Heterogeneous genetic architectures and evolutionary genomics of prostate cancer in Sub-Saharan Africa.

Men of African descent have the highest prostate cancer (CaP) incidence and mortality rates, yet the genetic basis of CaP in African men has been understudied. We used genomic data from 3,963 CaP cases and 3,509 controls recruited in Ghana, Nigeria, Senegal, South Africa, and Uganda, to infer ancestry-specific genetic architectures and fine-mapped disease associations. Fifteen independent associations at 8q24.21, 6q22.1, and 11q13.3 reached genome-wide significance, including four novel associations. Intriguingly, multiple lead SNPs are private alleles, a pattern arising from recent mutations and the out-of-Africa bottleneck. These African-specific alleles contribute to haplotypes with odds ratios above 2.4. We found that the genetic architecture of CaP differs across Africa, with effect size differences contributing more to this heterogeneity than allele frequency differences. Population genetic analyses reveal that African CaP associations are largely governed by neutral evolution. Collectively, our findings emphasize the utility of conducting genetic studies that use diverse populations.

Testing the generalizability of ancestry-specific polygenic risk scores to predict prostate cancer in sub-Saharan Africa.

BACKGROUND: Genome-wide association studies do not always replicate well across populations, limiting the generalizability of polygenic risk scores (PRS). Despite higher incidence and mortality rates of prostate cancer in men of African descent, much of what is known about cancer genetics comes from populations of European descent. To understand how well genetic predictions perform in different populations, we evaluated test characteristics of PRS from three previous studies using data from the UK Biobank and a novel dataset of 1298 prostate cancer cases and 1333 controls from Ghana, Nigeria, Senegal, and South Africa. RESULTS: Allele frequency differences cause predicted risks of prostate cancer to vary across populations. However, natural selection is not the primary driver of these differences. Comparing continental datasets, we find that polygenic predictions of case vs. control status are more effective for European individuals (AUC 0.608-0.707, OR 2.37-5.71) than for African individuals (AUC 0.502-0.585, OR 0.95-2.01). Furthermore, PRS that leverage information from African Americans yield modest AUC and odds ratio improvements for sub-Saharan African individuals. These improvements were larger for West Africans than for South Africans. Finally, we find that existing PRS are largely unable to predict whether African individuals develop aggressive forms of prostate cancer, as specified by higher tumor stages or Gleason scores. CONCLUSIONS: Genetic predictions of prostate cancer perform poorly if the study sample does not match the ancestry of the original GWAS. PRS built from European GWAS may be inadequate for application in non-European populations and perpetuate existing health disparities.

Validation of a multi-ancestry polygenic risk score and age-specific risks of prostate cancer: A meta-analysis within diverse populations.

Background: We recently developed a multi-ancestry polygenic risk score (PRS) that effectively stratifies prostate cancer risk across populations. In this study, we validated the performance of the PRS in the multi-ancestry Million Veteran Program and additional independent studies. Methods: Within each ancestry population, the association of PRS with prostate cancer risk was evaluated separately in each case-control study and then combined in a fixed-effects inverse-variance-weighted meta-analysis. We further assessed the effect modification by age and estimated the age-specific absolute risk of prostate cancer for each ancestry population. Results: The PRS was evaluated in 31,925 cases and 490,507 controls, including men from European (22,049 cases, 414,249 controls), African (8794 cases, 55,657 controls), and Hispanic (1082 cases, 20,601 controls) populations. Comparing men in the top decile (90-100% of the PRS) to the average 40-60% PRS category, the prostate cancer odds ratio (OR) was 3.8-fold in European ancestry men (95% CI = 3.62-3.96), 2.8-fold in African ancestry men (95% CI = 2.59-3.03), and 3.2-fold in Hispanic men (95% CI = 2.64-3.92). The PRS did not discriminate risk of aggressive versus nonaggressive prostate cancer. However, the OR diminished with advancing age (European ancestry men in the top decile: ≤55 years, OR = 7.11; 55-60 years, OR = 4.26; >70 years, OR = 2.79). Men in the top PRS decile reached 5% absolute prostate cancer risk ~10 years younger than men in the 40-60% PRS category. Conclusions: Our findings validate the multi-ancestry PRS as an effective prostate cancer risk stratification tool across populations. A clinical study of PRS is warranted to determine whether the PRS could be used for risk-stratified screening and early detection. Funding: This work was supported by the National Cancer Institute at the National Institutes of Health (grant numbers U19 CA214253 to C.A.H., U01 CA257328 to C.A.H., U19 CA148537 to C.A.H., R01 CA165862 to C.A.H., K99 CA246063 to B.F.D, and T32CA229110 to F.C), the Prostate Cancer Foundation (grants 21YOUN11 to B.F.D. and 20CHAS03 to C.A.H.), the Achievement Rewards for College Scientists Foundation Los Angeles Founder Chapter to B.F.D, and the Million Veteran Program-MVP017. This research has been conducted using the UK Biobank Resource under application number 42195. This research is based on data from the Million Veteran Program, Office of Research and Development, and the Veterans Health Administration. This publication does not represent the views of the Department of Veteran Affairs or the United States Government.

