Variation in the detection, signaling, and repair of DNA damage contributes to human cancer risk. To assess capacity to modulate endogenous DNA damage among radiologic technologists who had been diagnosed with breast cancer and another malignancy (breast-other, n = 42), early-onset breast cancer (early-onset, age ≤35; n = 38), thyroid cancer (n = 68), long-lived cancer-free individuals (hyper-normals, n = 20) and cancer-free controls (n = 49) we quantified DNA damage (single strand breaks and abasic sites) in untreated lymphoblastoid cell lines using the alkaline comet assay. Komet™ software provided comet tail length, % DNA in tail (tail DNA), comet distributed moment (CDM), and Olive tail moment (OTM) summarized as the geometric mean of 100 cells. Category cut-points (median and 75th percentile) were determined from the distribution among controls. Tail length (for ≥75% versus below the median, age-adjusted) was most consistently associated with the highest odds ratios in the breast-other, early-onset, and thyroid cancer groups (with risk increased 10-, 5- or 19-fold, respectively, with wide confidence intervals) and decreased risk among the hyper-normal group. For the other three comet measures, risk of breast-other was elevated approximately three-fold. Risk of early-onset breast cancer was mixed and risk of thyroid cancer ranged from null to a two-fold increase. The hyper-normal group showed decreased odds ratios for tail DNA and OTM, but not CDM. DNA damage, as estimated by all comet measures, was relatively unaffected by survival time, reproductive factors, and prior radiation treatment. We detected a continuum of endogenous DNA damage that was highest among cancer cases, less in controls, and suggestively lowest in hyper-normal individuals. Measuring this DNA damage phenotype may contribute to the identification of susceptible sub-groups. Our observations require replication in a prospective study with a large number of pre-diagnostic samples.
|Original language||English (US)|
|Number of pages||16|
|Journal||Mutation Research - Genetic Toxicology and Environmental Mutagenesis|
|State||Published - Oct 3 2005|
Bibliographical noteFunding Information:
This research was supported in part by contracts NO1-CP-15673, NO1-CP-51016, NO2-CP-81005, and NO2-CP-81121 by the National Cancer Institute, the National Institutes of Health, U.S. Public Health Service, Department of Health and Human Services and in part under the auspices of the U.S. Department of Energy by the University of California, Lawrence Livermore National Laboratory under Contract No. W-7405-Eng-48. The authors thank Dr. Thomas R. Fears for helpful advice on the coefficient of variation calculations. We are grateful to the radiologic technologists who participated in this study; Jerry Reid of the American Registry of Radiologic Technologists for continued support of this project; Diane Kampa of the University of Minnesota for overseeing data collection and coordination; Kathy Chimes of Westat, Inc. for data management; and Laura Bowen of Information Management Services, Inc. for biomedical computing.
- Comet assay
- Genetic variation
- Hyper-normal controls
- Multiple cancers
- Risk factors