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Adipose tissue PCB levels and CYP1B1 and COMT genotypes in relation to breast cancer risk in postmenopausal Danish women
Brauner, E. V., Loft, S., Wellejus, A., Autrup, H., Tjonneland, A., Raaschou-Nielsen, O. Int J Environ Health Res. 2014. 24:3, 256-68.
Topic area
Environmental pollutant - PCBs
Study design
Prospective nested case-control
Funding agency
Danish Medical Research Council Danish Cancer Soci
Study Participants
Menopausal Status
The menopausal status of women included in this study is listed here.
Analysis restricted to postmenopausal status
Number in Cohort
Controls: 409 Cohort: 24,697
Participant selection: Inclusion and exclusion criteria
Criteria used to select participants in the study.
Cancer-free women aged 50-64 years who were born in Denmark and living in Copenhagen or Aarhus were recruited between December 1993 and May 1997 as part of the Diet, Cancer, and Health cohort. Women were excluded according to the following criteria: cancer diagnosis before a visit to one of the study clinics; incomplete questionnaire; lifetime history of no menstruation; missing information on HRT; or a reported menstruation within 12 months before entering the cohort. For each case, a control was randomly selected among cohort members who were cancer-free at the age at diagnosis of the case, stratified on postmenopausal status, use of HRT at baseline, and age at baseline.
Comment about participation selection
All women in the study are postmenopausal.
Exposure Investigated
Exposures investigated
Buttock adipose tissue biopsy was collected at time of enrollment and analyzed for 18 PCB congeners in lipid, in the following groups: Potentially estrogenic: sum of PCBs 187 and 201. Anti-estrogenic, dioxin-like: sum of PCBs 118 and 156. Anti-estrogenic,
Exposure assessment comment
Adipose tissue samples were collected at baseline for every subject, prior to any reported breast cancer diagnosis.
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.
Education, BMI, alcohol consumption, number of childbirths, age at first delivery, duration of lactation, years of HRT use, history of benign tumor.
Genetic characterization included
If the study analyzed relationships between environmental factors and inherited genetic variations, this field will be marked Yes. No, if not.
Yes
Strength of associations reported
PCBs by grouping (μg/kg lipid), per doubling in concentration:
Σ potentially estrogenic PCBs: RR 0.96 (95% CI 0.71-1.30)
Σ potentially anti-estrogenic dioxin-like PCBs: RR 0.88 (95% CI 0.65-1.18)
Σ potentially anti-estrogenic limited dioxin-activity PCBs: RR 0.97 (95% CI 0.74-1.27)
Σ CYP inducing PCBs: RR 0.93 (95% CI 0.69-1.24)

Association between group 1B PCBs and allele variant with breast cancer risk:
CYP1B1
CC: RR 0.65 (95% CI 0.35-1.20)
CG: RR 1.01 (95% CI 0.68-1.51)
GG: RR 0.91 (95% CI 0.44-1.89)

Association between group 2A PCBs and allele variant with breast cancer risk:
CYP1B1
CC: RR 0.60 (95% CI 0.32-1.13)
CG: RR 1.05 (95% CI 0.69-1.59)
GG: RR 0.74 (95% CI 0.35-1.56)

Association between group 2B PCBs and allele variant with breast cancer risk:
CYP1B1
CC: RR 0.65 (95% CI 0.36-1.17)
CG: RR 1.08 (95% CI 0.74-1.57)
GG: RR 0.73 (95% CI 0.37-1.48)

Association between group 2B PCBs and allele variant with breast cancer risk:
CYPB1B
CC: RR 0.59 (95% CI 0.32-1.11)
CG: RR 1.05 (95% CI 0.70-1.57)
GG: RR 0.71 (95% CI 0.33-1.50)
Results Comments
No statistically significant interactions between CYP1B1 and COMT gene variations and PCB levels.
Author address
a Danish Building Research Institute, Construction and Health, Aalborg University , Copenhagen , Denmark .
Reviewers Comments
Authors note a limitation to this study is the lack of inclusion of PCB congeners 77, 126, and 169, which are more biologically potent and better representative of "potentially anti-estrogenic, dioxin-like congeners" than the group 2 PCBs investigated in this study. CYP1B1 and COMT produce enzymes that metabolize estrogen and PCBs. Some PCBs induce CYP1B1.
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