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National Cancer Institute U.S. National Institutes of Health www.cancer.gov
About DCEG

Peter D. Inskip, Sc.D.

Senior Investigator

Location: Executive Plaza South, Room 7052
Phone: 301-496-6600
Fax: 301-402-0207
E-mail: inskippe@mail.nih.gov

 Peter D. Inskip, Sc.D.

Biography

Dr. Inskip received a B.S. in biology from Yale College (1976), a M.S. in oceanography and limnology from the University of Wisconsin--Madison (1980) and a Sc.D. in epidemiology from the Harvard School of Public Health (1989). He joined NCI as a Fellow in 1989 and was appointed Staff Fellow in 1990 and Senior Staff Fellow in 1992. He left NCI in 1995 to accept a position as Associate Professor of Epidemiology in the College of Veterinary Medicine at Texas A&M University. He returned to NCI as an Investigator in 1998 and was appointed Senior Investigator in 2004. Dr. Inskip also serves as director of the Radiation Epidemiology Fellowship program. He was appointed Faculty Associate in Epidemiology at Johns Hopkins University in 2001. He serves on the steering committee of the Childhood Cancer Survivor Study, the Late Effects committee of the Children's Oncology Group, the Board of Epidemiology Advisors of the Central Brain Tumor Registry, the Commission on Cancer of the American College of Surgeons Brain/CNS Disease Site Team, and the advisory panel for the INTERPHONE Study, an international study of cellular telephones and cancer that is being coordinated by the International Agency for Research on Cancer.

Research Interests

  • Etiology of brain tumors in adults
  • Cancer risks attributable to medical exposures to ionizing radiation
  • Second cancers after childhood cancer
  • Multiple primary cancers

Research

Etiology of Brain Tumors

Brain cancer is among the most aggressive and deadly of cancers but also one of the most poorly understood. In response to public concerns about risks due to cellular telephones and other recently-introduced environmental exposures, and to pursue other leads concerning possible risk factors, I initiated a comprehensive case-control study of brain tumors in adults. This large, multi-faceted study includes patients newly-diagnosed with glioma, meningioma or acoustic neuroma at any of three hospitals in the U.S. The study design incorporated novel features for the evaluation of occupational exposures, including interviews tailored to individual work histories and provision for follow-up questioning, if necessary, after prompt review of occupational histories by an industrial hygienist. Because of the rapid ascertainment and enrollment of study participants, the proportion of proxy interviews for glioma cases was far lower than in previous case-control studies. Blood samples were collected for use in genetic, cellular and serological assays.

Our initial report concerned the possible effects of cellular telephones. We found no evidence of increased risk associated with recent use of cell phones for any of the three tumor types. In subsequent reports, we also did not observe associations of brain tumor risk with occupational exposure to magnetic fields nor with use of electrical appliances in the home. However, we confirmed and extended previous findings of an apparent reduced risk of glioma among persons with a history of allergies and other immune disorders, found a reduced risk of glioma among left-handed persons relative to right-handed persons, and described an association between season of birth and brain tumor risk. We also observed a reduced risk of glioma associated with early age at menarche or early age at first live birth. We found no overall association between glioma and occupational exposure to insecticides or herbicides; however, there was some indication of an elevated risk of meningioma in women with occupational exposure to herbicides. Detailed evaluations of risk in relation to occupational exposure to chlorinated solvents are in progress.

We are in the process of evaluating the relation between single nucleotide polymorphisms (SNPs) in a variety of genes and risk of brain tumors and are coordinating these efforts with those of other brain tumor investigators so that we might achieve sufficient sample sizes to address possible gene-environment and gene-gene interactions. To date we have evaluated brain tumor risk with respect to SNPs in genes in a variety of pathways, including xenobiotic metabolism, DNA repair, apoptosis and cell cycle control, oxidative stress, and insulin-like growth factors. To follow up on the allergy and autoimmune disease findings, we evaluated SNPs in a variety of cytokine genes and in an Illumina panel of innate immunity genes. With respect to possible gene-environment interaction, we demonstrated an increased risk of meningioma, but not glioma, associated with occupational exposure to lead, and showed that this association was stronger in persons with a variant allele in the gene for ALAD, an enzyme known to influence blood levels of lead. Studies in progress are moving away from the candidate gene approach to more agnostic, genetic marker analyses, such as those involving genome wide association studies. We also are pursuing opportunities to look at serum levels of immune factors in serum samples collected well in advance of brain cancer diagnosis and treatment.

Second Cancers after Childhood Cancer

I am collaborating with intramural and extramural investigators on studies of therapy-related new malignancies in five-year survivors of childhood cancer. To date, we have completed nested case-control studies of cancers of the brain, breast and thyroid gland within a cohort of 14,050 childhood cancer survivors (Childhood Cancer Survivor Study). The relative risk of second thyroid cancer was found to increase with increasing radiation dose for doses less than 20 Gy and decrease sharply at doses > 30 Gy, most probably due to radiation-related killing of thyroid tissue (Sigurdson et al., 2005; Ronckers et al. 2006). This is one of the first studies to demonstrate such an effect for solid cancers. No such downturn was apparent for meningioma or glioma, both of which demonstrated positive dose-response relations consistent with linearity (Neglia et al. 2006). The odds ratio for breast cancer increased linearly with radiation dose, reaching 11-fold for local breast doses in the range of 40 Gy relative to no radiation (P for trend < 0.0001) (Inskip et al., In press). Risk associated with breast irradiation was sharply reduced among women who received 5 Gy or more to the ovaries (P=0.002), most likely due to lessened exposure of radiation-damaged breast cells to stimulating effects of ovarian hormones. Radiation-related risk did not vary significantly by age at exposure. We currently are conducting studies of second bone and soft issue sarcoma, salivary gland cancer, and basal cell carcinoma of the skin. This study population is unique for its size, numbers of second cancers, and availability of radiotherapy and chemotherapy information data from the hospitals where the initial cancer was treated. Radiation treatment records are being used for detailed, site-specific radiation dosimetry that is being conducted by a medical physicist. Future analyses will address the possible importance of genetic polymorphisms as modifiers of therapy-related second cancer risks, and whether radiation-related cancers exhibit distinctive molecular characteristics at the molecular level.

