Novel breast cancer susceptibility loci under linkage peaks identified in African ancestry consortia.

BACKGROUND: Expansion of genome-wide association studies across population groups is needed to improve our understanding of shared and unique genetic contributions to breast cancer. We performed association and replication studies guided by a priori linkage findings from African ancestry (AA) relative pairs. METHODS: We performed fixed-effect inverse-variance weighted meta-analysis under three significant AA breast cancer linkage peaks (3q26-27, 12q22-23, and 16q21-22) in 9241 AA cases and 10 193 AA controls. We examined associations with overall breast cancer as well as estrogen receptor (ER)-positive and negative subtypes (193,132 SNPs). We replicated associations in the African-ancestry Breast Cancer Genetic Consortium (AABCG). RESULTS: In AA women, we identified two associations on chr12q for overall breast cancer (rs1420647, OR = 1.15, p = 2.50×10-6; rs12322371, OR = 1.14, p = 3.15×10-6), and one for ER-negative breast cancer (rs77006600, OR = 1.67, p = 3.51×10-6). On chr3, we identified two associations with ER-negative disease (rs184090918, OR = 3.70, p = 1.23×10-5; rs76959804, OR = 3.57, p = 1.77×10-5) and on chr16q we identified an association with ER-negative disease (rs34147411, OR = 1.62, p = 8.82×10-6). In the replication study, the chr3 associations were significant and effect sizes were larger (rs184090918, OR: 6.66, 95% CI: 1.43, 31.01; rs76959804, OR: 5.24, 95% CI: 1.70, 16.16). CONCLUSION: The two chr3 SNPs are upstream to open chromatin ENSR00000710716, a regulatory feature that is actively regulated in mammary tissues, providing evidence that variants in this chr3 region may have a regulatory role in our target organ. Our study provides support for breast cancer variant discovery using prioritization based on linkage evidence.

Unawareness of breast cancer family history among African women.

Introduction: comprehensive cancer risk assessment services are lacking in most sub-Saharan African countries and the use of accurate family history (FH) information could serve as a cheap strategy for risk evaluation. The aim of this study is to determine the proportion of women unaware of family history of cancer among female relatives and associated socio-demographic characteristics. Methods: using case-control data on breast cancer among 4294 women in Nigeria, Uganda and Cameroon, we investigated the proportion of women unaware of family history of cancer among their female relatives. The association between participants' response to their awareness of female relatives' cancer history and socio-demographic characteristics was analysed according to case-control status, family side and distance of relation. Results: the proportion of women unaware if any relative had cancer was 33%, and was significantly higher among controls (43.2%) compared to 23.9% among cases (p<0.001) (Adjusted Odds Ratio (OR) = 2.51, 95% CI = 2.14 - 2.95). Age, education and marital status remained significantly associated with being unaware of FH among controls on multiple regression. Conclusion: about a third of women interviewed did not know about cancer history in at least one of their female relatives. Efforts aimed at improving cancer awareness in sub-Saharan Africa (SSA) are needed. Our findings could be useful for future studies of cancer risk assessment in SSA.

Cancer Genetic Services in a Low- to Middle-Income Country: Cross-Sectional Survey Assessing Willingness to Undergo and Pay for Germline Genetic Testing.

