Evidence From Humans
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Pre-diagnostic acrylamide exposure and survival after breast cancer among postmenopausal Danish women
Olsen, A., Christensen, J., Outzen, M., Olesen, P. T., Frandsen, H., Overvad, K., Halkjaer, J. Toxicology. 2012. 296:1-3, 67-72.
Topic area
Environmental pollutant - Acrylamide
Study design
Prospective cohort; case-only
Funding agency
NordForsk The Danish Cancer Society Nordic Council
Study Participants
Menopausal Status
The menopausal status of women included in this study is listed here.
Analyses restricted to postmenopausal women
Number in Cohort
Cohort: 24,697
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 Cancer Registry through 2000, and cases were followed in the Danish Death Certificate Registry through 2008, for a median time of 10 years. Fourteen cases were excluded due to lack of a blood sample.
Comment about participation selection
Follow-up through linkage to the Danish Cancer Registry was complete for 99.8% of women in the cohort.
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. Samples were collected Multiple blood samples over the follow-up period might have helped better characterized exposure relevant to survival; blood samples were collected
Breast cancer outcome investigated
Primary breast cancer survival
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.
Smoking history, time between blood draw and diagnosis, alcohol, HRT use at blood sampling, BMI, education
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
Among non-smokers, per 25 pmol/g globin increase:

Mortality from breast cancer
AA-Hb: aHR 1.21 (95% CI 0.98-1.50)
GA-Hb: aHR 1.63 (95% CI 1.06-2.51)

Mortality from ER+ breast cancer
AA-Hb: aHR 1.31 (95% CI 1.02-1.69)
GA-Hb: aHR 2.23 (95% CI 1.38-3.61)

Among smokers, per 25 pmol/g globin increase:

Mortality from breast cancer
AA-Hb: aHR 0.95 (95% CI 0.79-1.13)
GA-Hb: aHR 1.20 (95% CI 0.86-1.68)

Mortality from ER+ breast cancer
AA-Hb: aHR 1.10 (95% CI 0.87-1.40)
GA-Hb: aHR 1.72 (95% CI 1.07-2.76)
Results Comments
'Non-smokers' at baseline included both never smokers and former smokers. This decision was made based on similar adduct levels in these groups. AA-Hb and GA-Hb levels were higher among smokers than non-smokers (for both cases and controls).
Author address
Danish Cancer Society Research Center, Danish Cancer Society, Copenhagen, Denmark. anja@cancer.dk
Reviewers Comments
Multiple blood samples over the follow-up period might have helped better characterize exposure relevant to survival.
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