Publications by authors named "Temidayo Ogundiran"

62 Publications

Polygenic Risk Scores for Prediction of Breast Cancer Risk in Women of African Ancestry: a Cross-Ancestry Approach.

Hum Mol Genet 2022 May 12. Epub 2022 May 12.

Division of Epidemiology, Department of Medicine, Vanderbilt Epidemiology Center, Vanderbilt-Ingram Cancer Center, Vanderbilt University School of Medicine, Nashville, TN, USA.

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 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 odd ratio (OR) per standard deviation of the joint PRS in the validation set was 1.34 (95% CI: 1.27-1.42) with area under receiver operating characteristic curve (AUC) of 0.581. Compared to 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 to existing methods, the proposed joint PRSs can improve prediction of breast cancer risk in AA women.
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http://dx.doi.org/10.1093/hmg/ddac102DOI Listing
May 2022

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

Nat Commun 2021 11 26;12(1):6946. Epub 2021 Nov 26.

Center for Clinical Cancer Genetics and Global Health, Department of Medicine, The University of Chicago, Chicago, IL, 60637, USA.

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.
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http://dx.doi.org/10.1038/s41467-021-27079-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8626467PMC
November 2021

Feasibility of genetic testing for cancer risk assessment programme in Nigeria.

Ecancermedicalscience 2021 7;15:1283. Epub 2021 Sep 7.

Center for Clinical Cancer Genetics, University of Chicago, Chicago, IL, 60637, USA.

Background: A high frequency of BRCA mutations has been established in Nigerian breast cancer (BC) patients. Recently, patients' and first-degree relatives' interest have been raised on cancer genetic risk assessment through our awareness activities in Nigeria. This led to the emergence of nurse-led cancer genetic counselling (CGC) and testing aimed at providing standard-of-care for individuals at increased risk of hereditary breast and ovarian cancers.

Methods: In June 2018, CGC and testing of patients with BC and ovarian cancer (OC) commenced in collaboration with Color Genomics Inc. for a 30-panel gene testing. Previously trained nurses in CGC at the University College Hospital, Ibadan offered genetic counselling (GC) to willing patients with BC and gynaecological cancer in four out-patient oncology clinics and departments for the pilot study. Consultation consisted of CGC, patient's history, pedigree and sample collection for genetic testing (GT).

Results: Forty-seven patients - 40 with BC, five with OC and two with endometrial cancer received GC, and all chose to undergo GT. The average age at testing was 48.2 ± 12.1 years. Eight women reported a known family cancer history and there were more perceived benefits than barriers to GT with the patients experiencing the desire for none of their relative to have cancer. Results revealed no mutations in 27 (57.4%), 16 (4.0%) variants of unknown significance and 4 (8.5%) pathogenic mutations.

Conclusion: Personalised cancer care utilises GC and testing for cancer risk assessment towards prevention and early detection in high risk women. The study indicates the necessity of expanded cancer genetic services for integration into patient care and cancer prevention.
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http://dx.doi.org/10.3332/ecancer.2021.1283DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8580592PMC
September 2021

Associations between age of menarche and genetic variation in women of African descent: genome-wide association study and polygenic score analysis.

J Epidemiol Community Health 2022 04 27;76(4):411-417. Epub 2021 Oct 27.

Department of Public Health Sciences, University of Chicago, Chicago, Illinois, USA

Introduction: Many diseases of adulthood are associated with a woman's age at menarche. Genetic variation affects age at menarche, but it remains unclear whether in women of African ancestry the timing of menarche is regulated by genetic variants that were identified in predominantly European and East Asian populations.

Methods: We explored the genetic architecture of age at menarche in 3145 women of African ancestry who live in the USA, Barbados and Nigeria. We undertook a genome-wide association study, and evaluated the performance of previously identified variants.

Results: One variant was associated with age at menarche, a deletion at chromosome 2 (chr2:207216165) (p=1.14×10). 349 genotyped variants overlapped with these identified in populations of non-African ancestry; these replicated weakly, with 51.9% having concordant directions of effect. However, collectively, a polygenic score constructed of those previous variants was suggestively associated with age at menarche (beta=0.288 years; p=0.041). Further, this association was strong in women enrolled in the USA and Barbados (beta=0.445 years, p=0.008), but not in Nigerian women (beta=0.052 years; p=0.83).

Discussion: This study suggests that in women of African ancestry the genetic drivers of age at menarche may differ from those identified in populations of non-African ancestry, and that these differences are more pronounced in women living in Nigeria, although some associated trait loci may be shared across populations. This highlights the need for well-powered ancestry-specific genetic studies to fully characterise the genetic influences of age at menarche.
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http://dx.doi.org/10.1136/jech-2020-216000DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9011920PMC
April 2022

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

Nat Commun 2021 07 7;12(1):4198. Epub 2021 Jul 7.

Department of Epidemiology, Gillings School of Global Public Health, University of North Carolina, Chapel Hill, NC, USA.

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.
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http://dx.doi.org/10.1038/s41467-021-24327-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8263739PMC
July 2021

Evaluating Polygenic Risk Scores for Breast Cancer in Women of African Ancestry.

J Natl Cancer Inst 2021 09;113(9):1168-1176

Department of Oncology, Centre for Cancer Genetic Epidemiology, University of Cambridge, Cambridge, UK.

Background: Polygenic risk scores (PRSs) have been demonstrated to identify women of European, Asian, and Latino ancestry at elevated risk of developing breast cancer (BC). We evaluated the performance of existing PRSs trained in European ancestry populations among women of African ancestry.