PURPOSE: Cancer genetic testing (CGT), a pathway to personalized medicine, is also being embraced in Nigeria. However, little is known about the influence of demographics and perceptions on individuals' willingness to access and pay for CGT. This study assessed patients' willingness to undergo CGT in southwest Nigeria as a catalyst for sustainable Cancer Risk Management Program. METHODS: This was a cross-sectional study using semistructured questionnaire to interview 362 patients with cancer and 10 referred first-degree relatives between July 2018 and February 2020. Participants from three Nigerian teaching hospitals-University College Hospital, Ibadan, Lagos State University Teaching Hospital, Lagos, and Lagos University Teaching Hospital, Lagos, received genetic counseling and had subsequent CGT. Primary outcomes were willingness to undergo CGT in determining cancer risk and the willingness to pay for it. Ethical approval was from appropriate ethics committees of participating hospitals. Data were analyzed with SPSS version 22. Univariate comparison of categorical variables was performed by χ2 test, multivariate analysis by logistic regression. RESULTS: The participants from University College Hospital (56.2%), Lagos State University Teaching Hospital (26.3%), and Lagos University Teaching Hospital (17.5%) were mostly female (98.4%). Mean age was 48.8 years ± 11.79. Three hundred twenty-two (86.6%) patients and first-degree relatives were willing to take the test, of whom 231 (71.1%) were willing to pay for it. more than half (53.6%) of the participants were willing to pay between N10,000 and N30,000, which is less than $100 US dollars. Sociodemographic variables and willingness to test showed no association (P > .05). Education and ethnicity were found to be associated with their willingness to pay for CGT (P ≤ .05). CONCLUSION: Learning clinically relevant details toward cancer prevention informs health-related decisions in patients and relatives, a motivator for willingness to pay for genetic testing in low- and middle-income countries. Increased awareness may influence outcomes of cancer risk management.

Polygenic risk scores for prediction of breast cancer risk in women of African ancestry: a cross-ancestry approach.

Polygenic risk scores (PRSs) are useful for predicting breast cancer risk, but the prediction accuracy of existing PRSs in women of African ancestry (AA) remains relatively low. We aim to develop optimal PRSs for the prediction of overall and estrogen receptor (ER) subtype-specific breast cancer risk in AA women. The AA dataset comprised 9235 cases and 10 184 controls from four genome-wide association study (GWAS) consortia and a GWAS study in Ghana. We randomly divided samples into training and validation sets. We built PRSs using individual-level AA data by a forward stepwise logistic regression and then developed joint PRSs that combined (1) the PRSs built in the AA training dataset and (2) a 313-variant PRS previously developed in women of European ancestry. PRSs were evaluated in the AA validation set. For overall breast cancer, the odds ratio per standard deviation of the joint PRS in the validation set was 1.34 [95% confidence interval (CI): 1.27-1.42] with the area under receiver operating characteristic curve (AUC) of 0.581. Compared with women with average risk (40th-60th PRS percentile), women in the top decile of the PRS had a 1.98-fold increased risk (95% CI: 1.63-2.39). For PRSs of ER-positive and ER-negative breast cancer, the AUCs were 0.608 and 0.576, respectively. Compared with existing methods, the proposed joint PRSs can improve prediction of breast cancer risk in AA women.

Oncology Training Needs Assessment Among Health Care Professionals in Nigeria.

PURPOSE: This study investigated the status of training and preparedness for oncology practice and research and degree of interprofessional collaboration among health care professionals in the six geopolitical regions of Nigeria. METHODS: A convergent parallel mixed methods design was used. Three hundred seventeen respondents completed a three-part, online questionnaire. Self-rated competencies in oncology research (26 items), oncology practice (16 items), and interprofessional collaboration (nine items) were assessed with a one- to five-point Likert scale. Six key informant and 24 in-depth interviews were conducted. Descriptive statistics, analysis of variance, and pairwise t-test were used to analyze the quantitative data, whereas thematic analysis was used for the qualitative data. RESULTS: Respondents were mostly female (65.6%) with a mean age of 40.5 ± 8.3 years. Respondents include 178 nurses (56.2%), 93 medical doctors (29.3%), and 46 pharmacists (14.5%). Self-assessed competencies in oncology practice differed significantly across the three groups of health care professionals (F = 4.789, P = .009). However, there was no significant difference across professions for competency in oncology research (F = 1.256, P = .286) and interprofessional collaboration (F = 1.120, P = .327). The majority of respondents (267, 82.4%) felt that educational opportunities in oncology-associated research in the country are inadequate and that this has implications for practice. Key training gaps reported include poor preparedness in data analysis and bioinformatics (138, 43.5%), writing clinical trials (119, 37.5%), and writing grant/research proposals (105, 33.1%). Challenges contributing to gaps in cancer research include few trained oncology specialists, low funding for research, and inadequate interprofessional collaboration. CONCLUSION: This study highlights gaps in oncology training and practice and an urgent need for interventions to enhance interprofessional training to improve quality of cancer care in Nigeria. These would accelerate progress toward strengthening the health care system and reducing global disparities in cancer outcomes.

