Polymorphisms in oxidative stress and inflammation pathway genes, low-dose ionizing radiation, and the risk of breast cancer among US radiologic technologists

Sara J. Schonfeld, Parveen Bhatti, Elizabeth E. Brown, Martha S. Linet, Steven L. Simon, Robert M. Weinstock, Amy A. Hutchinson, Marilyn Stovall, Dale L. Preston, Bruce H. Alexander, Michele M. Doody, Alice J. Sigurdson

Research output: Contribution to journalArticlepeer-review

26 Scopus citations

Abstract

Objective: Ionizing radiation, an established breast cancer risk factor, has been shown to induce oxidative damage and chronic inflammation. Polymorphic variation in oxidative stress and inflammatory-mediated pathway genes may modify radiation-related breast cancer risk. Methods: We estimated breast cancer risk for 28 common variants in 16 candidate genes involved in these pathways among 859 breast cancer cases and 1,083 controls nested within the US Radiologic Technologists cohort. We estimated associations between occupational and personal diagnostic radiation exposures with breast cancer by modeling the odds ratio (OR) as a linear function in logistic regression models and assessed heterogeneity of the dose-response across genotypes. Results: There was suggestive evidence of an interaction between the rs5277 variant in PTGS2 and radiation-related breast cancer risk. The excess OR (EOR)/Gy from occupational radiation exposure = 5.5 (95%CI 1.2-12.5) for the GG genotype versus EOR/Gy < 0 (95%CI < 0-3.8) and EOR/Gy < 0 (95%CI < 0-14.8) for the GC and CC genotypes, respectively, (p interaction = 0.04). The association between radiation and breast cancer was not modified by other SNPs examined. Conclusions: This study suggests that variation in PTGS2 may modify the breast cancer risk from occupational radiation exposure, but replication in other populations is needed to confirm this result.

Original languageEnglish (US)
Pages (from-to)1857-1866
Number of pages10
JournalCancer Causes and Control
Volume21
Issue number11
DOIs
StatePublished - Nov 2010

Bibliographical note

Funding Information:
Acknowledgments We are grateful to the radiologic technologists who participated in the USRT Study; Jerry Reid of the American Registry of Radiologic Technologists for continued support of this study; Diane Kampa and Allison Iwan of the University of Minnesota for data collection and study coordination; Laura Bowen of Information Management Systems for biomedical computing statistical support; and Chu-Ling Yu of the National Cancer Institute for editorial and scientific review. This research was supported by the Intramural Research Program of the National Cancer Institute, National Institutes of Health. This project has been funded in part with federal funds from the National Cancer Institute, National Institutes of Health, under Contract No. HHSN261200800001E. The content of this publication does not necessarily reflect the views or policies of the Department of Health and Human Services, nor does mention of trade names, commercial products, or organizations imply endorsement by the US Government.

Keywords

  • Breast cancer
  • COX-2
  • Inflammation
  • PTGS2
  • Radiation

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