Evidence From Humans
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Bulky DNA adducts and breast cancer risk in the prospective EPIC-Italy study
Saieva, C., Peluso, M., Masala, G., Munnia, A., Ceroti, M., Piro, S., Sera, F., Bendinelli, B., Pala, V., Sieri, S., Tumino, R., Giurdanella, M. C., Panico, S., Mattiello, A., Vineis, P., Polidoro, S., Matullo, G., Palli, D. Breast Cancer Res Treat. 2011. 129:2, 477-84.
Topic area
Environmental pollutant - PAHs
Study design
Prospective cohort; Nested case-control
Study Participants
Menopausal Status
The menopausal status of women included in this study is listed here.
No analyses by menopausal status
Number of Controls
Controls: 292
Participant selection: Inclusion and exclusion criteria
Criteria used to select participants in the study.
Women from the Italian cohort of the European Prospective Investigation into Cancer and nutrition (EPIC) were included in this study. The Italian cohort includes 47,749 individuals, of which 32,578 are women aged 35-64 years, from 5 regions of Italy, who were enrolled between January 1993-March 1998 and followed through December 2001. Cases and controls were selected from women who did not use exogenous hormones for contraception and did not have a previous cancer diagnosis at the time of blood donation. Cases were identified by linkage to local cancer registries and hospital medical records. Controls were selected from among women alive and free of cancer -- other than non-melanoma skin cancer -- at that time of the case diagnosis (risk set sampling), with matching to cases on study center, age at blood donation and menopausal status. Three matched case-control sets were excluded because samples were not available for DNA analysis.
Exposure Investigated
Exposures investigated
Bulky DNA adducts were measured using 32P-postlabelling on peripheral leukocyte (white blood cell) DNA.
Exposure assessment comment
The authors note that the 32P-postlabeling method has a high sensitivity for bulky DNA adducts typically formed by aromatic compounds, but does not identify PAH adducts specifically. The method does not link DNA adducts to exposure sources. The DNA adduct levels were verified using 20% of DNA samples with a second measurement, and the results were in 98% agreement. DNA adducts reflect recent exposure. Adduct measures in blood obtained after before diagnosis may capture a relevant exposure period affecting breast cancer risk, though it would appear follow-up period was relatively short (~3 years) for some women (distribution of follow-up time not specified).
Breast cancer outcome investigated
Primary incident breast cancer
Confounders considered
Other breast cancer risk factors, such as family history, age at first birth, and hormone replacement therapy use, that were taken into account in the study.
BMI, smoking habits, education level, age and menarche, age at first delivery, alcohol consumption
Genetic characterization included
If the study analyzed relationships between environmental factors and inherited genetic variations, this field will be marked “Yes.” “No”, if not.
Strength of associations reported
DNA adducts detected versus not detected:
OR 1.14 (95% CI 0.67-1.93)

There was no significant difference in adduct levels between cases and controls.
Results Comments
Other models (continuous, above/below median, and tertile) did not show significant associations between adduct levels and breast cancer risk. Authors report no significant results for analyses stratified by menopause or smoking status, but the data is not shown.
Author address
Molecular and Nutritional Epidemiology Unit, ISPO (Cancer Research and Prevention Institute), Ponte Nuovo, Via delle Oblate 2, 50139, Florence, Italy.
Reviewers Comments
These results are not consistent with other studies of DNA adducts and breast cancer, however it is important to note differences in study design including the use of bulky (rather than PAH-specific) DNA adducts to asses exposure in this study, and the lack of consideration of differences in susceptibility due to genetic variation (e.g. in genes related to PAH metabolism, DNA repair, etc.).
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