Exposure to oil pollution and maternal outcomes: The Niger Delta prospective cohort study.

BACKGROUND: Maternal exposure to oil pollution is an important public health concern. However, there is a dearth of literature on the effects of maternal exposure to oil pollution on maternal outcomes in the Niger Delta region of Nigeria. This study was therefore designed to determine the effect of maternal exposure to oil pollution on maternal outcomes in the Niger Delta region of Nigeria. METHODS: Prospective cohort study design involving 1720 pregnant women followed from pregnancy to delivery was conducted. The participants were 18-45 years old at a gestational age of less than 17 weeks, who attended randomly selected health facilities in the areas with high exposure and low exposure to oil pollution in the Niger Delta, Nigeria. Data were collected using an interviewer-administered questionnaire and review of medical records from April 2018 to April 2019. Multivariate log-binomial model was used to examine the effect of maternal exposure to oil pollution on the risk of adverse maternal outcomes adjusting for sociodemographic, maternal and lifestyle characteristics. RESULTS: A total of 1418 women completed the follow-up and were included in the analysis. Women in high exposure areas had a higher incidence of premature rupture of membrane (PROM), caesarean section (CS) and postpartum haemorrhage (PPH) compared to women in areas with low exposure to oil pollution. After adjusting for cofounders, women in high exposure areas also had a higher risk of PROM (ARR = 1.96; 95% CI: 1.24-3.10) and PPH (ARR = 2.12; 95% CI: 1.28-3.36) in Model I-III when compared to women in areas with low exposure to oil pollution. However, pregnancy-induced hypertension and CS had no association with maternal exposure area status to oil pollution. CONCLUSION: Women in high exposure areas are at a higher risk of PROM and PPH. This calls for policies and intervention toward reducing maternal exposure to oil pollution in the Niger Delta region of Nigeria.

Outcomes of surgical treatments for acquired gynatresia in a tertiary institution in Ibadan, Nigeria.

A 16-year review of causes, clinical presentation and management outcomes of Acquired gynatresia (AG) at University College Hospital, Ibadan, Nigeria. Information was obtained using a proforma and data analysed using SPSS version 20.0. The mean age of the 31 women with AG was 35.6 ± 6.2 years. The majority (90.3%) were married and had a tertiary level of education. The mean parity was 0.74 ± 1.1 and 54.8% were nulliparous while 29.0% were primiparous women. The commonest cause of AG was the insertion of caustic substances into the vagina and this was mainly for the treatment of uterine fibroid (68.2%) and infertility (54.5%). Over three-quarters presented with dyspareunia while 54.8% had infertility. A majority (87.1%) had one-stage surgery with dissection/excision of fibrotic tissue being the commonest (45.2%) and sigmoid vaginoplasty the least performed. Postoperative complications were seen in 29.0% of cases. Acquired gynatresia remains a condition of public health interest despite an increase in female education and relatively improved health care in Nigeria.Impact statementWhat is already known on this subject? Acquired gynatresia (AG) could be of chemical and non-chemical origin and result from certain cultural beliefs and practices.What do the results of this study add? Irrespective of the women's level of education, there is inadequate awareness of the implications of inserting caustic materials into the vagina. However, there is a high success rate of treatment of AG.What the implications are of these findings for clinical practice and/or further research? There is a need to increase health education and awareness of the populace on the causes of AG and its associated complications.

Whole-genome analysis of Nigerian patients with breast cancer reveals ethnic-driven somatic evolution and distinct genomic subtypes.

