Prostate cancer research – Dr. Pedro Fernandez
Dr. Pedro Fernandez
Confirming and extending Prostate Cancer Genome-Wide Association Studies in South African men
Prostate cancer is a major health problem in the USA, Europe, and numerous parts of the world, including countries in Africa. Globally, the highest frequency of has been shown in African-American men and other populations of African descent in the Caribbean and Brazil. Additionally, it has been demonstrated that prostate cancer is the most common cancer in West African and Southern African men. Studies have identified genetic variants (referred to as single nucleotide polymorphisms or SNPs) and regions on chromosomes that are associated with increased or decreased risk of developing prostate cancer. Most of these findings have been demonstrated in Caucasian populations in North America or Europe, while to a lesser extent these associations have been replicated or novel associations have been reported in African-American men. Few, if any, of these studies have been undertaken in populations residing in Africa.
The aim of the present study is to determine if previously reported prostate cancer genetic association findings can be replicated in South African men. Subsequently, we aim to combine the South African data with data from other populations in Africa in a larger study. The results generated by these investigations might provide valuable insight into the difference in prostate cancer incidence between populations of African versus non-African ancestry. Moreover, the proposed study will foster cooperation and the dissemination of capacity and knowledge between African institutions.
To date we have analyzed 15 genetic variants in the 830 available human deoxyribonucleic acid (DNA) samples. We have performed quality control on the data for the 15 variants screened (12450 genetic analyses). Briefly, on each of the reaction plates we analyze, we include 5% duplicate DNA samples. We then measure how often the identified genetic variant is similar between the original sample and its duplicate sample. If the percentage of genetic variants identified are similar between the originals and the duplicates at less than 90% or there are too many samples between the originals and duplicates that are called “undetermined” by the analysis software (unable to identify the variant due to poor quality DNA), then the data is not used. We will then re-run the analyses of that genetic variant using newly-prepared DNA and then re-assess the data quality. We have identified 4 variants where the quality score fails to meet the acceptable criteria, these need to be re-assessed.
A BScMedSci honours student (Ms. D. du Toit) has recently analyzed two additional genetic variants. Because one of the variants did not show sufficient variation in our screening panel (i.e. showed a preference for one variation when expect to see at least two or three variations of that particular variant in a random sample of unrelated individuals), the student will screen two additional genetic variants (bringing a total of 19 variants investigated in 830 South African samples). Ms. Du Toit has also developed a protocol to sequence (determine individual DNA nucleotides) of the chromosome region flanking the genetic variants she investigated. The sequence analyses should confirm that the analysis software had correctly scored the variations for the samples. These analyses may also determine if there are novel variants in South African samples that are not included in current genetic databases.
- P Fernandez, CF Heyns, M Jalloh, SM Gueye, C Zeigler-Johnson, TR Rebbeck. Forging prostate cancer genetics research capacity in Africa. Joint International Conference of the African and Southern African Societies of Human Genetics, Cape Town, South Africa, 6-9 March 2011 (poster presentation).
- P Fernandez. Confirming and extending Prostate Cancer Genome-Wide Association Studies in South African men. Oral presentation at the 8th African Organization for Research And Training in Cancer (AORTIC) International Conference, Cairo, Egypt, 30 November – 03 December 2011.