MD: Hacettepe University Medical School, Ankara, Turkey
BA: Open University, United Kingdom
PhD: University of Wales College of Medicine, Cardiff, United Kingdom
-American College of Epidemiology (fellow, ACE)
- Society for Epidemiologic Research (SER)
- International Genetic Epidemiology Society (IGES)
- American Society for Histocompatibility and Immunogenetics (ASHI)
- European Federation of Immunogenetics (EFI)
- Genetical Society (UK)
- Human Genome Variation Society
Dr Dorak’s main research involves genetic susceptibility to childhood leukemia. Recent projects examined the genetic polymorphisms in immunogenetics and iron homeostasis related pathways. The genetic basis of previously observed epidemiologic associations (sex effect, birth weight, multiple sclerosis) is also being investigated. Planned research activities include mechanism of the birth weight association, epigenetic markers of susceptibility and regulation of immune response by sex hormones. These studies will be expanded to breast cancer research. New studies in childhood leukemia will also explore the role of genetic factors in higher incidence rates in Hispanic populations. Besides genetic epidemiology, Dr Dorak’s laboratory continues to characterize HLA complex polymorphisms in relation to HLA haplotypes to better understand HLA and disease associations.
Research Interest Description
- The sex effect in susceptibility to cancer, especially childhood cancer, is an overlooked aspect of cancer research. The sex differential in susceptibility (i.e., greater susceptibility of males to cancer) can help to identify risk markers even in case-only studies. To date, Dr Dorak has reported sex-specific associations with HLA genes, immune system genes and iron-related genes in childhood leukemia.
- Genetic and epigenetic variation in immune system is very likely to play a role in greater susceptibility of males to childhood leukemia. Extensive analyses of HLA complex polymorphisms (including those of non-HLA genes) have identified candidate genes for further examination and for their functional assessment. Some of these studies have been carried out in collaboration with Dr Clara Gorodezky in Mexico City. Epigenetic analyses of immune system genes have been planned given the contribution of epigenetics to sex differential in susceptibility to common diseases.
- Sex-specificity of birth weight association in childhood leukemia has been observed in some studies. Dorak Laboratory has been active in examination of the hypothesis that iron-related gene polymorphisms may modulate the sex-specificity of birth weight association. These studies continue in collaboration with Dr M Fatih Okcu at Baylor College of Medicine.
- Iron regulatory gene polymorphisms that increase body iron stores are identified as cancer susceptibility markers after the first report of an association between HFE C282Y and childhood leukemia (Dorak et al, 1999). An extensive analysis of the HFE gene region has provided new insight to the association in childhood leukemia (Davis & Dorak, 2010) and implicated the histone gene variants. This area and additional iron regulatory gene polymorphisms will be further examined in more detailed studies.
- A rare intronic variant within the IRF4 gene has shown a male-specific risk association with childhood leukemia and its functional assessment suggested the involvement of the NF-kB pathway in its sex specificity. This pathway is involved in general cancer susceptibility, and a detailed analysis of genetic variants in this pathway is planned.
Dorak MT & Karpuzoglu E. Gender differences in cancer susceptibility: an inadequately addressed issue. Frontiers in Applied Genetic Epidemiology 2012:3:268
Dorak MT & Amadio WJ. A cautionary note on the reporting of genetic association study results. Journal of Human Genetics 2012;57(7):465-6
Kennedy AE, Singh SK, Dorak MT. Correspondence RE: Genome-wide association study of classical Hodgkin lymphoma and Epstein - Barr virus status-defined subgroups. Journal of the National Cancer Institute 2012;104(11):884-5
Morrison BA, Ucisik-Akkaya E, Flores H, Gorodezky C, Dorak MT (2010) The HLA-DRA and HLA-C-linked multiple sclerosis risk markers are shared by childhood ALL with sex effect, Autoimunity, 43(8), 690-7
Ucisik-Akkaya E, Davis CF, Gorodezky C, Alaez C, Dorak MT (2010) HLA complex-linked heat shock protein genes and childhood acute lymphoblastic leukemia, Cell Stress Chaperones, 15(5), 475-85
Ucisik-Akkaya E, Davis C, Do T, Morrison BA, Stemmer SM, Amadio WJ, Dorak MT (2010) Examination of genetic polymorphisms in newborns for signatures of sex-specific prenatal selection, Molecular Human Reproduction, 16 (10), 770-7
Do TN, Ucisik-Akkaya E, Davis CF, Morrison BA, Dorak MT (2010) An intronic polymorphism of IRF4 gene influences gene transcription in vitro and shows a risk association with childhood acute lymphoblastic leukemia in males, Biochim Biophys Acta Molecular Basis Disease, 1802 (2), 292-300
Davis CF, Dorak MT (2010) An extensive analysis of the hereditary hemochromatosis gene HFE and neighboring histone genes: associations with childhood leukemia, Annals of Hematology, 89 (4), 375-84
Dorak MT, Mackay RK, Relton CL, Worwood M, Parker L, Hall AG (2009) Hereditary hemochromatosis gene (HFE) variants are associated with birth weight and childhood leukemia risk, Pediatric Blood & Cancer, 53 (7), 1242-8
Do TN, Ucisik-Akkaya E, Davis CF, Morrison BA, Dorak MT (2009) TP53 R72P and MDM2 SNP309 polymorphisms in modification of childhood acute lymphoblastic leukemia susceptibility, Cancer Genetics and Cytogenetics, 195 (1), 31-6
Dorak MT, McNally RJQ, Parker L (2007) Childhood Acute Lymphoblastic leukemia and infections, American Journal of Epidemiology, 166 (3), 364-5
Dorak MT, Pearce MS, Hammal DM, McNally RJQ, Parker L (2007) Examination of Gender Effect in Birth Weight and Miscarriage Associations with Childhood Cancer, Cancer Causes & Control, 18 (3), 219-28
Dorak MT, Shao W, Machulla HKG, Lobashevsky ES, Tang J, Park MH, Kaslow RA (2006) Conserved extended haplotypes of the major histocompatibility complex: further characterization, Genes & Immunity, 7 (6), 450-67
Dorak MT (Ed.) (2006) Real-Time PCR, Advanced Methods Series, Oxford (UK), Taylor & Francis, ISBN=041537734X
Dorak MT, Burnett AK, Worwood M, HFE Gene Mutations in Susceptibility to Childhood Leukemia: HuGE Review, Genetics in Medicine, 7(3), 159-168
Kotb M, Norrby-Teglund A, McGeer A, El-Sherbini H, Dorak MT, Khurshid A, Green K, Peeples J, Wade J, Thomson G, Schwartz B, Low DE, An immunogenetic and molecular basis for differences in outcomes of invasive group A streptococcal infections, Nature Medicine, 8(12), 1398-404
Dorak MT, Sproul AM, Gibson BES, Burnett AK, Worwood M, The C282Y mutation of HFE is another male-specific risk factor for childhood ALL, Blood, 94(11), 3957-8
Dorak MT, Lawson T, Machulla HKG, Darke C, Mills KI, Burnett AK, Unravelling an HLA-DR association in childhood acute lymphoblastic leukemia, Blood, 94(2), 694-700