Black women across the African diaspora experience more aggressive breast cancer with higher mortality rates than white women of European ancestry. Although inter-ethnic germline variation is known, differential somatic evolution has not been investigated in detail. Analysis of deep whole genomes of 97 breast cancers, with RNA-seq in a subset, from women in Nigeria in comparison with The Cancer Genome Atlas (n = 76) reveal a higher rate of genomic instability and increased intra-tumoral heterogeneity as well as a unique genomic subtype defined by early clonal GATA3 mutations with a 10.5-year younger age at diagnosis. We also find non-coding mutations in bona fide drivers (ZNF217 and SYPL1) and a previously unreported INDEL signature strongly associated with African ancestry proportion, underscoring the need to expand inclusion of diverse populations in biomedical research. Finally, we demonstrate that characterizing tumors for homologous recombination deficiency has significant clinical relevance in stratifying patients for potentially life-saving therapies.

Intimate partner violence among pregnant women attending antenatal care services in the rural Gambia.

BACKGROUND: Intimate partner violence (IPV) refers to any behavior by either a current or ex-intimate partner or would-be rejected lover that causes physical, sexual, or psychological harm. It is the most common form of violence in women's lives. According to a World Health Organization report, about 1 in 3 women worldwide experience at least one form of IPV from an intimate partner at some point in her life. In the Gambia, about 62% of pregnant women experience at least one form of violence from an intimate partner. IPV has severe physical and mental health consequences on a woman ranging from minor bodily injury to death. It also increases the risk of low birth weight, premature delivery, and neonatal death. METHODS: A health facility-based cross-sectional study design was carried out to assess the magnitude and factors associated with intimate partner violence among pregnant women seeking antenatal care in the rural Gambia. The study enrolled 373 pregnant women, and a multi-stage sampling technique was used to select the respondents. An interviewer-administered structured questionnaire was used to obtain information from the study participants. The collected data were analyzed using SPSS Ver.22. Bivariate and multivariate logistic regression were used to determine the association between dependent and independent variables. Odds ratio with 95% confidence interval (CI) was computed to determine the presence and strength of associated factors with IPV. RESULT: The study reveals that the prevalence of IPV in The Gambia is 67%, with psychological violence (43%) being the most common form of IPV reported by the respondents. The multivariate logistic regression result reveals that being aged 35 years or older [AOR 5.1(95% CI 1.5-17.8)], the experience of parents quarreling during childhood [AOR 1.7(95% CI 1.0-2.75)], and having cigarette smoking partners [AOR 2.3 (95% CI 1.10-4.6)] were significantly associated with IPV during pregnancy. CONCLUSION: This study has demonstrated that all forms of IPV in rural Gambia are frequent. Women older than 35 years, had experienced parents quarreling, had a partner who smoked, and a partner who fight with others were more likely report IPV compared to other pregnant women in the study. We recommend that IPV screening should be included as an integral part of routine antenatal care services in The Gambia. Community-based interventions that include indigenous leaders, religious leaders, and other key stakeholders are crucial to create awareness on all forms of IPV and address the risk factors found to influence the occurrence of IPV in rural Gambia.

Cross-ancestry GWAS meta-analysis identifies six breast cancer loci in African and European ancestry women.

Our study describes breast cancer risk loci using a cross-ancestry GWAS approach. We first identify variants that are associated with breast cancer at P < 0.05 from African ancestry GWAS meta-analysis (9241 cases and 10193 controls), then meta-analyze with European ancestry GWAS data (122977 cases and 105974 controls) from the Breast Cancer Association Consortium. The approach identifies four loci for overall breast cancer risk [1p13.3, 5q31.1, 15q24 (two independent signals), and 15q26.3] and two loci for estrogen receptor-negative disease (1q41 and 7q11.23) at genome-wide significance. Four of the index single nucleotide polymorphisms (SNPs) lie within introns of genes (KCNK2, C5orf56, SCAMP2, and SIN3A) and the other index SNPs are located close to GSTM4, AMPD2, CASTOR2, and RP11-168G16.2. Here we present risk loci with consistent direction of associations in African and European descendants. The study suggests that replication across multiple ancestry populations can help improve the understanding of breast cancer genetics and identify causal variants.