Methods: We assembled genotype data for women of African ancestry, including 9241 case subjects and 10 193 control subjects. We evaluated associations of 179- and 313-variant PRSs with overall and subtype-specific BC risk. PRS discriminatory accuracy was assessed using area under the receiver operating characteristic curve. We also evaluated a recalibrated PRS, replacing the index variant with variants in each region that better captured risk in women of African ancestry and estimated lifetime absolute risk of BC in African Americans by PRS category.

Results: For overall BC, the odds ratio per SD of the 313-variant PRS (PRS313) was 1.27 (95% confidence interval [CI] = 1.23 to 1.31), with an area under the receiver operating characteristic curve of 0.571 (95% CI = 0.562 to 0.579). Compared with women with average risk (40th-60th PRS percentile), women in the top decile of PRS313 had a 1.54-fold increased risk (95% CI = 1.38-fold to 1.72-fold). By age 85 years, the absolute risk of overall BC was 19.6% for African American women in the top 1% of PRS313 and 6.7% for those in the lowest 1%. The recalibrated PRS did not improve BC risk prediction.

Conclusion: The PRSs stratify BC risk in women of African ancestry, with attenuated performance compared with that reported in European, Asian, and Latina populations. Future work is needed to improve BC risk stratification for women of African ancestry.
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http://dx.doi.org/10.1093/jnci/djab050DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8418423PMC
September 2021

Discovery and fine-mapping of height loci via high-density imputation of GWASs in individuals of African ancestry.

Am J Hum Genet 2021 04 12;108(4):564-582. Epub 2021 Mar 12.

The Charles R. Bronfman Institute for Personalized Medicine, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.

Although many loci have been associated with height in European ancestry populations, very few have been identified in African ancestry individuals. Furthermore, many of the known loci have yet to be generalized to and fine-mapped within a large-scale African ancestry sample. We performed sex-combined and sex-stratified meta-analyses in up to 52,764 individuals with height and genome-wide genotyping data from the African Ancestry Anthropometry Genetics Consortium (AAAGC). We additionally combined our African ancestry meta-analysis results with published European genome-wide association study (GWAS) data. In the African ancestry analyses, we identified three novel loci (SLC4A3, NCOA2, ECD/FAM149B1) in sex-combined results and two loci (CRB1, KLF6) in women only. In the African plus European sex-combined GWAS, we identified an additional three novel loci (RCCD1, G6PC3, CEP95) which were equally driven by AAAGC and European results. Among 39 genome-wide significant signals at known loci, conditioning index SNPs from European studies identified 20 secondary signals. Two of the 20 new secondary signals and none of the 8 novel loci had minor allele frequencies (MAF) < 5%. Of 802 known European height signals, 643 displayed directionally consistent associations with height, of which 205 were nominally significant (p < 0.05) in the African ancestry sex-combined sample. Furthermore, 148 of 241 loci contained ≤20 variants in the credible sets that jointly account for 99% of the posterior probability of driving the associations. In summary, trans-ethnic meta-analyses revealed novel signals and further improved fine-mapping of putative causal variants in loci shared between African and European ancestry populations.
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http://dx.doi.org/10.1016/j.ajhg.2021.02.011DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8059339PMC
April 2021

Gossypiboma with perforation of the umbilicus mimicking a complicated urachal cyst: a case report.

BMC Surg 2020 Oct 17;20(1):242. Epub 2020 Oct 17.

Department of Surgery, College of Medicine and Allied Health Sciences, University of Sierra Leone and Connaught Hospital, University of Sierra Leone Teaching Hospitals Complex, Freetown, Sierra Leone.

Background: A retained surgical sponge, also known as a gossypiboma, is a rare cause of serious postoperative complications. Diverse retained surgical materials including instruments such as clamps and sutures have been reported, but surgical sponges are the most common material. We report an unusual case of a gossypiboma mimicking a complicated urachal cyst that led to perforation of the umbilicus.

Case Presentation: A 38-year-old female patient presented in our facility with a palpable periumbilical mass and discharge of pus from the umbilicus for 7 months after an open appendectomy. Since the onset of symptoms, the patient had been treated conservatively in a peripheral hospital where she had been operated on. As no improvement was seen, an ultrasound scan was performed that suggested an intraperitoneal abscess adjacent to the umbilicus. Consequently, the patient was referred to our specialist outpatient department for surgical intervention. Suspecting a complicated urachal cyst, an exploratory laparotomy was performed but revealed a retained surgical sponge as the underlying cause. The gossypiboma was resected, and the postoperative period was unremarkable.

Conclusion: This case demonstrates that gossypibomas, even though rare, continue to occur. They may clinically and radiologically mimic other pathologies, especially abscesses and tumors. Preventive measures as well as the inclusion of gossypibomas in the differential diagnosis of intraabdominal masses or fistulation detected in patients with a history of surgery are of utmost importance to minimize morbidity, mortality, and potential medicolegal implications.
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http://dx.doi.org/10.1186/s12893-020-00904-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7568021PMC
October 2020

Impact of axillary node-positivity and surgical resection margins on survival of women treated for breast cancer in Ibadan, Nigeria.

Ecancermedicalscience 2020 5;14:1084. Epub 2020 Aug 5.

Department of Surgery, College of Medicine, University of Ibadan and University College Hospital, Ibadan, Nigeria.

