Most Genetic Epidemiology Branch investigations evaluate the contributions of host susceptibility and environmental exposure in the development of cancer. In family studies, the host susceptibility measure is frequently an alteration in specific gene(s). These studies tend to be very long term with varying activity. Although two genes associated with melanoma susceptibility have been identified (CDKN2A and CDK4), alterations in these genes are found in only a small percentage of melanoma-prone families. The search for other genes continues;in collaboration with an international consortium (GenoMEL), a search for new melanoma susceptibility genes continues both within families and genome-wide association studies. In the American and Italian melanoma-prone families, we are using novel technologies including array comparative genomic hybridization (aCGH) and next generation sequencing (exomic and whole genome) to search for new high-risk melanoma susceptibility genes. We continue to accrue and evaluate new families in both the U.S., Italy, and Spain. We have continued to evaluate families of individuals with heritable retinoblastoma and melanoma. The study of familial chordoma, a rare, low-grade, malignant bone tumor derived from remnants of the notochord, was expanded to include additional families. Although we have reported duplications of the T gene (brachyury) as a major genetic risk factor for familial chordoma, several families do not have abnormalities in the T gene. We are conducting next generation exomic sequencing in the families without identified high risk susceptibility genes. Studying families with lymphoproliferative cancers has been a long-standing interest. We have collaborated with the Genetic Epidemiology of CLL Consortium to conduct larger studies of familial CLL. We are using exomic and whole genome sequencing to search for high risk susceptibility genes in CLL , HD, WM, and NHL families. We also continued a family study of Xeroderma pigmentosum in collaboration with CCR investigators to assess risk of cancer in XP heterozygotes. Data collection continues.

National Institute of Health (NIH)
National Cancer Institute (NCI)
Investigator-Initiated Intramural Research Projects (ZIA)
Project #
Application #
Study Section
Project Start
Project End
Budget Start
Budget End
Support Year
Fiscal Year
Total Cost
Indirect Cost
Division of Cancer Epidemiology and Genetics
Zip Code
Rotunno, Melissa; Sun, Xuezheng; Figueroa, Jonine et al. (2014) Parity-related molecular signatures and breast cancer subtypes by estrogen receptor status. Breast Cancer Res 16:R74
Shi, Jianxin; Yang, Xiaohong R; Ballew, Bari et al. (2014) Rare missense variants in POT1 predispose to familial cutaneous malignant melanoma. Nat Genet 46:482-6
Liang, Xueying; Pfeiffer, Ruth M; Li, Wen-Qing et al. (2014) Association of genetic variants in CDK6 and XRCC1 with the risk of dysplastic nevi in melanoma-prone families. J Invest Dermatol 134:481-7
Goldstein, Alisa M; Tucker, Margaret A (2013) Dysplastic nevi and melanoma. Cancer Epidemiol Biomarkers Prev 22:528-32
Goldin, Lynn R; McMaster, Mary L; Caporaso, Neil E (2013) Precursors to lymphoproliferative malignancies. Cancer Epidemiol Biomarkers Prev 22:533-9
Iles, Mark M; Law, Matthew H; Stacey, Simon N et al. (2013) A variant in FTO shows association with melanoma risk not due to BMI. Nat Genet 45:428-32, 432e1
Hill, Victoria K; Gartner, Jared J; Samuels, Yardena et al. (2013) The genetics of melanoma: recent advances. Annu Rev Genomics Hum Genet 14:257-79
Puntervoll, Hanne Eknes; Yang, Xiaohong R; Vetti, Hildegunn Høberg et al. (2013) Melanoma prone families with CDK4 germline mutation: phenotypic profile and associations with MC1R variants. J Med Genet 50:264-70
Slager, Susan L; Caporaso, Neil E; de Sanjose, Silvia et al. (2013) Genetic susceptibility to chronic lymphocytic leukemia. Semin Hematol 50:296-302
Kristinsson, Sigurdur Y; Tang, Min; Pfeiffer, Ruth M et al. (2012) Monoclonal gammopathy of undetermined significance and risk of infections: a population-based study. Haematologica 97:854-8

Showing the most recent 10 out of 28 publications