Implementing oncology clinical trials in Nigeria: a model for capacity building.

BACKGROUND: There is both higher mortality and morbidity from cancer in low and medium income countries (LMICs) compared with high income countries (HICs). Clinical trial activities and development of more effective and less toxic therapies have led to significant improvements in morbidity and mortality from cancer in HICs. Unfortunately, clinical trials remain low in LMICs due to poor infrastructure and paucity of experienced personnel to execute clinical trials. There is an urgent need to build local capacity for evidence-based treatment for cancer patients in LMICs. METHODS: We conducted a survey at facilities in four Teaching Hospitals in South West Nigeria using a checklist of information on various aspects of clinical trial activities. The gaps identified were addressed using resources sourced in partnership with investigators at HIC institutions. RESULTS: Deficits in infrastructure were in areas of patient care such as availability of oncology pharmacists, standard laboratories and diagnostic facilities, clinical equipment maintenance and regular calibrations, trained personnel for clinical trial activities, investigational products handling and disposals and lack of standard operating procedures for clinical activities. There were two GCP trained personnel, two study coordinators and one research pharmacist across the four sites. Interventions were instituted to address the observed deficits in all four sites which are now well positioned to undertake clinical trials in oncology. Training on all aspects of clinical trial was also provided. CONCLUSIONS: Partnerships with institutions in HICs can successfully identify, address, and improve deficits in infrastructure for clinical trial in LMICs. The HICs should lead in providing funds, mentorship, and training for LMIC institutions to improve and expand clinical trials in LMIC countries.

Miscarriage, stillbirth, and infant death in an oil-polluted region of the Niger Delta, Nigeria: A retrospective cohort study.

OBJECTIVE: To determine the association between oil pollution and miscarriage, stillbirth, and infant death in the Niger Delta region of Nigeria. METHODS: A retrospective cohort study was undertaken of pregnant women (aged 18-45 years) who attended selected health facilities in regions with high and low exposure to oil pollution from May 14, 2018, to September 27, 2018. A multistage sampling technique was used to randomly select a representative of women with high and low exposure to oil pollution. An interviewer-administered questionnaire was used for data collection. Bivariate and multivariable logistic regression analyses were employed to adjust for confounding factors of miscarriage, stillbirth, and infant death. RESULTS: In total, 1564 pregnant women were included in the study. Women with high exposure to oil pollution were more likely to experience stillbirth (odds ratio [OR] 1.806; 95% confidence interval [CI] 1.177-2.770) and infant death (OR 2.162; 95% CI 1.409-3.317). However, after adjusting for potential confounders, only infant death was associated with high exposure (adjusted OR 1.843; 95% CI 1.146-2.962). No association was found between miscarriage and high exposure to oil pollution. CONCLUSION: Women with high exposure to oil pollution are at higher risk of infant death.

Perception Determinants of Women and Healthcare Providers on the Effects of Oil Pollution on Maternal and Newborn Outcomes in the Niger Delta, Nigeria.