Introduction: Oncologic surgical extirpation, the mainstay of loco-regional disease control in breast cancer, is aimed at achieving negative margins and lymph node clearance. Even though axillary lymph nodal metastasis is a critical index of prognostication, establishing the impact of lymph node ratio (LNR) and adequate surgical margins on disease-specific survivorship would be key to achieving longer survival. This study examines the prognostic role of pN (lymph nodes positive for malignancy), LNR and resection margin on breast cancer survival in a tertiary hospital in Ibadan, Nigeria.

Methods: We conducted a longitudinal cohort study of 225 patients with breast carcinoma, documented clinico-pathologic parameters and 5-year follow up outcomes - distant metastasis and survival. Chi-square test and logistic regression analysis were used to evaluate the interaction of resection margin and proportion of metastatic lymph nodes with patients' survival. The receiver operating characteristic curve was plotted to determine the proportion of metastatic lymph nodes which predicted survival. The survival analysis was done using Kaplan-Meier method.

Results: Sixty (26.7%) patients of the patients had positive resection margins, with the most common immuno-histochemical type being Lumina A. 110 (49%) patients had more than 10 axillary lymph nodes harvested. The mean age was 48.6 ± 11.8 years. Tumour size (p = 0.018), histological type ( = 0.015), grade ( = 0.006), resection margin ( = 0.023), number of harvested nodes ( < 0.01), number of metastatic nodes ( < 0.001) and loco-regional recurrence ( < 0.01) are associated with survival. The overall 5-year survival was 65.3%.

Conclusion: Unfavourable survival outcomes following breast cancer treatment is multifactorial, including the challenges faced in the multimodal treatment protocol received by our patients.
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http://dx.doi.org/10.3332/ecancer.2020.1084DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7434507PMC
August 2020

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

JCO Glob Oncol 2020 03;6:387-394

Center for Clinical Cancer Genetics and Global Health, Department of Medicine, University of Chicago, Chicago, IL.

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 ( < .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.
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http://dx.doi.org/10.1200/JGO.19.00260DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7126761PMC
March 2020

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

Int J Cancer 2019 12 27;145(12):3321-3333. Epub 2019 Jun 27.

Center for Clinical Cancer Genetics & Global Health, Department of Medicine, University of Chicago, Chicago, IL.

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 (h = 0.575, p = 0.010) and the combined APOBEC signatures (h = 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 ). 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.
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http://dx.doi.org/10.1002/ijc.32498DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6851589PMC
December 2019

Outcome of Cerebral Metastasectomy in Select Cases of Brain Metastases from Breast Cancer in Ibadan, Nigeria.

World Neurosurg 2019 Jul 4;127:186-193. Epub 2019 Apr 4.

Division of Oncological Surgery, Department of Surgery, College of Medicine, University of Ibadan/University College Hospital Ibadan, Ibadan, Nigeria.

Background: Brain metastasis (BM) from breast cancer is increasingly encountered clinically because of the continuing success in the oncological control of the primary disease. Data-driven reports on the surgical treatment of BM from breast cancer are sparse in sub-Saharan Africa.

Methods: This is a prospective cohort study of the outcome of surgical excision of BM from breast cancer in an academic surgical practice in Ibadan, Nigeria.

Results: A total of 12 consecutive cerebral metastasectomies, all in females with primary breast cancer, were recorded over the study period. The median age (range) at breast cancer diagnosis was 41 (27-72) years, and the time interval from primary disease to BM was 19 (12-29) months. The BM was the first site of systemic disease progression in all, and was heralded by headache, seizures, and hemiparesis in more than two-thirds of the patients. The brain lesions were multiple in a quarter: >4 cm large in 42% and were located supratentorial in >80%. They all achieved good recovery and in-hospital outcome after surgical lesionectomy-infra- and supratentorial craniotomies-but only two-thirds could access postsurgical adjuvant whole brain radiation therapy. Median survival after cerebral metastasectomy was 18 (11-55) months, and more than a quarter were alive for ≥3years. These survival statistics were significantly better than those of a contemporary cohort of our patients with breast cancer who also had BMs that were not surgically treated for various clinical and logistic limitations.

Conclusions: Surgical resection is feasible for BM from breast cancer even in low-resource clinical practice. It has a salutary effect on the patients' quality of life.
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http://dx.doi.org/10.1016/j.wneu.2019.03.279DOI Listing
July 2019

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

Nat Commun 2019 01 14;10(1):288. Epub 2019 Jan 14.

Department of Surgery, Lagos State University Teaching Hospital, Ikeja, Lagos, Nigeria.

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.
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http://dx.doi.org/10.1038/s41467-018-07886-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6331546PMC
January 2019

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

Nat Commun 2018 10 16;9(1):4181. Epub 2018 Oct 16.

Department of Surgery, Lagos State University Teaching Hospital, Ikeja, Lagos, Nigeria.

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.
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http://dx.doi.org/10.1038/s41467-018-06616-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6191428PMC
October 2018

Inherited Breast Cancer in Nigerian Women.

J Clin Oncol 2018 10 21;36(28):2820-2825. Epub 2018 Aug 21.

