Studies of Persons at High Risk of Cancer

Tucker, M A.

Abstract

The purpose of this project is to (a) conduct and coordinate interdisciplinary studies on members of cancer-prone families and other high-risk populations to clarify the role of genetic mechanisms and host-environmental interactions in human carcinogenesis; and (b) assess, quantify, and elucidate the determinants of the cancer risks associated with therapeutic exposure to cytotoxic drugs. Project staff also conduct or collaborate with other EEB investigators in epidemiologic case-control studies of specific cancers or cohort studies of specific exposures that are particularly relevant to this project. A series of project resources has been developed in support of our research, including: (1) a computerized registry of cancer-prone families; (2) a biospecimen repository which processes, stores and distributes biological samples from persons at high risk of cancer; (3) a fibroblast repository/tissue culture facility; and (4) a series of contract-supported laboratories which provide immunologic, cytogenetic, and DNA repair assay capabilities. Persons at high risk of cancer are evaluated clinically and donate biological samples. Clinical, epidemiologic, genetic, and laboratory studies are combined to elucidate mechanisms of cancer susceptibility. The familial melanoma project is a prototype of this approach, in which clinical (dysplastic nevi), genetic (autosomal dominant transmission of a gene possibly linked to the RJ locus) and biologic (enhanced sensitivity to the cytotoxic and mutagenic effects of UV radiation) risk factors have been identified. The therapeutic administration of cytotoxic drugs, many of which are carcinogenic in laboratory animals, provides an opportunity to explore the cancer patients treated with specific cytotoxic drugs are conducted. The leukemogenicity of specific alkylating agents has been documented, differences in leukemogenic potential among various agents identified, and evidence for an increasing risk of leukemia with increasing drug dose obtained.

Funding Agency

• Agency: National Institute of Health (NIH)
• Institute: Division of Cancer Epidemiology And Genetics (NCI)
• Type: Intramural Research (Z01)
• Project #: 1Z01CP004410-10
• Application #: 3963384
• Support Year: 10
• Fiscal Year: 1986

Institution

• Name: Cancer Epidemiology and Genetics
• Country: United States

Publications

Goldin, Lynn R; McMaster, Mary L; Caporaso, Neil E (2013) Precursors to lymphoproliferative malignancies. Cancer Epidemiol Biomarkers Prev 22:533-9

Han, Summer S; Yeager, Meredith; Moore, Lee E et al. (2012) The chromosome 2p21 region harbors a complex genetic architecture for association with risk for renal cell carcinoma. Hum Mol Genet 21:1190-200

Brau-Javier, Cristina N; Gonzales-Chavez, Jose; Toro, Jorge R (2012) Chronic cutaneous pustulosis due to a 175-kb deletion on chromosome 2q13: excellent response to anakinra. Arch Dermatol 148:301-4

Kristinsson, Sigurdur Y; Goldin, Lynn R; Turesson, Ingemar et al. (2012) Familial aggregation of lymphoplasmacytic lymphoma/Waldenström macroglobulinemia with solid tumors and myeloid malignancies. Acta Haematol 127:173-7

Goldin, Lynn R; Kristinsson, Sigurdur Y; Liang, Xueying Sharon et al. (2012) Familial aggregation of acute myeloid leukemia and myelodysplastic syndromes. J Clin Oncol 30:179-83

Lindqvist, Ebba K; Goldin, Lynn R; Landgren, Ola et al. (2011) Personal and family history of immune-related conditions increase the risk of plasma cell disorders: a population-based study. Blood 118:6284-91

Goldin, Lynn R; Lanasa, Mark C; Slager, Susan L et al. (2010) Common occurrence of monoclonal B-cell lymphocytosis among members of high-risk CLL families. Br J Haematol 151:152-8

Kristinsson, Sigurdur Y; Koshiol, Jill; Goldin, Lynn R et al. (2009) Genetics- and immune-related factors in the pathogenesis of lymphoplasmacytic lymphoma/ Waldenström's macroglobulinemia. Clin Lymphoma Myeloma 9:23-6

Kristinsson, Sigurdur Y; Björkholm, Magnus; Goldin, Lynn R et al. (2009) Patterns of hematologic malignancies and solid tumors among 37,838 first-degree relatives of 13,896 patients with multiple myeloma in Sweden. Int J Cancer 125:2147-50

Bradford, Porcia T; Goldstein, Alisa M; McMaster, Mary L et al. (2009) Acral lentiginous melanoma: incidence and survival patterns in the United States, 1986-2005. Arch Dermatol 145:427-34