Evidence From Humans
 
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IGHMBP2 Thr671Ala polymorphism might be a modifier for the effects of cigarette smoking and PAH-DNA adducts to breast cancer risk
Shen, J., Beth Terry, M., Gammon, M. D., Gaudet, M. M., Teitelbaum, S. L., Eng, S. M., Sagiv, S. K., Neugut, A. I., Santella, R. M. Breast Cancer Res Treat. 2006. 99:1, 1-7.
Topic area
Environmental pollutant - PAHs Genetic variants
Study design
Population based case-control
Funding agency
NCI NIEHS Breast Cancer Research Fund
Study Participants
Menopausal Status
The menopausal status of women included in this study is listed here.
Analyses stratified by menopausal status
Number of Controls
Controls: 941
Participant selection: Inclusion and exclusion criteria
Criteria used to select participants in the study.
Female residents of Nassau and Suffolk Counties (Long Island), NY, participating in the Long Island Breast Cancer Study Project, age 20 or older, English-speaking, newly diagnosed with in situ or invasive breast cancer in 1996-1997. Cases identified by regional hospital pathology laboratories. Controls had no breast cancer history and were matched by 5-year age group, identified by random-digit-dialing or Medicare records (for women 65 and older). The analyses reported here were limited to women for whom PAH-DNA adducts were assessed in blood samples, which is reflected in the number of cases/controls reported above. Participants for whom samples could not be genotyped (<10%), generally due to insufficient DNA, were also excluded.
Comment about participation selection
In the LIBCSP, giving a blood sample was positively associated with being white, ever using alcohol, ever using HRT, ever having a mammography, and lactation history. Older women and former smokers were less likely to give blood. Blood donation was not associated with case-control status, so these differences between the total study population and the sub-population who donated blood should not bias the findings, but could affect generalizability. Treatment status of cases not specified, but in overall LIBCSP, serum obtained from 77% of cases prior to chemotherapy initiation.
Exposure Investigated
Exposures investigated
PAH-DNA adducts were measured by competitive enzyme linked immunosorbent assay (ELISA) in blood samples obtained an average of 3 months after diagnosis for cases. Samples with <15% inhibition were considered non-detect. IGHMBP2-67 genotyped in mononucle
How exposure was measured
Biological Questionnaire, in person
Exposure assessment comment
PAH-DNA adducts reflect recent exposure. The relationship of PAH-DNA adducts to specific exposure sources is poorly understood. The protein IGHMBP2 may be involved in DNA repair, replication, and recombination.
Breast cancer outcome investigated
Primary incident breast cancer
DCIS/LCIS
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, ever lactated, months of lactation, age at first birth, number of miscarriages, history of fertility problems, race, education, religion, marital status, menopausal status and family history
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
IGHMBP2 Thr671Ala genotype, compared to homozygous wildtype AA, non-detectable PAH-DNA adducts:
Homozygous wildtype AA, detectable PAH-DNA adducts: OR 1.2 (95% CI 0.9-1.6)
Homozygous wildtype AA, detectable < median: OR 1.2 (95% CI 0.9-1.8)
Homozygous wildtype AA, detectable ≥ median: OR 1.1 (95% CI 0.8-1.6)
Variant AG or GG, detectable PAH-DNA adducts: OR 1.4 (95% CI 1.0-1.8)
Variant AG or GG, detectable < median: OR 1.4 (95% CI 1.0-1.9)
Variant AG or GG, detectable ≥ median: OR 1.3 (95% CI 1.0-1.9)
Results Comments
The interaction between IGHMPB2-671 variant alleles and detectable PAH-DNA adducts was not significant (multiplicative p for interaction = 0.80).
Author address
Department of Environmental Health Sciences, Mailman School of Public Health, Columbia University, New York, NY, USA. js2182@columbia.edu
Controls participation rate
63% completed interview 46% both completed intervi
Reviewers Comments
The authors state the selection of IGHMBP2-671 SNP in the study was based on a biological prediction that may be inaccurate, and there may be other polymorphisms associated with breast cancer that could also play a role.
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