Yonglan Zheng, Shengfeng Wang, Dezheng Huo, Toshio F. Yoshimatsu, Jing Zhang, Gabriela E.S. Felix, and Olufunmilayo I. Olopade, The University of Chicago, Chicago, IL; Tom Walsh, Suleyman Gulsuner, Silvia Casadei, Ming K. Lee, and Mary-Claire King, University of Washington, Seattle, WA; Temidayo O. Ogundiran, Adeyinka Ademola, Adeyinka G. Falusi, Abideen O. Oluwasola, Adewumi Adeoye, Abayomi Odetunde, Chinedum P. Babalola, Oladosu A. Ojengbede, Stella Odedina, Imaria Anetor, University of Ibadan; Clement A. Adebamowo, Centre for Bioethics and Research, Ibadan, Oyo, Nigeria, and University of Maryland School of Medicine, Baltimore, MD; and Gabriela E.S. Felix, Fundação Oswaldo Cruz and Universidade Federal da Bahia, Bahia, Brazil.

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.
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http://dx.doi.org/10.1200/JCO.2018.78.3977DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6161833PMC
October 2018

Knowledge of Genetic Counseling Among Patients With Breast Cancer and Their Relatives at a Nigerian Teaching Hospital.

J Glob Oncol 2018 07;4:1-8

Prisca Adejumo, Abimbola Oluwatosin, Babatunde Adedokun, College of Medicine, University of Ibadan, Ibadan; Toyin Aniagwu, Omolara Fagbenle, Olubunmi Ajayi, Dasola Ogungbade, Adeyoola Oluwamotemi, Funmilola Olatoye-Wahab, Abiodun Oni, Oluyemi Olajide, and Temidayo Ogundiran, University College Hospital, Oyo, Nigeria; and Olufunmilayo Olopade, The University of Chicago, Chicago, IL.

Breast cancer prevalence continues to increase globally, and a significant proportion of the disease has been linked to genetic susceptibility. As we enter the era of precision medicine, genetics knowledge and skills are increasingly essential for achieving optimal cancer prevention and care. However, in Nigeria, patients with breast cancer and their relatives are less knowledgeable about genetic susceptibility to chronic diseases. This pilot study collected qualitative data during in-depth interviews with 21 participants. Of these, 19 participants were patients with breast cancer and two were relatives of patients with breast cancer. Participants were asked questions regarding their knowledge of breast cancer, views on heredity and breast cancer, and views on genetic counseling. Participants' family histories were used as a basis with which to assess their hereditary risk of breast cancer. Participant responses were audio recorded and transcribed manually. The study evaluated patients' and relatives' knowledge of genetic counseling and the use of family history for the assessment of familial risk of breast cancer. This will serve as a guide to the processes of establishing a cancer risk assessment clinic.
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http://dx.doi.org/10.1200/JGO.17.00158DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6223535PMC
July 2018

Genetic variation in the Hippo pathway and breast cancer risk in women of African ancestry.

Mol Carcinog 2018 10 14;57(10):1311-1318. Epub 2018 Jun 14.

Center for Clinical Cancer Genetics and Global Health, Department of Medicine, University of Chicago, Chicago, Illinois.

Gene expression changes within the Hippo pathway were found to be associated with large tumor size and metastasis in breast cancer. The combined effect of genetic variants in genes of this pathway may have a causal role in breast cancer development. We examined 7086 SNPs that were not highly correlated (r  < 0.8) in 35 Hippo pathway genes using data from the genome-wide association study of breast cancer from the Root Consortium, which includes 3686 participants of African ancestry from Nigeria, United States of America, and Barbados: 1657 cases (403 estrogen receptor-positive [ER+], 374 ER-) and 2029 controls. Gene-level analyses were conducted using improved AdaJoint test for large-scale genetic association studies adjusting for age, study site and the first four eigenvectors from the principal component analysis. SNP-level analyses were conducted with logistic regression. The Hippo pathway was significantly associated with risk of ER+ breast cancer (pathway-level P = 0.019), with WWC1 (P = 0.04) being the leading gene. The pathway-level significance was lost without WWC1 (P = 0.12). rs147106204 in the WWC1 gene was the most statistically significant SNP after gene-level adjustment for multiple comparisons (OR = 0.53, 95%CI = 0.41-0.70, P  = 0.025). We found evidence of an association between genetic variations in the Hippo pathway and ER+ breast cancer. Moreover, WWC1 was identified as the most important genetic susceptibility locus highlighting the importance of genetic epidemiology studies of breast cancer in understudied populations.
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http://dx.doi.org/10.1002/mc.22845DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6662580PMC
October 2018

Development of a Breast Cancer Risk Prediction Model for Women in Nigeria.

Cancer Epidemiol Biomarkers Prev 2018 06 20;27(6):636-643. Epub 2018 Apr 20.

Center for Clinical Cancer Genetics and Global Health, Department of Medicine, University of Chicago, Chicago, Illinois.

Risk prediction models have been widely used to identify women at higher risk of breast cancer. We aimed to develop a model for absolute breast cancer risk prediction for Nigerian women. A total of 1,811 breast cancer cases and 2,225 controls from the Nigerian Breast Cancer Study (NBCS, 1998-2015) were included. Subjects were randomly divided into the training and validation sets. Incorporating local incidence rates, multivariable logistic regressions were used to develop the model. The NBCS model included age, age at menarche, parity, duration of breastfeeding, family history of breast cancer, height, body mass index, benign breast diseases, and alcohol consumption. The model developed in the training set performed well in the validation set. The discriminating accuracy of the NBCS model [area under ROC curve (AUC) = 0.703, 95% confidence interval (CI), 0.687-0.719] was better than the Black Women's Health Study (BWHS) model (AUC = 0.605; 95% CI, 0.586-0.624), Gail model for white population (AUC = 0.551; 95% CI, 0.531-0.571), and Gail model for black population (AUC = 0.545; 95% CI, 0.525-0.565). Compared with the BWHS and two Gail models, the net reclassification improvement of the NBCS model were 8.26%, 13.45%, and 14.19%, respectively. We have developed a breast cancer risk prediction model specific to women in Nigeria, which provides a promising and indispensable tool to identify women in need of breast cancer early detection in Sub-Saharan Africa populations. Our model is the first breast cancer risk prediction model in Africa. It can be used to identify women at high risk for breast cancer screening. .
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http://dx.doi.org/10.1158/1055-9965.EPI-17-1128DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6086588PMC
June 2018

Genetic variants demonstrating flip-flop phenomenon and breast cancer risk prediction among women of African ancestry.

