Polymorphisms in oxidative stress and inflammation pathway genes, low-dose ionizing radiation, and the risk of breast cancer among US radiologic technologists
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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.
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.
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.
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.
KeywordsPTGS2 COX-2 Inflammation Breast cancer Radiation
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.
- 1.Hall EJ, Giaccia AJ (2006) Radiobiology for the radiologist, 6th edn. Lippincott Williams & Wilkins, Philadelphia, p 88Google Scholar
- 13.National Research Council, Committee on the Biological Effects of Ionizing Radiations, BEIR VII (1990) Health risk from exposure to low levels of ionizing radiation. N.A. Press, Editor, WashingtonGoogle Scholar
- 14.United Nations Scientific Committee on the Effects of Atomic Radiation (2000) Sources and effects of ionizing radiation: UNSCEAR 2000 report to the general assembly, with scientific annexes. United Nations, New YorkGoogle Scholar
- 15.Land CE (1987) Temporal distributions of risk for radiation-induced cancers. J Chronic Dis 40(Suppl 2):45S–57SGoogle Scholar
- 24.Howe LR (2007) Inflammation and breast cancer. Cyclooxygenase/prostaglandin signaling and breast cancer. Breast Cancer Res 9:210Google Scholar
- 28.Facts and Figures (2002) Effect of AHS participation on cancer survival. Radiat Effects Res (Found Update) 13:28. Available from: http://www.rerf.or.jp/library/update/pdf/Spring2002.pdf