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.

The importance of the autopsy in ascertaining the cause of death and as an audit tool at the university college hospital, Ibadan.

BACKGROUND: Different reasons for autopsies include medico-legal causes, medical education and deducing the cause of death. An additional benefit is auditing with regards to patient care in the diagnosis and treatment of diseases. The main objective of this study was to determine the concordance between ante-mortem clinical diagnoses and post-mortem causes of death. MATERIALS AND METHODS: From January 2009 to December 2015, Autopsy records at the Department of Pathology, University College Hospital, Ibadan were reviewed. Discrepancies between the clinical diagnoses and postmortem findings were categorised using Goldman criteria into major and minor classes. Goldman's criteria can be sub-categorised into five classes: Class I, Class II, Class III, Class IV and Class V. Classification of the cause of death categories was by the International Classification of Diseases, Version 10. The study was carried out with respect to the world medical association's Declaration of Helsinki (2013). Data analysis was carried out with the use of the Statistical Package for the Social Sciences (SPSS version 22). RESULTS: Five hundred and thirty-three cases were involved with a male-female ratio of 1.6. The most common postmortem causes of death were traumatic Injuries (20.6%), Circulatory system-related deaths (19.7%), infections (16.9%) and malignant neoplasms (9.4%). Only 298 (55.9%) of the cases showed a concordance between the post-mortem causes of death and the clinical diagnosis. CONCLUSION: The post-mortem autopsy is useful in the audit of current medical practice in our environment.

Metabolic Syndrome and Risk of Breast Cancer by Molecular Subtype: Analysis of the MEND Study.

BACKGROUND: Metabolic syndrome (MetS) is characterized by a cluster of biological irregularities. The purpose of this analysis was to examine the association of MetS with BC among Nigerian women, and for the first time evaluate this association by molecular subtype. MATERIALS AND METHODS: MetS was defined as having at least 3 out of 5 of: high blood pressure (≥ 130/85 mm Hg), reduced HDL (< 50 mg/dL), elevated triglyceride (> 150 mg/dL), high waist circumference (≥ 80 cm), and prior diagnosis of diabetes or elevated fasting glucose level (≥ 100 mg/dL). Among 296 newly diagnosed BC cases and 259 healthy controls, multivariable logistic regression models were utilized to estimate adjusted odds ratios (aOR) and 95% confidence intervals (95% CI) for the association between MetS and BC overall. Multinomial logistic regression models were used to evaluate each molecular subtype (Luminal A, Luminal B, HER2-enriched and triple-negative or TNBC). RESULTS: After adjusting for age, socio-demographic and reproductive risk factors, there was a positive association between MetS and BC (aOR: 1.84, 95% CI: 1.07, 3.16). In stratified analyses, MetS was associated with BC regardless of BMI status; however, the estimate was significant only among normal weight women (aOR: 3.85; 95% CI: 1.25, 11.90). MetS was significantly associated with TNBC subtype (aOR: 4.37, 95% CI: 1.67, 11.44); associations for other molecular subtypes were not statistically significant. CONCLUSION: MetS appears to be a robust risk factor for BC, particularly for TNBC. Public health and clinical interventions can provide substantial benefits in reducing the burden of MetS and preventing BC among Nigerian women.

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 Life-Course Educational Attainment and Breast Cancer Grade in the MEND Study.

Background: Nigeria reports the highest age-standardized mortality rate for breast cancer (BC) among African countries and disproportionately high rates of high-grade cancer. Histological grade is a strong predictor of mortality, and evidence suggests that educational attainment influences cancer outcomes. Objective: We characterize the association between educational trends across the life-course and BC grade at diagnosis. Methods: Data on 224 BC patients enrolled in the Mechanisms for Established and Novel Risk Factors for Breast Cancer in Nigerian Women (MEND) study was analyzed. Participant and parental (mother and father) education was categorized as low (primary school or less) or high (secondary school or greater). Accordingly, the educational trend across the life-course was determined for each participant relative to each parent: stable high, increasing, decreasing, or stable low. BC grade was classified as high (grade 3) or low (grades 1-2). Findings: About 34% of participants, 71% of fathers, and 85% of mothers had low education. Approximately one-third of participants were diagnosed with high-grade BC. Participants with low-grade BC were more likely to have highly educated fathers (p = 0.04). After adjusting for age, comorbidities, marital status and mammogram screening, participants with highly educated fathers were 60% less likely to have high-grade BC (aOR 0.41; 95% CI 0.20 to 0.84) compared to those with less-educated fathers. Stable high life-course education relative to father was also associated with a significantly lower likelihood of having high-grade BC (aOR 0.36; 95% CI 0.15 to 0.87) compared to stable low life-course education. No significant associations were observed for the participant's education, mother's education, or life-course education relative to mother. Conclusions: Early-life socioeconomic status (SES) may influence BC grade. This deserves further study to inform policies that may be useful in reducing high-grade BC in Nigeria.

Association of high-sensitivity C-reactive protein and odds of breast cancer by molecular subtype: analysis of the MEND study.

Breast cancer (BC) in Nigeria is characterized by disproportionately aggressive molecular subtypes. C-reactive protein (CRP) is associated with risk and aggressiveness for several types of cancer. We examined the association of high-sensitivity CRP (hsCRP) with odds of BC by molecular subtype among Nigerian women. Among 296 newly diagnosed BC cases and 259 healthy controls, multivariable logistic regression models were used to estimate adjusted odds ratios (aOR) and 95% confidence intervals (CI) for the association between hsCRP and odds of BC overall and by molecular subtype (luminal A, luminal B, HER2-enriched and triple-negative or TNBC). High hsCRP (> 3 mg/L) was observed in 57% of cases and 31% of controls and was associated with 4 times the odds of BC (aOR: 4.43; 95% CI: 2.56, 7.66) after adjusting for socio-demographic, reproductive, and clinical variables. This association persisted regardless of menopausal status and body mass index (BMI) category. High hsCRP was associated with increased odds of TNBC (aOR: 3.32; 95% CI: 1.07, 10.35), luminal A BC (aOR: 4.03; 95% CI: 1.29, 12.64), and HER2-enriched BC (aOR: 6.27; 95% CI: 1.69, 23.25). Future studies are necessary in this population to further evaluate a potential role for CRP as a predictive biomarker for BC.

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.

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.