Breast Cancer Res Treat 2018 Apr 4;168(3):703-712. Epub 2018 Jan 4.

Department of Public Health Sciences, University of Chicago, 5841 S. Maryland Ave, MC 2007, Chicago, IL, 60637, USA.

Background: Few studies have evaluated the performance of existing breast cancer risk prediction models among women of African ancestry. In replication studies of genetic variants, a change in direction of the risk association is a common phenomenon. Termed flip-flop, it means that a variant is risk factor in one population but protective in another, affecting the performance of risk prediction models.

Methods: We used data from the genome-wide association study (GWAS) of breast cancer in the African diaspora (The Root consortium), which included 3686 participants of African ancestry from Nigeria, USA, and Barbados. Polygenic risk scores (PRSs) were constructed from the published odds ratios (ORs) of four sets of susceptibility loci for breast cancer. Discrimination capacity was measured using the area under the receiver operating characteristic curve (AUC).

Results: Flip-flop phenomenon was observed among 30~40% of variants across studies. Using the 34 variants with consistent directionality among previous studies, we constructed a PRS with AUC of 0.531 (95% confidence interval [CI]: 0.512-0.550), which is similar to the PRS using 93 variants and ORs from European ancestry populations (AUC = 0.525, 95% CI: 0.506-0.544). Additionally, we found the 34-variant PRS has good discriminative accuracy in women with family history of breast cancer (AUC = 0.586, 95% CI: 0.532-0.640).

Conclusions: We found that PRS based on variants identified from prior GWASs conducted in women of European and Asian ancestries did not provide a comparable degree of risk stratification for women of African ancestry. Further large-scale fine-mapping studies in African ancestry populations are desirable to discover population-specific genetic risk variants.
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http://dx.doi.org/10.1007/s10549-017-4638-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5916755PMC
April 2018

Association of Pancreatic Cancer Susceptibility Variants with Risk of Breast Cancer in Women of European and African Ancestry.

Cancer Epidemiol Biomarkers Prev 2018 01 18;27(1):116-118. Epub 2017 Dec 18.

Center for Clinical Cancer Genetics and Global Health, Department of Medicine, University of Chicago, Chicago, Illinois.

Pancreatic cancer mutation signatures closely resemble breast cancer, suggesting that both cancers may have common predisposition mechanisms that may include commonly inherited SNPs. We examined 23 genetic variants known to be associated with pancreatic cancer as breast cancer risk factors in the Root genome-wide association study (GWAS; 1,657 cases and 2,029 controls of African diaspora) and GAME-ON/DRIVE GWAS (16,003 cases and 41,335 controls of European ancestry). None of the pancreatic cancer susceptibility variants were individually associated with breast cancer risk after adjustment for multiple testing (at α = 0.002) in the two populations. In Root GWAS, a change by one SD in the polygenic risk score (PRS) was not significantly associated with breast cancer. In addition, we did not observe a trend in the relationship between PRS percentiles and breast cancer risk. The association between reported pancreatic cancer genetic susceptibility variants and breast cancer development in women of African or European ancestry is likely weak, if it does exist. Known GWAS-derived susceptibility variants of pancreatic cancer do not explain its shared genetic etiology with breast cancer. .
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http://dx.doi.org/10.1158/1055-9965.EPI-17-0755DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6644034PMC
January 2018

Genetic variation in the vitamin D related pathway and breast cancer risk in women of African ancestry in the root consortium.

Int J Cancer 2018 01 23;142(1):36-43. Epub 2017 Sep 23.

Center for Clinical Cancer Genetics & Global Health, Department of Medicine, University of Chicago, Chicago, IL.

The vitamin D related pathway has been evaluated in carcinogenesis but its genetic contribution remains poorly understood. We examined single-nucleotide polymorphisms (SNPs) in the vitamin D related pathway genes using data from a genome-wide association study (GWAS) of breast cancer in the African Diaspora that included 3,686 participants (1,657 cases). Pathway- and gene-level analyses were conducted using the adaptive rank truncated product test. Odds ratios (OR) and 95% confidence intervals (CI) were estimated at SNP-level. After stringent Bonferroni corrections, we observed no significant association between variants in the vitamin D pathway and breast cancer risk at the pathway-, gene-, or SNP-level. In addition, no association was found for either the reported signals from GWASs of vitamin D related traits, or the SNPs within vitamin D receptor (VDR) binding regions. Furthermore, a decrease in genetically predicted 25(OH)D levels by Mendelian randomization was not associated with breast cancer (p = 0.23). However, an association for breast cancer with the pigment synthesis/metabolism pathway almost approached significance (pathway-level p = 0.08), driven primarily by a nonsense SNP rs41302073 in TYRP1, with an OR of 1.54 (95% CI = 1.24-1.91, p  = 0.007). In conclusion, we found no evidence to support an association between vitamin D status and breast cancer risk in women of African ancestry, suggesting that vitamin D is unlikely to have significant effect on breast carcinogenesis. Interestingly, TYRP1 might be related to breast cancer through a non-vitamin D relevant mechanism but further studies are needed.
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http://dx.doi.org/10.1002/ijc.31038DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5755399PMC
January 2018

A functionally significant SNP in TP53 and breast cancer risk in African-American women.

