Recruiting population controls for case-control studies in sub-Saharan Africa:The Ghana Breast Health Study

BackgroundIn case-control studies, population controls can help ensure generalizability; however, the selection of population controls can be challenging in environments that lack population registries. We developed a population enumeration and sampling strategy to facilitate use of population controls in a breast cancer case-control study conducted in Ghana.MethodsHousehold enumeration was conducted in 110 census-defined geographic areas within Ghana’s Ashanti, Central, Eastern, and Greater Accra Regions. A pool of potential controls (women aged 18 to 74 years, never diagnosed with breast cancer) was selected from the enumeration using systematic random sampling and frequency-matched to the anticipated distributions of age and residence among cases. Multiple attempts were made to contact potential controls to assess eligibility and arrange for study participation. To increase participation, we implemented a refusal conversion protocol in which initial non-participants were re-approached after several months.Results2,528 women were sampled from the enumeration listing, 2,261 (89%) were successfully contacted, and 2,106 were enrolled (overall recruitment of 83%). 170 women were enrolled through refusal conversion. Compared with women enrolled after being first approached, refusal conversion enrollees were younger and less likely to complete the study interview in the study hospital (13% vs. 23%). The most common reasons for non-participation were lack of interest and lack of time.ConclusionsUsing household enumeration and repeated contacts, we were able to recruit population controls with a high participation rate. Our approach may provide a blue-print for others undertaking epidemiologic studies in populations that lack accessible population registries.</div

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

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

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

Human papillomavirus genotype distribution among women with and without cervical cancer: Implication for vaccination and screening in Ghana

Introduction Determining the high-risk human papillomavirus (HR-HPV) genotypes burden in women with and without cervical cancer afford a direct comparison of their relative distributions. This quest is fundamental to implementing a future population-based cervical cancer prevention strategy in Ghana. We estimated the cervical cancer risk by HPV genotypes, and the HPV vaccine-preventable proportion of cervical cancer diagnosed in Ghana. Materials and methods An unmatched case-control study was conducted at the two largest cervical cancer treatment centres in Ghana from 1st October 2014 to 31st May 2015. Cases were women diagnosed with cervical cancer and controls were women without cervical cancer who were seeking care at the two hospitals. Nested multiplex polymerase chain reaction (NM-PCR) was used to detect HPV infection in cervical samples. Logistic regression was used to determine the association between the risk of cervical cancer and identified HPV infection. P ≤0.05 was considered statistically significant. Results HPV deoxyribonucleic acid (DNA) data were analysed for 177 women with cervical cancer (cases) and 201 without cancer (controls). Cervical cancer was diagnosed at older ages compared to the age at which controls were recruited (median ages, 57 years vs 34 years; p Conclusion Women with cervical cancer in Ghana have HPV infection with multiple genotypes, including some non-vaccine genotypes, with an estimated cervical cancer risk of about six- to ten-fold in the presence of a positive HPV test. HPV DNA tests and multivalent vaccine targeted at HPV 16, 18, 45 and 35 genotypes will be essential in Ghana’s cervical cancer control programme. Large population-based studies are required in countries where cervical cancer is most prevalent to determine non-vaccine HPV genotypes which should be considered for the next-generation HPV vaccines

Receptor-defined subtypes of breast cancer in indigenous populations in Africa: a systematic review and meta-analysis.

BACKGROUND: Breast cancer is the most common female cancer in Africa. Receptor-defined subtypes are a major determinant of treatment options and disease outcomes but there is considerable uncertainty regarding the frequency of poor prognosis estrogen receptor (ER) negative subtypes in Africa. We systematically reviewed publications reporting on the frequency of breast cancer receptor-defined subtypes in indigenous populations in Africa. METHODS AND FINDINGS: Medline, Embase, and Global Health were searched for studies published between 1st January 1980 and 15th April 2014. Reported proportions of ER positive (ER+), progesterone receptor positive (PR+), and human epidermal growth factor receptor-2 positive (HER2+) disease were extracted and 95% CI calculated. Random effects meta-analyses were used to pool estimates. Fifty-four studies from North Africa (n=12,284 women with breast cancer) and 26 from sub-Saharan Africa (n=4,737) were eligible. There was marked between-study heterogeneity in the ER+ estimates in both regions (I2>90%), with the majority reporting proportions between 0.40 and 0.80 in North Africa and between 0.20 and 0.70 in sub-Saharan Africa. Similarly, large between-study heterogeneity was observed for PR+ and HER2+ estimates (I2>80%, in all instances). Meta-regression analyses showed that the proportion of ER+ disease was 10% (4%-17%) lower for studies based on archived tumor blocks rather than prospectively collected specimens, and 9% (2%-17%) lower for those with ≥ 40% versus those with <40% grade 3 tumors. For prospectively collected samples, the pooled proportions for ER+ and triple negative tumors were 0.59 (0.56-0.62) and 0.21 (0.17-0.25), respectively, regardless of region. Limitations of the study include the lack of standardized procedures across the various studies; the low methodological quality of many studies in terms of the representativeness of their case series and the quality of the procedures for collection, fixation, and receptor testing; and the possibility that women with breast cancer may have contributed to more than one study. CONCLUSIONS: The published data from the more appropriate prospectively measured specimens are consistent with the majority of breast cancers in Africa being ER+. As no single subtype dominates in the continent availability of receptor testing should be a priority, especially for young women with early stage disease where appropriate receptor-specific treatment modalities offer the greatest potential for reducing years of life lost. Please see later in the article for the Editors' Summary