian Descent (MEND) case-control study. Results: Higher BMI (aOR: 0.79; 95% CI: 0.67, 0.95) and weight (aOR: 0.83; 95% CI: 0.69, 0.98) were associated with reduced odds of BC in adjusted models, while height was associated with non-statistically significant increased odds of BC (aOR: 1.07, 95% CI: 0.90, 1.28). In pre/peri-menopausal, but not post-menopausal women, both higher BMI and weight were significantly associated with reduced odds of BC. Further, higher BMI was associated with reduced odds of Luminal A, Luminal B, and HER2-enriched BC among pre/peri-menopausal women, and reduced odds of triple-negative BC among post-menopausal women. Conclusions: Higher BMI and weight were associated with reduced odds of BC overall and by molecular subtype among West African women. Larger studies of women of African descent are needed to definitively characterize these associations and inform cancer prevention strategies

Association of lipid profile biomarkers with breast cancer by molecular subtype: analysis of the MEND study

There is conflicting evidence on the role of lipid biomarkers in breast cancer (BC), and no study to our knowledge has examined this association among African women. We estimated odds ratios (ORs) and 95% confidence intervals (95% CI) for the association of lipid biomarkers—total cholesterol, high-density lipoprotein (HDL), low-density lipoprotein (LDL), and triglycerides—with odds of BC overall and by subtype (Luminal A, Luminal B, HER2-enriched and triple-negative or TNBC) for 296 newly diagnosed BC cases and 116 healthy controls in Nigeria. Each unit standard deviation (SD) increase in triglycerides was associated with 39% increased odds of BC in fully adjusted models (aOR: 1.39; 95% CI: 1.03, 1.86). Among post-menopausal women, higher total cholesterol (aOR: 1.65; 95% CI: 1.06, 2.57), LDL cholesterol (aOR: 1.59; 95% CI: 1.04, 2.41), and triglycerides (aOR: 1.91; 95% CI: 1.21, 3.01) were associated with increased odds of BC. Additionally, each unit SD increase in LDL was associated with 64% increased odds of Luminal B BC (aOR 1.64; 95% CI: 1.06, 2.55). Clinically low HDL was associated with 2.7 times increased odds of TNBC (aOR 2.67; 95% CI: 1.10, 6.49). Among post-menopausal women, higher LDL cholesterol and triglycerides were significantly associated with increased odds of Luminal B BC and HER2 BC, respectively. In conclusion, low HDL and high LDL are associated with increased odds of TN and Luminal B BC, respectively, among African women. Future prospective studies can definitively characterize this association and inform clinical approaches targeting HDL as a BC prevention strategy

Distribution and characteristics of endometriotic lesions in south- western Nigeria: a single institutional experience

Background: Endometriosis poses a significant burden mainly to women of child bearing age. Historically, endometriosis was thought to be of low prevalence among African women. However, recent studies have documented an increased prevalence than previously thought. This study aimed to determine the distribution and characteristics of endometriotic lesions among Nigerian women.Methods: A retrospective study of all histologically diagnosed cases of endometriosis from the records of the Department of Pathology, University College Hospital, Ibadan from 1st January, 1997 to 31st October, 2018.The age of the women, location and distribution of the lesions were analysed.Results: A total of 85 cases of endometriosis were diagnosed histologically in the period under review. The mean age was 35 years with an age range of 18 to 52 years. The most commonly affected age groups were those between 30-39 years (47.1%) and 20-29 years (30.6%). The most commonly affected site was the ovary (58.8%) followed by the umbilicus (11.9%) and fallopian tubes (9.4%). Fourteen patients (28%) had bilateral ovarian involvement. Left sided ovarian lesions predominated (61.1% versus 38.9%). Eighteen (21.2%) patients had lesions at more than one site frequently involving both ovaries.Conclusion: Endometriosis affected mainly women of childbearing age with particular predilection for the ovaries. Endometriosis affecting the umbilicus is not uncommon among Nigerian women.Keywords: Endometriosis, Ibadan, Nigeria, ovary, umbilicu

Nasopharyngeal carcinoma in Ibadan, Nigeria: a clinicopathologic study

Introduction: nasopharyngeal carcinoma is relatively common in our environment. It is one of the most difficult malignancies to diagnose at an early stage. The aim of the study was to determine the clinical features, clinical disease stage of nasopharyngeal carcinoma at presentation and at diagnosis as well as the histologic types at the University College Hospital, Ibadan, Nigeria. Methods: this was a ten year retrospective study of all histologically confirmed nasopharyngeal carcinoma between January 2007 to December 2016 using clinical and pathology records and files. Results: there were 73 cases. The male: female ratio was 1.7. The age of patients ranged from 12 to 80 years with a mean age of 39 ± 16 years. The median age at diagnosis was 40 years. The peak age group of occurrence was 40-49 years. The most common symptoms were namely epistaxis in 67.1% of patients at presentation, neck mass/swelling (64.4%) and nasal mass/obstruction (63.0%). Majority (54.8%) of the patients presented late with stage 3 or 4 disease. Most (94.5%) of the tumours were of the non-keratinizing squamous cell carcinoma subtype. The keratinizing and basaloid variants accounted for 4.1% and 1.4% of the tumours respectively. Conclusion: vague, non-specific symptoms make patients present at late stages of the disease, making it almost impossible to attempt cure. The dominant histopathological type is non-keratinizing squamous cell carcinoma and resembles that seen in most parts of Nigeria and endemic areas of the world