Office of the Director, HGP
Margaret A. Tucker, Director
Program Staff Directory
Overview and Operating Philosophy
The Human Genetics Program was established in 1996 to provide an expanded focus for interdisciplinary research into the genetic determinants of human cancer. Advances in molecular genetics and related biomedical sciences provide extraordinary opportunities both to explore and identify heritable factors that predispose to cancer as well as to elucidate gene-environment interactions. Program investigators conduct family-based and population-based studies that integrate clinical, epidemiologic, and laboratory approaches to investigate genetic susceptibility to cancer. The Program is organized into the Clinical Genetics Branch, the Genetic Epidemiology Branch, and the Laboratory of Translational Genomics.
The Clinical Genetics Branch became operational in the Fall of 1999 with the recruitment of Dr. Mark H. Greene as Branch Chief, along with scientific and support staff. The Branch focuses on the translation of advances in molecular genetics into evidence-based management strategies, such as screening, prevention, and assessment of behavioral consequences, for persons at increased genetic risk of cancer. In carrying out this research program, molecular and clinical observations in cancer genetics are integrated into interdisciplinary approaches that involve epidemiologic, clinical, genetic, behavioral, statistical, and laboratory methods to define the role of susceptibility genes in cancer etiology. Initial areas of scientific concentration include interdisciplinary studies of cancer-prone families, analyses of genetic polymorphisms as determinants of cancer treatment outcomes, and chemoprevention trials that target genetically at-risk populations.
The Genetic Epidemiology Branch, under the leadership of Dr. Margaret A. Tucker, continued a long record of hereditary cancer research, dating back to the early 1960s, at the NCI. Today, the Branch focuses on families at high risk of cancer, mapping and cloning of predisposing genes, investigating identified genes in the general population, developing new genetic epidemiologic methodologies, conducting pharmacogenetic studies, and identifying late effects of treatment in survivors of cancer. In the area of predisposing genes to environmentally induced cancer, a major effort is under way to understand the role of polymorphic metabolizing genes, such as the cytochrome P450 group, the N-actyl transferases, and the glutathione-S-transferases. Recent accomplishments related to hereditary cancers include defining clinical features and mapping/cloning of genes responsible for retinoblastoma (RB1), Li-Fraumeni syndrome (TP53), neurofibromatosis (NF1 and NF2), melanoma (CDKN2 and CDK4), breast and ovarian cancers (BRCA1 and BRCA2), and Cowden’s disease with breast cancer (PTEN).
The newly formed Laboratory of Translational Genomics (LTG) in the Division of Cancer Epidemiology and Genetics (DCEG) is committed to understanding the contribution of germ-line genetic variation to cancer etiology and outcomes. The mission of the LTG is to investigate the genetic basis of strong association signals identified in candidate gene association studies, loci identified by linkage analyses in high-risk families, or genome-wide association studies (GWAS), particularly the loci identified by the ongoing Cancer Genetic Markers of Susceptibility (CGEMS) program involving GWAS of several major cancers.