NPJ Breast Cancer 2017 27;3. Epub 2017 Feb 27.

Department of Medicine, University of Chicago, Chicago, , IL 60637 USA.

A coding region polymorphism exists in the gene (Pro47Ser; rs1800371) in individuals of African descent, which reduces p53 tumor suppressor function in a mouse model. It has been unclear whether this functionally significant polymorphism alters cancer risk in humans. This analysis included 6907 women with breast cancer and 7644 controls from the AMBER, ROOT, and AABC consortia. We used multivariable logistic regression to estimate associations between the TP53 Pro47Ser allele and overall breast cancer risk. Because polymorphisms in tend to be associated with cancer risk in pre-menopausal women, we also limited our analyses to this population in the AMBER and ROOT consortia, where menopausal status was known, and conducted a fixed effects meta-analysis. In an analysis of all women in the AMBER, ROOT, and AABC consortia, we found no evidence for association of the Pro47Ser variant with breast cancer risk. However, when we restricted our analysis to only pre-menopausal women from the AMBER and ROOT consortia, there was a per allele odds ratio of 1.72 (95% confidence interval 1.08-2.76; -value = 0.023). Although the Pro47Ser variant was not associated with overall breast cancer risk, it may increase risk among pre-menopausal women of African ancestry. Following up on more studies in human populations may better elucidate the role of this variant in breast cancer etiology. However, because of the low frequency of the polymorphism in women of African ancestry, its impact at a population level may be minimal.
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http://dx.doi.org/10.1038/s41523-017-0007-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5445618PMC
February 2017

Association of breast cancer risk and the mTOR pathway in women of African ancestry in 'The Root' Consortium.

Carcinogenesis 2017 08;38(8):789-796

To whom correspondence should be addressed. Tel: +1 773 702 1632; Fax: +1 773 834 1659; Email:

Functional studies have elucidated the role of the mammalian target of rapamycin (mTOR) pathway in breast carcinogenesis, but to date, there is a paucity of data on its contribution to breast cancer risk in women of African ancestry. We examined 47628 SNPs in 61 mTOR pathway genes in the genome wide association study of breast cancer in the African Diaspora study (The Root consortium), which included 3686 participants (1657 cases). Pathway- and gene-level analyses were conducted using the adaptive rank truncated product (ARTP) test for 10994 SNPs that were not highly correlated (r2 < 0.8). Odds ratio (OR) and 95% confidence interval (CI) were estimated with logistic regression for each single-nucleotide polymorphism. The mTOR pathway was significantly associated with overall and estrogen receptor-negative (ER-) breast cancer risk (P = 0.003 and 0.03, respectively). PRKAG3 (Padj = 0.0018) and RPS6KA3 (Padj = 0.061) were the leading genes for the associations with overall breast cancer risk and ER- breast cancer risk, respectively. rs190843378 in PRKAG3 was statistically significant after gene-level adjustment for multiple comparisons (OR = 0.50 for each T allele, 95% CI = 0.38-0.66, Padj = 3.6E-05), with a statistical power of 0.914. These results provide new insights on the biological relevance of the mTOR pathway in breast cancer progression and underscore the need for more genetic epidemiology studies of breast cancer in the African Diaspora.
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http://dx.doi.org/10.1093/carcin/bgx055DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5862308PMC
August 2017

Characterizing Genetic Susceptibility to Breast Cancer in Women of African Ancestry.

Cancer Epidemiol Biomarkers Prev 2017 07 4;26(7):1016-1026. Epub 2017 Apr 4.

Division of Epidemiology, Department of Medicine, Vanderbilt Epidemiology Center, and Vanderbilt-Ingram Cancer Center, Vanderbilt University School of Medicine, Nashville, Tennessee.

Genome-wide association studies have identified approximately 100 common genetic variants associated with breast cancer risk, the majority of which were discovered in women of European ancestry. Because of different patterns of linkage disequilibrium, many of these genetic markers may not represent signals in populations of African ancestry. We tested 74 breast cancer risk variants and conducted fine-mapping of these susceptibility regions in 6,522 breast cancer cases and 7,643 controls of African ancestry from three genetic consortia (AABC, AMBER, and ROOT). Fifty-four of the 74 variants (73%) were found to have ORs that were directionally consistent with those previously reported, of which 12 were nominally statistically significant ( < 0.05). Through fine-mapping, in six regions (), we observed seven markers that better represent the underlying risk variant for overall breast cancer or breast cancer subtypes, whereas in another two regions (), we identified suggestive evidence of signals that are independent of the reported index variant. Overlapping chromatin features and regulatory elements suggest that many of the risk alleles lie in regions with biological functionality. Through fine-mapping of known susceptibility regions, we have revealed alleles that better characterize breast cancer risk in women of African ancestry. The risk alleles identified represent genetic markers for modeling and stratifying breast cancer risk in women of African ancestry. .
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http://dx.doi.org/10.1158/1055-9965.EPI-16-0567DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5500414PMC
July 2017

Genome-wide association studies in women of African ancestry identified 3q26.21 as a novel susceptibility locus for oestrogen receptor negative breast cancer.