Text messaging promoting physician-led brief intervention tobacco cessation: A before-and-after study among physicians in three tertiary hospitals in Nigeria.

Background: Physician-led smoking cessation services are suboptimal in Nigeria. Objectives: This study evaluated a text messaging intervention designed to increase the knowledge and practices of physicians in Nigeria to help smokers quit. Methods: Using a pre-post study design, all physicians (N = 946) in 3 tertiary care hospitals located in 3 geopolitical zones in Nigeria were sent 2-3 text messages weekly over a 13-week period to create awareness and improve cessation practices using the "Ask, Advise and Refer" (AAR) model. The primary outcomes were the awareness of AAR and the proportion of physicians who offered each of the components of the brief intervention (AAR) to at least half of eligible patients. Secondary outcomes included the attitudes and self-reported effects of the messages on motivation to offer AAR to patients who smoke. Results: Of the 946 eligible respondents, only 165 responded to both the before and after intervention surveys (17.4% participation rate). Participants were more likely to indicate awareness of the AAR approach after the intervention (60%) than before (21.2%). Overall, physicians' practice of each component of the AAR changed significantly after the intervention (P < .001; McNemar test). Of the participants, 71.5% reported reading the messages most/all of the time and 84.8% reported that the frequency of the messages was just adequate. Conclusions: A brief and low-cost text messaging intervention to physicians increased the awareness and practice of AAR in those who participated in the study. However, the relatively low participation rate highlights the importance of new research to improve and expand text messaging as an intervention among physicians to help them foster tobacco treatment among their patients.

A Multi-centre Survey of Acceptability of Newborn Screening for Sickle Cell Disease in Nigeria.

Background Sickle cell disease (SCD) is a major genetic disease that manifests early in life and may lead to significant morbidities. One of the health care services that have been effective in reducing the burden of SCD in developed countries is newborn screening (NBS) followed by pneumococcal vaccines, penicillin prophylaxis, and hydroxyurea treatment. Yet, in sub-Saharan African countries, where about 75% of annual affected babies worldwide are born, NBS programmes are largely unavailable. It is not clear whether this is due to technical challenges associated with setting up such programmes, or significant cultural and social barriers to its acceptance in such settings. Objective Our aim was to ascertain the attitudes to and acceptability of NBS in Nigeria among various socio-demographic groups including health professionals, undergraduate students, parents of children with SCD and SCD patients. Methods Data on socio-demographic characteristics, knowledge of SCD and attitude towards NBS were collected using a semi-structured pre-tested questionnaire from April to July 2014 across 15 health institutions and university campuses in Nigeria. Data were collected from 1,301 respondents across Nigeria. Results There was good knowledge of SCD as an inherited blood disorder. Although 86% of respondents (n = 1,119) supported NBS, there was a statistically significant relationship between support for NBS and age (p = 003), educational status (p = 000) and religion (p = 000). Conclusion This study suggests that there is a good acceptability of NBS across Nigeria. The main barriers to its use are likely to be financial and practical, rather than social or cultural.

Tobacco Cessation Interventions in Tertiary Hospitals in Nigeria: An Audit of Patient Records.

BACKGROUND: Patient medical records are an objective tool for the systematic identification and treatment of tobacco users. The aim of this study was to assess brief intervention tobacco cessation activities documented by physicians in some select tertiary hospitals in Nigeria. METHODS: We conducted a cross-sectional descriptive study using information obtained from 1588 randomly selected patient records in six teaching hospitals participating in a study to capacitate physicians to deliver brief advice. Trained data collectors collected data using a uniform checklist prior to the training of the physicians in these hospitals. RESULTS: Of the audited health records, 33.1% of patients had documentation of physicians' inquiry of their tobacco use mostly during out-patient clinics (37%) and by a resident doctor/medical officer (42.9%). Among identified tobacco users, it was documented that 12.9% were offered some form of tobacco cessation advice; readiness to quit was recorded in 2.6%; assistance with quitting was documented for 1.5% of tobacco users, while only 0.8% showed documentation of patient follow-up. Males and patients admitted to the hospital were 1.86 times and 2.14 times respectively more likely to have records of physicians' inquiry of their tobacco use. Patients who had tobacco-related morbidities and the unemployed were also more likely to have records of inquiry of their tobacco use. CONCLUSIONS: There was poor documentation of tobacco use by physicians in these hospitals and many opportunities for brief intervention activities were missed. Efforts to educate the physicians on the importance of documenting tobacco use in clinical notes are recommended. IMPLICATIONS: This study provides empirical evidence showing that there is poor documentation of tobacco use inquiry and brief intervention among physicians in tertiary hospitals in Nigeria. Records showing implementation of the 5A's were abysmally low and opportunities for brief intervention may have been missed. In line with the World Health Organization recommendations of Article 14 of the Framework Convention on Tobacco Control, efforts to promote brief intervention among physicians in tertiary hospitals in Nigeria should include an emphasis on appropriate documentation of tobacco control interventions in patient clinical notes.

