Biography

Dr. Sigurdson Sigurdson received her Ph.D. from the University of Texas 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.

Research Interests

• Molecular epidemiology of breast and thyroid cancer
• High-LET (such as neutron and cosmic radiation) exposures
• Biomarkers of radiation exposure
• Hormonal cancers

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. I am particularly interested in evaluating single nucleotide polymorphisms that might confer subtle deficiencies in base-excision repair, nucleotide excision repair, mismatch repair, homologous recombination and non-homologous end joining as well as genes that regulate cell cycle progression and apoptosis. In addition, I am interested in protein expression and functional assays that might assess prospectively cancer risk of various sites.

Radiation Exposure and DNA Repair Genes

Humans and animals are heterogeneous in their response to ionizing radiation exposure, both in terms of cancer susceptibility and acute tissue damage. Genes involved in DNA repair are known to be polymorphic and some of the allelic variants result in amino acid substitutions that are not evolutionarily conserved 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 the DNA repair 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 risk. In addition, a challenge-type biomarker of susceptibility that integrates multiple pathways may also be informative. We are proposing both these approaches in nested case-control studies of thyroid, breast and non-melanoma skin cancers among our cohort of Radiologic Technologists.

Neutron and Cosmic (High-LET) Radiation Exposures

There is a great deal of speculation about the effects of neutron exposures in human populations. The relative biological effectiveness of neutrons compared to x- or -rays (low-LET radiation) is expected to be large based on animal and cellular studies but there are few instances where it is possible to study neutron exposure in humans. This question becomes important for workers such as astronauts, pilots and flight attendants who are occupationally exposed to neutrons from cosmic radiation.

• 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 compared with university faculty who are infrequent flyers.

Radiation exposure biomarkers

Translocations in chromosomes detected by FISH are also a measure of low-LET radiation exposure and also appear to be an intermediate marker for cancer risk. We are evaluating these stable chromosome aberrations (SCAs) among a large cohort of radiologic technologists who were the most highly exposed (they worked before 1950 when exposures were the highest) and will relate the results to our reconstructed dose estimates. However, SCAs are highly variable despite analytically accounting for age. We plan to determine whether certain SNPs in several pathways related to genomic stability may play a role in the marked variation in SCA levels.

Keywords

Breast cancer, thyroid cancer, cosmic radiation, molecular epidemiology, DNA repair, functional assays

Selected Publications

• Sigurdson AJ, Ron E. "Cosmic radiation exposure and cancer risk among flight crew." In press, Cancer Investigations.
• Sigurdson AJ, Hauptmann M, Chatterjee N, Alexander BH, Doody MM, Rutter JL, Struewing JP. "Kin-cohort estimates for familial breast cancer risk in relation to variants in DNA base excision repair, BRCA1 interacting and growth factor genes." BMC Cancer 2004;4:9 (pp 1-12).
• Sigurdson AJ, Jones IM. "Second cancers after radiotherapy - any evidence for radiation induced genomic instability?" Oncogene 2003;22:7018-7027.
• Sigurdson A, Doody MM, Rao RS, Freedman M, Alexander B, Mohan A, Hauptmann M, Yoshinaga S, Hill D, Tarone R, Mabuchi K, Ron E, Linet MS. "Cancer Incidence in the U. S. Radiologic Technologists Health Study, 1984-1998." Cancer 2003;97:3080-3089.

Collaborators

DCEG Collaborators

• Elaine Ron, 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.; Michael Hauptmann, Ph.D.; Michal Freedman, Ph.D.; Parveen Bhatti; Cecile Ronckers

Other NCI Collaborators

• Jeffery Struewing, M.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

• Irene Jones, Ph.D., Lawrence Livermore National Laboratory, Livermore, CA
• Marilyn Stovall, Ph.D., Melissa Bondy, Ph.D., Margaret Spitz, M.D., M.P.H., University of Texas M. D. Anderson Cancer Center, Houston, TX
• Bruce Alexander, Ph.D., Leslie Robison, Ph.D, University of Minnesota, Minneapolis, MN