Evidence From Humans
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Acrylamide exposure and incidence of breast cancer among postmenopausal women in the Danish Diet, Cancer and Health Study
Olesen, P. T., Olsen, A., Frandsen, H., Frederiksen, K., Overvad, K., Tjonneland, A. Int J Cancer. 2008. 122:9, 2094-100.
Topic area
Environmental pollutant - Acrylamide
Study design
Prospective cohort; Nested case-control
Funding agency
European Commission Research Directorate-General N
Study Participants
Menopausal Status
The menopausal status of women included in this study is listed here.
Analysis restricted to postmenopausal women
Number of Controls
Controls: 374
Participant selection: Inclusion and exclusion criteria
Criteria used to select participants in the study.
29,875 women living in greater Copenhagen and Aarhus were enrolled in the Danish Diet, Cancer and Health study cohort between December 1993 and May 1997. Eligible women were between the ages of 50 and 64 years, born in Denmark, and not registered with a previous diagnosis of cancer in the Danish Cancer Registry. This analysis was restricted to postmenopausal women; women without HRT use who reported at least one menstruation no more than twelve months before entry were considered premenopausal, and so were excluded. Forty-five women were excluded due to missing data about menopausal status. 434 incident breast cancer cases were identified through linkage to the Danish Breast Cancer Cooperative Group registry through 2000. One control per case was selected from among women who were cancer-free at the exact age at diagnosis of a paired case, matched on age at inclusion into the cohort (+/- 1/2 years), certainty of postmenopausal status, and use of HRT at inclusion into the cohort. Sixty case-control pairs were excluded because of lack of or problems with blood samples and/or missing information on potential confounders.
Comment about participation selection
Follow-up through linkage to the Danish Cancer Registry was complete for 99.8% of women in the cohort. 13.8 percent of case-control pairs were excluded due to lack of blood samples available for adduct analyses or missing information about confounding variables. The authors did not specify whether more data were missing from case or control groups.
Exposure Investigated
Exposures investigated
Acrylamide-hemoglobin adducts (AA-Hb) and glycidamide-hemoglobin adducts (GA-Hb) measured in fasting blood samples collected at enrollment.
Exposure assessment comment
Glycidamide is the mutagenic metabolite of acrylamide, and glycidamide DNA adducts are considered a biomarker for the genotoxic dose reflecting the individual ability to metabolically activate acrylamide. Hemoglobin adducts represent recent exposure (~past 4 months) and are not source-specific. Exposure sources of acrylamide other than smoking were not determined. Other sources include foods cooked at high heat and industrial occupational exposures.
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.
Parity, age at first birth, length of school education, duration of HRT use, BMI, alcohol intake, smoking.
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
Overall breast cancer:
Per 10x increase in AA-Hb (pmol/g): aIRR 1.9 (95% CI 0.9-4.0)
Per 10x increase in GA-Hb (pmol/g): aIRR 1.3 (95% CI 0.6-2.8)

ER+ breast cancer:
Per 10x increase in AA-Hb (pmol/g): aIRR 2.7 (95% CI 1.1-6.6)
Per 10x increase in GA-Hb (pmol/g): aIRR 1.5 (95% CI 0.6-3.8)
Results Comments
Adduct levels were about three times higher in smokers than non-smokers. Associations tended to be higher in smokers than non-smokers in stratified analyses, but none of the differences were statistically significant. Authors also considered models with mutual adjustment of AA-Hb and GA-Hb, which tended to reduce effect estimates for GA-Hb.
Author address
National Food Institute, Technical University of Denmark, Soborg, Denmark. petol@food.dtu.dk
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