Comparison of microalbuminuria among treatment naïve HIV sero-positive and negative adult clients in Faith Alive Foundation Hospital, Jos.

BACKGROUND: This study is to determine microalbuminuria in human immunodeficiency virus (HIV) infected patients before commencement of highly active anti-retroviral treatment (HAART). PATIENTS AND METHODS: Consecutive patients with the HIV infection seen in the HIV counselling and testing (HCT) unit of the Faith Alive Foundation Hospital, Jos, and a similar group of healthy uninfected patients were evaluated for renal disease: Urinary albumin and urinary creatinine were analysed. RESULTS: Of the 200 patients with HIV infection and 100 uninfected controls studied, increased urinary albumin excretion (UAE) was present in 39 (19.5%) of the subjects and 5.0 (5.0%) of controls. The difference between the mean values for the UAE for both subjects and controls [182.3 ± 54.3 and 163.9 ± 39.3 mg/l, respectively (P = 0.006)] was statistically significant. On the other hand the urinary creatinine for both the subjects and controls [11.7 ± 5.2 and 12.0 ± 4.8 mmol/L, respectively (P = 0.6)] was not statistically significant. The difference between the mean urinary albumin/creatinine ratio (UACR) for both subjects and controls [1.8 ± 1.2 mg/mmol and 1.4 ± 0.4 mg/mmol respectively (P = 0.001)] was statistically significant. CONCLUSION/RECOMMENDATION: Increase UAE is a common complication of HIV infection due to a number of factors other than HAART. Early screening for renal disease using microalbuminuria is very useful since the use of medications such as angiotensin converting enzyme inhibitors, which could help reverse progression to end-stage renal disease.

Exposure of Undergraduate Students to Cigarette Adverts: A Case Study of University of Abuja; Nigeria

Context: Cigarette smoking has became prevalent particularly in developing countries where youths get initiated at an earlier age than in the past two decades and there is only rudimentary support for smoking cessation. Although the relationship between cigarette smoking and health hazards is well documented; the incidence of cigarette smoking continues to increase despite global and local tobacco control efforts. Aims: The study objective was to determine the level of exposure of respondents to cigarette smoking and the factors associated with it. Materials and Methods: A pre-tested; self-administered questionnaire was used to collect data on socio-demographic features; knowledge about smoking and exposure to media for health information including exposure to tobacco adverts. Subjects were selected by multistage sampling technique. Results: One-third of the students were current smokers and most of them had poor knowledge of the consequences of smoking. All of the students were exposed to some level smoking adverts through electronic/print media. Over 90 of the students had no exposure to smoking prevention and none of the smokers were exposed to cessation interventions. One-fifth believed they were not at health risk as a result of smoking. The school had no smoking control policy. Conclusions: There was a strong; constant exposure of the youths to cigarette adverts in the media; on the streets; the school and homes. There is need to protect the youths from such excessive exposures to factors that encourage smoking and establish intervention strategies to prevent continued exposure to cigarette adverts

Knowledge and attitudes towards cervical cancer and human papillomavirus: a Nigerian pilot study.

This study aimed to ascertain the knowledge and attitudes of urban and rural dwellers to cervical cancer and HPV in Gwagwalada Area Council of Nigeria. 400 participants aged 15-45 years were selected from Gwagwalada town and the adjourning Giri village to respond to a multi-choice-free response questionnaire designed to obtain information on respondents' biodata, knowledge of STIs, human papilloma virus and cervical cancer, health and communication resources in their communities. This was supplemented by focus group discussions among religious and tribal groups within the urban and rural communities. We found a low level of awareness about HPV and cervical cancer which majority felt could not be prevented. Although awareness of STDs was high in both urban and rural dwellers, condom use was low. The study underscores the need for a well planned and implemented health communication and education program on STIs, HPV and cervical cancer in Nigeria.

Knowledge and attitudes towards cervical cancer and human papillomavirus: a nigerian pilot study

This study aimed to ascertain the knowledge and attitudes of urban and rural dwellers to cervical cancer and HPV in Gwagwalada Area Council of Nigeria. 400 participants aged 15-45 years were selected from Gwagwalada town and the adjourning Giri village to respond to a multi-choice­free response questionnaire designed to obtain information on respondents' biodata, knowledge of STIs, human papilloma virus and cervical cancer, health and communication resources in their communities. This was supplemented by focus group discussions among religious and tribal groups within the urban and rural communities. We found a low level of awareness about HPV and cervical cancer which majority felt could not be prevented. Although awareness of STDs was high in both urban and rural dwellers, condom use was low. The study underscores the need for a well planned and implemented health communication and education program on STIs, HPV and cervical cancer in Nigeria (Afr J Reprod Health 2010; 14[1]:95-108)