PURPOSE: This qualitative study examined the perception determinants of women and their local healthcare providers on exposure to oil pollution and its adverse effects on maternal and newborn outcomes in selected communities with history of oil spillage and gas flaring in the Niger Delta region of Nigeria. PARTICIPANTS AND METHODS: Thirty-nine participants were used in this study, which included community women leaders (n=2), women of reproductive ages (n=32) and healthcare providers (n= 3 female nurses and 2 male doctors) in the selected communities in the Niger Delta region of Nigeria. The participants were chosen through purposive sampling. Focus group discussions (FGDs) and in-depth interviews (IDIs) were conducted among the participants and recorded in line with research protocols. The recordings of the FGDs and IDIs were transcribed, coded and analysed using Nvivo 10. RESULTS: Four major themes emerged relating to the perception determinants of women and healthcare workers on the effects of oil pollution on maternal and newborn outcomes. The first theme relates to the fact that personal experiences influence risk perception. The second theme associated perception with cultural norms, values and practices. The third theme shows that perception is influenced by the level of environmental threat or hazard, while the fourth theme borders around the influence of hospital-related factors on risk perception. CONCLUSION: The study strongly suggested that both women and local healthcare providers perceived that oil pollution could have adverse effects on maternal and newborn outcomes. However, their perceptions were influenced by the cultural beliefs of the people, individual experiences, environmental and hospital-related factors. We believe that increasing awareness on the importance of attending antenatal care during pregnancy, making hospital charges affordable for pregnant women, and general environment conduciveness will improve maternal and newborn health in communities affected by oil pollution in the Niger Delta region.

Breast Cancer Knowledge Assessment of Health Workers in Ibadan, Southwest Nigeria.

PURPOSE: Breast cancer is the most common cancer among women, and in low- to middle-income countries late-stage diagnosis contributes to significant mortality. Previous research at the University College Hospital, a tertiary hospital in Ibadan, Nigeria, on social factors contributing to late diagnosis revealed that many patients received inappropriate initial treatment. METHODS: The level of breast cancer knowledge among health practitioners at various levels of the health system was assessed. We developed a tool tailored to local needs to assess knowledge of symptoms, risk factors, treatments, and cultural beliefs. The recruitment included doctors, nurses, and pharmacists in public hospitals, physicians and pharmacists in private practice, nurses and health care workers from primary health care centers, community birth attendants, and students in a health care field from state schools. RESULTS: A total of 1,061 questionnaires were distributed, and 725 providers responded (68%). Seventy-eight percent were female, and > 90% were Yoruba, the dominant local ethnic group. The majority were Christian, and 18% were Muslim. Median knowledge score was 31 out of 56, and the differences in scores between health care worker types were statistically significant (P < .001). Nearly 60% of the participants believed breast cancer is always deadly. More than 40% of participants believed that keeping money in the bra causes breast cancer, and approximately 10% believed that breast cancer is caused by a spiritual attack. CONCLUSION: Our questionnaire revealed that, even at the tertiary care level, significant gaps in knowledge exist, and knowledge of breast cancer is unacceptably low at the level of community providers. In addition to efforts aimed at strengthening health systems, greater knowledge among community health care workers has the potential to reduce delays in diagnosis for Nigerian patients with breast cancer.

Germline variants and somatic mutation signatures of breast cancer across populations of African and European ancestry in the US and Nigeria.

Somatic mutation signatures may represent footprints of genetic and environmental exposures that cause different cancer. Few studies have comprehensively examined their association with germline variants, and none in an indigenous African population. SomaticSignatures was employed to extract mutation signatures based on whole-genome or whole-exome sequencing data from female patients with breast cancer (TCGA, training set, n = 1,011; Nigerian samples, validation set, n = 170), and to estimate contributions of signatures in each sample. Association between somatic signatures and common single nucleotide polymorphisms (SNPs) or rare deleterious variants were examined using linear regression. Nine stable signatures were inferred, and four signatures (APOBEC C>T, APOBEC C>G, aging and homologous recombination deficiency) were highly similar to known COSMIC signatures and explained the majority (60-85%) of signature contributions. There were significant heritable components associated with APOBEC C>T signature (h2 = 0.575, p = 0.010) and the combined APOBEC signatures (h2 = 0.432, p = 0.042). In TCGA dataset, seven common SNPs within or near GNB5 were significantly associated with an increased proportion (beta = 0.33, 95% CI = 0.21-0.45) of APOBEC signature contribution at genome-wide significance, while rare germline mutations in MTCL1 was also significantly associated with a higher contribution of this signature (p = 6.1 × 10-6 ). This is the first study to identify associations between germline variants and mutational patterns in breast cancer across diverse populations and geography. The findings provide evidence to substantiate causal links between germline genetic risk variants and carcinogenesis.

