Many of the investigations in this genetic epidemiology project arise from observations in families at high risk of cancer or in other etiologic studies. A genomewide scan for linkage was conducted by the Melanoma Genetics Consortium. Examination of linkage in 49 Australian pedigrees containing at least three melanoma patients revealed evidence for linkage to chromosome 1p22. Analysis of 33 additional multiplex families from several continents plus fine mapping provided further evidence for linkage, strongest in families with the earliest mean age at diagnosis. The results provide significant evidence of a novel susceptibility gene for melanoma at 1p22. Examination of case-control study data from 718 non-Hispanic white patients with invasive cutaneous melanoma from melanoma clinics in Philadelphia and San Francisco and 945 matched controls from outpatient clinics with similar catchment areas to the cases revealed that for every 10% increase in average annual UVB flux, there was a 19% increase in risk of melanoma in men and a 16% increase in women. Exposure as an adult was as important as exposure as a child. People who tanned well spent much more time outdoors; among women who tanned well, for every 10% increase in hours outdoors, there was a 5.8% increase in melanoma risk. The findings imply that melanoma prevention efforts must include adult exposure and exposure among those who tan well. Analyses of the data from a population-based case-control study of ovarian cancer in Israel of the Jewish population revealed that both carriers and noncarriers of founder BRCA1/2 mutations had reduced risk of ovarian or peritoneal cancer after gynecologic surgery. The magnitude of the reduction depended upon the type and extent of surgery. As a follow-up to a recently completed DCEG comprehensive case-control study of adults with brain tumors, a family-based study of the parents, siblings and adult children of the 480 eligible glioma cases has been conducted. Relatives were interviewed about personal and family medical history and other risk factors and were asked to provide buccal cells as a source of DNA. The relatives will be used as controls for the glioma cases in association studies and in analyses to evaluate the roles of genetic susceptibility and environmental exposures on the risk of gliomas and etiologically related tumors. A case-control study of 183 incident melanoma cases and 179 controls conducted in northeastern Italy identified dysplastic nevi, low propensity to tan, light eye and light skin color as the strongest risk factors for non-familial melanoma in this Mediterranean population. To investigate the genetic basis for these findings, the Asp312Asn and Lys751Gln polymorphisms of the XPD (ERCC2) DNA repair gene were analyzed. XPD variants were associated with increased risk of melanoma in older (>50 years) subjects or subjects with low-tanning ability. The 751Gln allele was associated with elevated melanoma risk among subjects without dysplastic nevi. Linked data from cancer, population, and hospital discharge registries have been obtained from collaborators in Denmark and Sweden which includes cases of lymphoproliferative (LP) cancers including Hodgkin's disease, Non-Hodgkin's Lymphoma, Chronic Lymphocytic Leukemia, and Multiple Myeloma, matched controls, and first degree relatives of cases and controls. Analyses are ongoing to test for increased risks of LP cancers and autoimmune disorders among relatives of cases.

Agency
National Institute of Health (NIH)
Institute
Division of Cancer Epidemiology And Genetics (NCI)
Type
Intramural Research (Z01)
Project #
1Z01CP005803-09
Application #
6952482
Study Section
(GEB)
Project Start
Project End
Budget Start
Budget End
Support Year
9
Fiscal Year
2003
Total Cost
Indirect Cost
Name
Cancer Epidemiology and Genetics
Department
Type
DUNS #
City
State
Country
United States
Zip Code
Goldin, Lynn R; Bjorkholm, Magnus; Kristinsson, Sigurdur Y et al. (2009) Elevated risk of chronic lymphocytic leukemia and other indolent non-Hodgkin's lymphomas among relatives of patients with chronic lymphocytic leukemia. Haematologica 94:647-53
Goldin, Lynn; Bjorkholm, Magnus; Kristinsson, Sigurdur et al. (2009) Germline and somatic JAK2 mutations and susceptibility to chronic myeloproliferative neoplasms. Genome Med 1:55
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Landgren, Ola; Linet, Martha S; McMaster, Mary L et al. (2006) Familial characteristics of autoimmune and hematologic disorders in 8,406 multiple myeloma patients: a population-based case-control study. Int J Cancer 118:3095-8
Landgren, Ola; Engels, Eric A; Caporaso, Neil E et al. (2006) Patterns of autoimmunity and subsequent chronic lymphocytic leukemia in Nordic countries. Blood 108:292-6
Yang, Xiaohong Rose; Charette, Lori A; Garcia-Closas, Montserrat et al. (2006) Construction and validation of tissue microarrays of ductal carcinoma in situ and terminal duct lobular units associated with invasive breast carcinoma. Diagn Mol Pathol 15:157-61
Goldstein, Alisa M; Dondon, Marie-Gabrielle; Andrieu, Nadine (2006) Unconditional analyses can increase efficiency in assessing gene-environment interaction of the case-combined-control design. Int J Epidemiol 35:1067-73
Landi, Maria Teresa; Kanetsky, Peter A; Tsang, Shirley et al. (2005) MC1R, ASIP, and DNA repair in sporadic and familial melanoma in a Mediterranean population. J Natl Cancer Inst 97:998-1007

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