Hum Mol Genet 2016 11;25(21):4835-4846

Department of Epidemiology, Gillings School of Global Public Health, and Lineberger Comprehensive Cancer Center, University of North Carolina, Chapel Hill, NC, USA.

Multiple breast cancer loci have been identified in previous genome-wide association studies, but they were mainly conducted in populations of European ancestry. Women of African ancestry are more likely to have young-onset and oestrogen receptor (ER) negative breast cancer for reasons that are unknown and understudied. To identify genetic risk factors for breast cancer in women of African descent, we conducted a meta-analysis of two genome-wide association studies of breast cancer; one study consists of 1,657 cases and 2,029 controls genotyped with Illumina’s HumanOmni2.5 BeadChip and the other study included 3,016 cases and 2,745 controls genotyped using Illumina Human1M-Duo BeadChip. The top 18,376 single nucleotide polymorphisms (SNP) from the meta-analysis were replicated in the third study that consists of 1,984 African Americans cases and 2,939 controls. We found that SNP rs13074711, 26.5 Kb upstream of TNFSF10 at 3q26.21, was significantly associated with risk of oestrogen receptor (ER)-negative breast cancer (odds ratio [OR]=1.29, 95% CI: 1.18-1.40; P = 1.8 × 10 − 8). Functional annotations suggest that the TNFSF10 gene may be involved in breast cancer aetiology, but further functional experiments are needed. In addition, we confirmed SNP rs10069690 was the best indicator for ER-negative breast cancer at 5p15.33 (OR = 1.30; P = 2.4 × 10 − 10) and identified rs12998806 as the best indicator for ER-positive breast cancer at 2q35 (OR = 1.34; P = 2.2 × 10 − 8) for women of African ancestry. These findings demonstrated additional susceptibility alleles for breast cancer can be revealed in diverse populations and have important public health implications in building race/ethnicity-specific risk prediction model for breast cancer.
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http://dx.doi.org/10.1093/hmg/ddw305DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5975608PMC
November 2016

Genetic variants in microRNA and microRNA biogenesis pathway genes and breast cancer risk among women of African ancestry.

Hum Genet 2016 10 5;135(10):1145-59. Epub 2016 Jul 5.

Department of Public Health Sciences, University of Chicago, 5841 S. Maryland Ave., MC 2007, Chicago, IL, 60637, USA.

MicroRNAs (miRNA) regulate breast biology by binding to specific RNA sequences, leading to RNA degradation and inhibition of translation of their target genes. While germline genetic variations may disrupt some of these interactions between miRNAs and their targets, studies assessing the relationship between genetic variations in the miRNA network and breast cancer risk are still limited, particularly among women of African ancestry. We systematically put together a list of 822 and 10,468 genetic variants among primary miRNA sequences and 38 genes in the miRNA biogenesis pathway, respectively; and examined their association with breast cancer risk in the ROOT consortium which includes women of African ancestry. Findings were replicated in an independent consortium. Logistic regression was used to estimate the odds ratio (OR) and 95 % confidence intervals (CI). For overall breast cancer risk, three single-nucleotide polymorphisms (SNPs) in miRNA biogenesis genes DROSHA rs78393591 (OR = 0.69, 95 % CI: 0.55-0.88, P = 0.003), ESR1 rs523736 (OR = 0.88, 95 % CI: 0.82-0.95, P = 3.99 × 10(-4)), and ZCCHC11 rs114101502 (OR = 1.33, 95 % CI: 1.11-1.59, P = 0.002), and one SNP in primary miRNA sequence (rs116159732 in miR-6826, OR = 0.74, 95 % CI: 0.63-0.89, P = 0.001) were found to have significant associations in both discovery and validation phases. In a subgroup analysis, two SNPs were associated with risk of estrogen receptor (ER)-negative breast cancer, and three SNPs were associated with risk of ER-positive breast cancer. Several variants in miRNA and miRNA biogenesis pathway genes were associated with breast cancer risk. Risk associations varied by ER status, suggesting potential new mechanisms in etiology.
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http://dx.doi.org/10.1007/s00439-016-1707-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5021583PMC
October 2016

Breast cancer risk after full-term pregnancies among African women from Nigeria, Cameroon, and Uganda.

Cancer 2015 Jul 17;121(13):2237-43. Epub 2015 Mar 17.

Center for Clinical Cancer Genetics and Global Health, Department of Medicine, University of Chicago, Chicago, Illinois.

Background: The breast cancer (BC) risk profiles of African women differ significantly from those of women of European ancestry. African women are younger at the age of onset and tend to have high parity. The purpose of this study was to examine the relationship between full-term pregnancy (FTP) and the risk of BC.

Methods: A case-control study was conducted among 1995 women with invasive BC and 2631 controls in Nigeria, Cameroon, and Uganda. Odds ratios (ORs) for individual ages at FTP according to the time since delivery were calculated and adjusted for confounders. A fitted spline model was used to assess the impact of the number of pregnancies on BC risk.

Results: In comparison with a nulliparous woman, a parous woman with her first FTP at 20 years showed an OR of 0.76 (95% confidence interval [CI], 0.57-0.99) for developing BC in the following 5 years. Ten years later, this risk was 0.76 (95% CI, 0.58-0.99) and 0.76 (95% CI, 0.58-0.98) for women aged 25 and 30 years, respectively. Similarly, a parous woman with 1 pregnancy had an OR of 0.69 (95% CI, 0.49-0.96), whereas the OR was 0.66 (95% CI, 0.48-0.91) with 2 or 5 pregnancies and 0.67 (95% CI, 0.47-0.94) with 6 pregnancies in comparison with nulliparous women.