Our Experience with Iatrogenic Ureteric Injuries among Women Presenting to University College Hospital, Ibadan: A Call to Action on Trigger Factors.

BACKGROUND: Ureteric injuries leading to ureterovaginal fistula (UVF) is less common than vesicovaginal fistula, as a cause of urinary incontinence. Recently, there is a surge in the number of UVF cases presenting to University College Hospital (UCH) following a caesarean delivery. The urogynaecology unit at UCH is at the forefront of providing surgical repair for women with all forms of genitourinary fistulas. We describe our experience with managing UVF arising from ureteric injury. METHODS: A retrospective data collection of UVF cases managed from January 2012-December 2017 at UCH is presented. Information on sociodemographic and obstetric characteristics, presenting complaints, antecedent surgery, treatment received, findings at surgery, and postoperative complications were obtained with a structured proforma. RESULTS: Eighteen cases of UVFs due to iatrogenic ureteric injury were managed. Majority (N=11; 61.1%) of the women suffered the injury following the emergency caesarean section (EMCS). Abdominal hysterectomy operation accounted for four (22.2%) cases, and one case each (5.6%) was due to vaginal hysterectomy and destructive operations. Prolonged obstructed labour (POL) (81.8%) was the most common indication for the EMCS, while 18.2% had surgery on account of lower uterine segment fibroid. Most of the ureteric injuries were on the left side. Postoperative complications documented were haemorrhage, urinary tract infection, wound infection, and injury to the neighbouring structure. CONCLUSION: Caesarean section being one of the most performed surgical operations in Nigeria was surprisingly found to be the most common cause of ureteric injury ahead of hysterectomy. It is a pointer that the surgeons might not have properly learnt the art of the caesarean delivery well. We recommend adequate surgical training of medical officers/surgeons that are involved.

Author Correction: Characterization of Nigerian breast cancer reveals prevalent homologous recombination deficiency and aggressive molecular features.

The original version of this Article contained an error in the author affiliations. The affiliation of Kevin P. White with Tempus Labs, Inc. Chicago, IL, USA was inadvertently omitted. This has now been corrected in both the PDF and HTML versions of the Article.

Characterization of Nigerian breast cancer reveals prevalent homologous recombination deficiency and aggressive molecular features.

Racial/ethnic disparities in breast cancer mortality continue to widen but genomic studies rarely interrogate breast cancer in diverse populations. Through genome, exome, and RNA sequencing, we examined the molecular features of breast cancers using 194 patients from Nigeria and 1037 patients from The Cancer Genome Atlas (TCGA). Relative to Black and White cohorts in TCGA, Nigerian HR + /HER2 - tumors are characterized by increased homologous recombination deficiency signature, pervasive TP53 mutations, and greater structural variation-indicating aggressive biology. GATA3 mutations are also more frequent in Nigerians regardless of subtype. Higher proportions of APOBEC-mediated substitutions strongly associate with PIK3CA and CDH1 mutations, which are underrepresented in Nigerians and Blacks. PLK2, KDM6A, and B2M are also identified as previously unreported significantly mutated genes in breast cancer. This dataset provides novel insights into potential molecular mechanisms underlying outcome disparities and lay a foundation for deployment of precision therapeutics in underserved populations.

A longitudinal study of the prevalence and characteristics of breast disorders detected by clinical breast examination during pregnancy and six months postpartum in Ibadan, Southwestern Nigeria.

