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Polymorphisms in phase I and phase II genes and breast cancer risk and relations to persistent organic pollutant exposure: a case-control study in Inuit women
Ghisari, M., Eiberg, H., Long, M., Bonefeld-Jorgensen, E. C. Environ Health. 2014. 13:1, 19.
Topic area
Environmental pollutant - PFCs PCBs Organochlorine pesticides Genetic variab
Study design
Population based case-control
Funding agency
International Polar Year Committee Commission for
Study Participants
Menopausal Status
The menopausal status of women included in this study is listed here.
No analyses based on menopausal status
Number of Controls
Controls: 115
Participant selection: Inclusion and exclusion criteria
Criteria used to select participants in the study.
Cases were women of Greenland Inuit descent (more than two grandparents born in Greenland), who were in the breast cancer registry at a hospital in Greenland, where all breast cancer cases are registered in the country. Controls were also women of Greenland Inuit descent, who participated in another study of POP measurements, or they were in the Artic Monitoring Assessment Programme. The controls were matched to the cases based on age (4 year intervals), and frequency matched with cases based on districts. The sampling period was from 2000-2003.
Comment about participation selection
Including controls from two other monitoring studies may have led to selection bias, despite matching. The authors do not state the selection criteria that was applied to the controls in the two other studies.
Exposure Investigated
Exposures investigated
Serum samples collected before treatment and measured: 8 OCPs: DDT, DDE, HCH, aldrin, HCB, oxychlordane, cis-nonachlor, trans-nonachlor 10 PFCs: PFHpA, PFOA, PFNA, PFDA, PFUnA, PFDoA, PFTrA, PFHxS, PFOS, PFOSA 5 metals: selenium, zinc, lead, mercury, cadm
Exposure assessment comment
CYP & COMT genes are involved in xenobiotic metabolism and/or in estrogen biosynthesis and metabolism. p-values for PFAS x polymorphism product-terms were not significant.
Breast cancer outcome investigated
Primary incident breast cancer
Ethnic groups with separate analysis
If this study provided a separate analysis by ethnic or racial group, the groups are listed here.
Inuit descent
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.
Age and cotinine
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, polymorphisms in CYP (CYP1A1, CYP1B1, CYP17,
Strength of associations reported
Among those with at least one variant allele:
High vs low PFOS:
CYP1A1 OR 1.21 (95% CI 1.29-115)
COMT OR 16.8 (95% CI 1.68-167)
CYP17 OR 18.2 (95% CI 1.67-199)
High vs low PFOA:
CYP1A1 OR 3.58 (95% CI 0.81-15.8)
COMT OR 3.73 (95% CI 0.86-16.3)
CYP17 OR 8.79 (95% CI 1.22-63.5)

No associations between sum PCBs and breast cancer risk were identified in participants with polymorphisms at the CYP1A, CYP1B, COMT, CYP17A1, CYP19A1, and BRCA1 loci.
Results Comments
Very small sample size for evaluating gene-environment interactions (analyses presented here based on 18-26 cases). Assessment of interaction between polymorphisms and PFOS and PFOA was not performed for CYP19_CT, CYP19_TTA or CYP1B1 because too few cases/controls with high exposure and variant allele.
Author address
Centre for Arctic Health & Unit of Cellular and Molecular Toxicology, Department of Public Health, Aarhus University, Bartholins Alle 2, Build 1260, 8000 Aarhus C, Denmark. ebj@mil.au.dk.
Reviewers Comments
The Arctic Inuit population has one of the highest burden of POPs globally. Greenland Inuit women have only started to see breast cancer increase since the 1970s.
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