Multiple Primary Cancers

I also use data collected through NCI's Surveillance, Epidemiology and End Results (SEER) program to study the occurrence of multiple primary cancers. Most recently, I used these data to evaluate the incidence of multiple primary cancers after childhood cancer and, separately, after a first cancer of the brain or central nervous system. We also used these data to assess variation over time in the ratio of site-specific cancer incidence in females relative to males.

Cancer in Chernobyl Clean-up Workers

The hundreds of thousands of men sent to Chernobyl after the reactor accident in 1986 provide a potential opportunity for learning about cancer risks due to protracted exposure to low-dose-rate radiation. I am collaborating with investigators from Estonia, Latvia, Lithuania and Finland on a study of cancer incidence among Chornobyl clean-up workers from Baltic countries that formerly were part of the Soviet Union. Studies to date indicate that radiation doses were lower than initially presumed and that direct health effects of the radiation exposure will be difficult to detect in epidemiologic studies. Although an excess of leukemia or other cancer attributable to radiation was not apparent in our initial analyses, clean-up workers did experience a high rate of suicide in comparison to the general population.

Keywords

brain cancer, brain tumors, multiple primary cancers, childhood cancer, cancer survivorship, Chernobyl, ionizing radiation, non-ionizing radiation, radiation

Selected Publications

Collaborators

DCEG Collaborators

  • Alina Brenner, Ph.D.; Rochelle Curtis, M.S.; Stephen Chanock M.D.; Ruth Kleinerman, M.S.; Martha Linet, M.D.; Preetha Rajaraman, M.S.; Cecile Ronckers, Ph.D.; Alice Sigurdson, Ph.D.; Patricia Stewart, Ph.D.; Nathaniel Rothman, M.D.; Mustafa Dosemeci, Ph.D.; Joseph Coble, Ph.D.; Kenneth Cantor, Ph.D.; Claudine Samanic, Ph.D.; Dilys Parry, Ph.D.; Regina Ziegler, Ph.D. ; Lene Veiga, Ph.D.; Sophia Wang, Ph.D.; Ruth Pfeiffer, Ph.D.; Rose Yang, Ph.D.; Parveen Bhatti, Ph.D.; Houda Boukheris, M.D.; Kiyo Mabuchi, Ph.D.

Other NCI Collaborators

  • Howard Fine, M.D.

Other Scientific Collaborators

  • Anssi Auvinen, M.D.; University of Tampere, Tampere, Finland
  • Peter Black, M.D.; Brigham and Women's Hospital, Boston, MA
  • John Boice, Jr., Sc.D.; International Epidemiology Institute; Rockville, MD
  • Mary Ann Butler, Ph.D.; NIOSH, Cincinnati, OH
  • Anneclaire De Roos, Ph.D.; Fred Hutchinson Cancer Research Center, Seattle, WA
  • Timo Hakulinen, Ph.D.; Finnish Cancer Registry, Helsinki, Finland
  • Elizabeth Hatch, Ph.D.; Boston University, Boston, MA
  • Roberta McKean-Cowdin, Ph.D.; University of Southern California, Los Angeles, CA
  • Anna Meadows, M.D., University of Pennsylvania School of Medicine, Philadelphia, PA
  • Ann Mertens, Ph.D.; Emory University, Atlanta, GA
  • Joseph Neglia, M.D.; University of Minnesota, Minneapolis, MN
  • Mati Rahu, Ph.D.; Institute of Clinical and Experimental Medicine, Tallinn, Estonia
  • Leslie Robison, Ph.D.; St. Jude Children's Research Hospital, Memphis, TN
  • Avima Ruder, Ph.D.; NIOSH Cincinnati, OH
  • Robert Selker, M.D.; Western Pennsylvania Hospital, Pittsburgh, PA
  • William Shapiro, M.D.; St. Joseph's Hospital and Medical Center, Phoenix, AZ
  • Aivars Stengrevics, M.D.; Latvian Oncological Centre, Riga, Latvia
  • Marilyn Stovall, Ph.D.; The University of Texas M. D. Anderson Cancer Center Houston, TX
  • Mare Tekkel, Ph.D.; Institute of Clinical and Experimental Medicine, Tallinn, Estonia

Professional Service

Advisory Committees

  • INTERPHONE Study Independent Scientific Oversight Committee (International Union Against Cancer), 2000 - present
  • Childhood Cancer Survivor Study (CCSS) Steering Committee, 2001 - present
  • Central Brain Tumor Registry of the United States (CBTRUS) Board of Advisors, 2002 - present
  • Children's Oncology Group (COG) Late Effects Steering Committee, January 2004 - present
  • Consultant/contributor; United Nations Scientific Committee on the Effects of Ionizing Radiation (UNSCEAR) 2005 Report to the General Assembly, 2005
  • Brain Tumor Progress Review Group (PRG) (National Cancer Institute/National Institute of Neurological Disorders and Stroke), July 5-7, 2000

Editorial Boards

  • Environmental Health Perspectives, February 2008 - present
  • Neuro-Oncology, January 2005 - December 2006

Awards

2005 NIH Group Merit Award: "For notable discoveries in quantifying dose-response patterns in radiation-related second malignancies among long-term survivors of childhood cancer".