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Breast Cancer Risk Polymorphisms and Interaction with Ionizing Radiation among U.S. Radiologic Technologists

¹ Radiation Epidemiology Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, NIH, Department of Health and Human Services; ² Division of Environmental Health Sciences, School of Public Health, University of Minnesota, Minneapolis, Minnesota; ³ Core Genotyping Facility, Laboratory of Translational Genomics, Gaithersburg, Maryland; ⁴ Research Triangle Institute; ⁵ Department of Radiation Physics, The University of Texas M. D. Anderson Cancer Center, Houston, Texas; ⁶ Bundeswehr Institute of Radiobiology, Munich, Germany; ⁷ HiroSoft International Corporation, Seattle, Washington; ⁸ Cancer Research UK, Strangeways Research Laboratory, Cambridge, UK; and ⁹ Laboratory of Population Genetics, Center for Cancer Research, National Cancer Institute, NIH, Department of Health and Human Services, Bethesda, Maryland

Requests for reprints: Parveen Bhatti, Radiation Epidemiology Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, NIH, Department of Health and Human Services, 6120 Executive Boulevard, Executive Plaza South 7049, Mail Stop Code 7238, Bethesda, MD 20892-7238. Phone: 301-594-7653; Fax: 301-402-0207. E-mail: bhattip{at}mail.NIH.gov

Genome-wide association studies are discovering relationships between single-nucleotide polymorphisms and breast cancer, but the functions of these single-nucleotide polymorphisms are unknown and environmental exposures are likely to be important. We assessed whether breast cancer risk single-nucleotide polymorphisms interacted with ionizing radiation, a known breast carcinogen, among 859 cases and 1,083 controls nested in the U.S. Radiologic Technologists cohort. Among 11 Breast Cancer Association Consortium risk single-nucleotide polymorphisms, we found that the genotype-associated breast cancer risk varied significantly by radiation dose for rs2107425 in the H19 gene (P_interaction = 0.001). H19 is a maternally expressed imprinted mRNA that is closely involved in regulating the IGF2 gene and could exert its influence by this or by some other radiation-related pathway. (Cancer Epidemiol Biomarkers Prev 2008;17(8):2007–11)