Conclusions: In contrast to studies in women of European ancestry, this study showed no transient increase in the risk of developing BC after FTP among African women. Further studies are needed to examine the impact of reproductive factors on early-onset BC in African women.
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http://dx.doi.org/10.1002/cncr.29305DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4573769PMC
July 2015

Social barriers to diagnosis and treatment of breast cancer in patients presenting at a teaching hospital in Ibadan, Nigeria.

Glob Public Health 2015 2;10(3):331-44. Epub 2014 Dec 2.

a Pritzker School of Medicine , University of Chicago , Chicago , IL , USA.

Globally, breast cancer is the most frequent malignancy in women, and stage at diagnosis is a key determinant of outcome. In low- to middle-income countries, including Nigeria, advanced stage diagnosis and delayed treatment represent a significant problem. That social barriers contribute to delay has been noted in previous research; however, few specific factors have been studied. Using semi-structured interviews, this study identifies social barriers to diagnosis and treatment for patients who presented at University College Hospital Ibadan, Nigeria. Transcripts from the interviews were coded and analysed thematically. Thirty-one patients and five physicians were interviewed. The median age of patients was 51 (range: 28 to above 80), 83% were Christian and 17% were Muslim. Preliminary analysis showed that delays in diagnosis reflected a lack of education as well as the utilisation of non-physician medical services such as pharmacists. Delays in treatment were often due to fear of unanticipated surgery and cost. The majority of women did not know the cause of their breast cancer, but some believed it was caused by a spiritual affliction. This study suggests that further education and awareness of breast cancer for both patients and providers is needed in order to increase early stage diagnosis.
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http://dx.doi.org/10.1080/17441692.2014.974649DOI Listing
November 2015

An epidemiologic investigation of physical activity and breast cancer risk in Africa.

Cancer Epidemiol Biomarkers Prev 2014 Dec 21;23(12):2748-56. Epub 2014 Sep 21.

Department of Public Health Sciences, University of Chicago, Chicago, Illinois.

Background: Physical activity (PA) is modifiable and linked to decreased breast cancer risk but its impact has not been investigated among indigenous African populations.

Methods: From 2011 to 2013, 558 cases and 1,014 controls were recruited into the African Breast Cancer Study in Nigeria, Cameroon, and Uganda, and completed a culturally tailored PA questionnaire that assesses habitual PA the year before diagnosis/interview. PA sub-scores (housework, occupational, and leisure PA) and a total PA score were calculated (metabolic equivalent of task, MET-hours/day). Multiple logistic regressions were performed, adjusting for age, body mass index (BMI), study sites, and menopausal status. The models were then stratified by BMI and study site, respectively.

Results: The overall PA score among controls (17.8 MET-hours/day on average) was mainly composed by housework PA and occupational PA with little leisure PA (7.0, 10.3, and 0.5 MET-hours/day, respectively). Multivariable analyses showed that PA was significantly associated with reduced breast cancer risk in both pre- and postmenopausal women (up to 60% risk reduction), with a dose-responsive relationship (Ptrend < 0.001). The inverse association was strong among lean women, less strong but still significant among overweight women, but not existing among obese women. The inverse association held for all intensity-level and domains of PA.

Conclusions: PA of African women mainly consists of housework and work-related activities. The preliminary data show that PA may be significantly associated with reduced breast cancer risk.

Impact: An inverse association between PA and breast cancer risk was observed among indigenous African women, a unique and understudied population.
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http://dx.doi.org/10.1158/1055-9965.EPI-14-0675DOI Listing
December 2014

Alcohol consumption and breast cancer risk among women in three sub-Saharan African countries.

PLoS One 2014 8;9(9):e106908. Epub 2014 Sep 8.

Department of Health Studies, University of Chicago, Chicago, Illinois, United States of America.

Background: Alcohol drinking is linked to the development of breast cancer. However, there is little knowledge about the impact of alcohol consumption on breast cancer risk among African women.

Methods: We conducted a case-control study among 2,138 women with invasive breast cancer and 2,589 controls in Nigeria, Cameroon, and Uganda from 1998 to 2013. A structured questionnaire was used to collect information on alcohol consumption, defined as consuming alcoholic beverages at least once a week for six months or more. Logistic regression was used to estimate adjusted odds ratio (aOR) and 95% confidence interval (CI).

Results: Among healthy controls, the overall alcohol consumption prevalence was 10.4%, and the prevalence in Nigeria, Cameroon, and Uganda were 5.0%, 34.6%, and 50.0%, respectively. Cases were more likely to have consumed alcohol (aOR = 1.62, 95% CI: 1.33-1.97). Both past (aOR = 1.54; 95% CI: 1.19-2.00) and current drinking (aOR = 1.71; 95% CI: 1.30-2.23) were associated with breast cancer risk. A dose-response relationship was observed for duration of alcohol drinking (P-trend <0.001), with 10-year increase of drinking associated with a 54% increased risk (95% CI: 1.29-1.84).

Conclusion: We found a positive relationship between alcohol consumption and breast cancer risk, suggesting that this modifiable risk factor should be addressed in breast cancer prevention programs in Africa.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0106908PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4157846PMC
May 2015
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