BACKGROUND: Breast disorders cause great anxiety for women especially when they occur in pregnancy because breast cancer is the most common cause of cancer related deaths in women. Majority of the disorders are Benign Breast Diseases (BBD) with various degrees of associated breast cancer risks. With increasing breast cancer awareness in Nigeria, we sought to determine the prevalence and characteristics of breast disorders among a cohort of pregnant women. METHODS: A longitudinal study of 1248 pregnant women recruited in their first trimester- till 26 weeks gestational age consecutively from selected antenatal clinics (ANCs), in Ibadan, Southwest Nigeria. A pretested interviewer- administered questionnaire was used to collect information at recruitment. Clinical Breast Examination (CBE) using MammaCare® technique was performed at recruitment and follow up visits at third trimester, six weeks postpartum and six months postpartum. Women with breast disorders were referred for Breast Ultrasound Scan (BUS) and those with Breast Imaging Reporting and Data System (BIRADS) ≥4 had ultrasound guided biopsy. Statistical analysis was performed using Stata version 14. RESULTS: Mean age of participants was 29.7 ± 5.2 years and mean gestational age at recruitment was 20.4 ± 4.4 weeks. Seventy-two participants (5.8%) had a past history of BBD and 345 (27.6%) were primigravidae. Overall, breast disorder was detected among 223 (17.9%) participants and 149 (11.9%) had it detected at baseline. Findings from the CBE showed that 208 (69.6%) of 299 breast disorders signs found were palpable lumps or thickenings in the breast, 28 (9.4%) were persistent pain, and 63 (21.1%) were abscesses, infection and mastitis. Twenty out of 127 (15.7%) participants who had BUS performed were classified as BIRADS ≥3. Lesions found by BUS were reactive lymph nodes (42.5%), prominent ducts (27.1%), fibroadenoma (9.6%), breast cysts (3.8%) and fibrocystic changes (2.5%). No malignant pathology was found on ultrasound guided biopsy. CONCLUSIONS: Breast lump is a major breast disorder among pregnant women attending antenatal clinics in Ibadan. Routine clinical breast examination and follow up of pregnant women found with breast disorders could facilitate early detection of pregnancy associated breast cancer in low resource settings.

Inherited Breast Cancer in Nigerian Women.

PURPOSE: Among Nigerian women, breast cancer is diagnosed at later stages, is more frequently triple-negative disease, and is far more frequently fatal than in Europe or the United States. We evaluated the contribution of an inherited predisposition to breast cancer in this population. PATIENTS AND METHODS: Cases were 1,136 women with invasive breast cancer (mean age at diagnosis, 47.5 ± 11.5 years) ascertained in Ibadan, Nigeria. Patients were selected regardless of age at diagnosis, family history, or prior genetic testing. Controls were 997 women without cancer (mean age at interview, 47.0 ± 12.4 years) from the same communities. BROCA panel sequencing was used to identify loss-of-function mutations in known and candidate breast cancer genes. RESULTS: Of 577 patients with information on tumor stage, 86.1% (497) were diagnosed at stage III (241) or IV (256). Of 290 patients with information on tumor hormone receptor status and human epidermal growth factor receptor 2, 45.9% (133) had triple-negative breast cancer. Among all cases, 14.7% (167 of 1,136) carried a loss-of-function mutation in a breast cancer gene: 7.0% in BRCA1, 4.1% in BRCA2, 1.0% in PALB2, 0.4% in TP53, and 2.1% in any of 10 other genes. Odds ratios were 23.4 (95% CI, 7.4 to 73.9) for BRCA1 and 10.3 (95% CI, 3.7 to 28.5) for BRCA2. Risks were also significantly associated with PALB2 (11 cases, zero controls; P = .002) and TP53 (five cases, zero controls; P = .036). Compared with other patients, BRCA1 mutation carriers were younger ( P < .001) and more likely to have triple-negative breast cancer ( P = .028). CONCLUSION: Among Nigerian women, one in eight cases of invasive breast cancer is a result of inherited mutations in BRCA1, BRCA2, PALB2, or TP53, and breast cancer risks associated with these genes are extremely high. Given limited resources, prevention and early detection services should be especially focused on these highest-risk women.