Evidence From Humans
 
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Genetic polymorphisms in the apoptosis-associated genes FAS and FASL and breast cancer risk
Crew, K. D., Gammon, M. D., Terry, M. B., Zhang, F. F., Agrawal, M., Eng, S. M., Sagiv, S. K., Teitelbaum, S. L., Neugut, A. I., Santella, R. M. Carcinogenesis. 2007. 28:12, 2548-51.
Topic area
Environmental pollutant - PAHs Genetic variability
Study design
Population based case-control
Funding agency
NCI NIEHS Breast Cancer Research Foundation
Study Participants
Menopausal Status
The menopausal status of women included in this study is listed here.
No analysis based on 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 was 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 near time of diagnosis/reference. Samples with <15% inhibition were considered non-detect. FAS and FASL genotyped in mononuclear cells from w
Exposure assessment comment
PAH-DNA adducts reflect recent exposure. Blood obtained after diagnosis may not capture the relevant etiologic period. The relationship of PAH-DNA adducts to specific exposure sources is poorly understood, so this measure may not correctly rank the exposures relevant to disease. FAS and FAS ligand genes are involved in apoptotic signaling.
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.
Age, menopausal status, age at menarche, age at first pregnancy, parity, lactation history, oral contraceptive use, HRT use, smoking status, and alcohol use.
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
FAS1377 genotype, compared to homozygous wildtype GG, non-detectable PAH-DNA adducts:
Homozygous wildtype GG, detectable PAH-DNA adducts: aOR 1.21 (95% CI 0.96-1.53)
Variant GA or AA, detectable PAH-DNA adducts: aOR 1.36 (95% CI 1.01-1.83)
Variant GA or AA, detectable PAH-DNA adducts (4th quartile): aOR 1.60 (95% CI 1.00-2.57)

FAS670 genotype, compared to homozygous wildtype GG, non detectable PAH-DNA adducts:
Homozygous wildtype GG, detectable PAH-DNA adducts: aOR 1.18 (95% CI 0.78-1.77)
Variant GA, detectable PAH-DNA adducts: aOR 1.21 (95% CI 0.83-1.78)
Variant AA, detectable PAH-DNA adducts: aOR 1.36 (95% CI 0.89-2.07)
Variant GA, detectable PAH-DNA adducts (4th quartile): aOR 1.26 (95% CI 0.80-2.01)
Variant AA, detectable PAH-DNA adducts (4th quartile): aOR 1.77 (95% CI 0.99-3.15)
Results Comments
No association observed for FASL genotype, PAH-DNA adducts and breast cancer (data not shown). The interaction between detectable PAH-DNA adducts and FAS1377 was not significant on the multiplicative scale (p for interaction = 0.20). The authors note that it is possible that the genotypes evaluated are related to breast cancer risk in an older population.
Author address
Department of Medicine and the Herbert Irving Comprehensive Cancer Center, Columbia University, 161 Fort Washington Avenue, 10-1072, New York, NY 10032, USA. kd59@columbia.edu
Controls participation rate
63% completed interview 46% both completed intervi
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