Biography

Dr. Sigurdson received her Ph.D. from the University of Texas-Houston School of Public Health in 1997. Her post-doctoral training was in the Department of Epidemiology at The University of Texas M. D. Anderson Cancer Center. Following one year as an Instructor at M. D. Anderson she joined the NCI's Radiation Epidemiology Branch in 1999.

Research Interests

• Molecular epidemiology of breast and thyroid cancer
• Cosmic radiation exposures and cancer risk from medical imaging
• Radiation exposure biomarkers
• Radiosensitivity

One putative cause of human cancer is radiation exposure. Less well understood are inherent susceptibility factors that may disproportionately increase risk among individuals exposed to ionizing radiation. Chief leading candidates for radiation-related study are genes involved in the repair of DNA single and double strand breaks, since this is likely the most important genetic event caused by radiation to result in cell lethality, chromosomal aberrations and mutation. More agnostic approaches including genome-wide association studies (GWAS) will be used increasingly in the future. While few DNA repair genes have been identified by GWAS so far, denser gene coverage and including more rare variants may still yield important discoveries. In addition, I am interested in functional assays that might assess prospectively cancer risk of various sites.

Radiation Exposure and Radiosensitivity

Humans and animals are heterogeneous in their response to ionizing radiation exposure, both in terms of cancer susceptibility and acute tissue damage. For example, genes involved in DNA repair are known to be polymorphic and may confer unknown, but likely modified, function. Persons who carry specific single nucleotide polymorphisms (SNPs) or a collection of them, may be susceptible when exposed to endogenous or exogenous carcinogens, such as radiation. A single SNP can increase cancer risk, but considering the amount of overlap and redundancy in many cellular pathways, single sites of polymorphic variation may not account for many relationships with cancer outcome. But, multiple polymorphic sites in an individual could act in concert to increase or modify the radiation-related risk. In addition, a challenge-type biomarker of susceptibility that integrates multiple pathways may also be informative. We have pursued both these approaches in nested case-control studies of thyroid and breast cancers among our cohort of U.S. Radiologic Technologists.

Cosmic Radiation Exposures

In a collaborative effort with the National Institutes of Occupational Safety and Health, we are investigating breast cancer risk in a cohort of flight attendants who predominantly flew long-haul transcontinental routes. In addition, we will use fluorescence in situ hybridization (FISH) to evaluate stable chromosomal aberrations in senior airline pilots in relation to their radiation dose from flying commercial aircraft.

Radiation exposure biomarkers

Translocations in chromosomes detected by FISH are a measure of radiation exposure and also appear to be an intermediate marker for cancer risk. We have evaluated stable chromosome aberrations, specifically translocations, among a large cohort of radiologic technologists who were the most highly exposed (they worked before 1950 when exposures were the highest) and have affirmed our reconstructed dose estimates. In addition, we have used the translocation levels to detect cytogenetic damage related to radiation exposure from diagnostic x-ray examinations. Medical radiation exposure has collectively increased six-fold since the early 1980s and has now become a significant portion of the total radiation dose to the general public.

Keywords

Breast cancer, thyroid cancer, cosmic radiation, molecular epidemiology, functional assays, radiation biomarkers

Selected Publications

• Sigurdson AJ, Jones IM, Wei Q, Wu X, Spitz MR, Stram DA, Gross MD, Huang W-Y, Gu J, Wang L-E, Thomas CB, Reding DJ, Hayes RB, Caporaso NE. Assays for DNA damage or repair and lung cancer risk: A prospective analysis from the prostate, lung, colorectal, and ovarian cancer screening trial. (Carcinogenesis, 2011, 32(1):69-73
• Sigurdson AJ, Bhatti P, Preston DL, Doody MM, Kampa D, Alexander BH, Petibone D, Yong LC, Edwards AA, Ron E, Tucker JD. Routine diagnostic X-ray examinations and increased frequency of chromosome translocations among U.S. radiologic technologists. Cancer Res 2008 Nov 1;68(21):8825-31.
• Bhatti P, Yong LC, Doody MM, Preston DL, Kampa DM, Ramsey MJ, Ward E, Edwards AA, Ron E, Tucker JD, Sigurdson AJ. Increased chromosome translocations are associated with diagnostic x-ray examinations: a pooled analysis of three studies. Radiat Environ Biophys, 2010 Jul 3 [epub ahead of print].
• Bhatti P, Doody MM, Alexander BH, Yuenger J, Simon SL, Weinstock RM, Rosenstein M, Stovall M, Abend M, Preston DL, Pharoah P, Struewing JP, Sigurdson AJ. Breast cancer risk polymorphisms and interaction with ionizing radiation among U.S. radiologic technologists. Cancer Epidemiol Biomarkers Prev 2008 Aug;17(8):2007-11.
• Yong LC, Sigurdson AJ, Ward EM, Waters MA, Whelan EA, Petersen MR, Bhatti P, Ramsey MJ, Ron E, Tucker JD. Increased frequency of chromosome translocations in airline pilots with long-term flying experience. Occup Environ Med 2009 Jan;66(1):56-62.
• Sigurdson AJ, Land CE, Bhatti P, Pineda M, Brenner A, Carr Z, Gusev BI, Zhumadilov Z, Simon SL, Bouville A, Rutter JL, Ron E, Struewing JP. Thyroid nodules, polymorphic variants in DNA repair and RET-related genes, and interaction with ionizing radiation exposure from nuclear tests in Kazakhstan. Radiat Res 2009 Jan;171(1):77-88.
• Neta G, Brenner AV, Sturgis EM, Pfeiffer R, Hutchinson AA, Kilfoy B, Yeager M, Xu L, Wheeler W, Abend M, Ron E, Tucker MA, Chanock S, Sigurdson AJ. Common genetic variants related to genomic integrity and risk of papillary thyroid cancer. Carcinogenesis June 3 2011, [Epub ahead of print]

Collaborators

DCEG Collaborators

• Mark Little, Ph.D.; Gila Neta, Ph.D.; Ruth Kleinerman, M.P.H.; Michele Doody, M.S.; Martha Linet, M. D.; Peter Inskip, Sc.D.; Kiyohiko Mabuchi, M.D. Dr.P.H.; Michal Freedman, Ph.D.; Neil Caporaso, M.D.; Lene Viega, Ph.D., Preetha Rajaraman, Ph.D.; Steven Simon, Ph.D.; Jay Lubin, Ph.D.

Other NIH Collaborators

• Lynne Pinkerton, M.D., M.P.H.; Lee Yong, Ph.D., National Institute of Occupational Safety and Health, Cincinnati, OH

Other Scientific Collaborators

• Parveen Bhatti, Ph.D. Fred Hutchinson Cancer Research Center, Seattle, WA
• Irene Jones, Ph.D., Lawrence Livermore National Laboratory, Livermore, CA
• James Tucker, Ph.D., Wayne State University, Detroit, MI
• Susan Bailey, Ph.D., Colorado State University, Ft. Collins, CO
• Marilyn Stovall, Ph.D., Margaret Spitz, M.D., M.P.H., University of Texas M. D. Anderson Cancer Center, Houston, TX
• Bruce Alexander, Ph.D., University of Minnesota, Minneapolis, MN
• Leslie Robison, St. Jude Children's Cancer Research Hospital, Memphis, TN
• Yuri Nikiforov, University of Pittsburg Medical Center, Pittsburgh, PA