Environment and Breast Cancer: Science Review
About
Xeroderma pigmentosum complementation group C genotypes/diplotypes play no independent or interaction role with polycyclic aromatic hydrocarbons-DNA adducts for breast cancer risk
Shen, J., Gammon, M. D., Terry, M. B., Teitelbaum, S. L., Eng, S. M., Neugut, A. I., Santella, R. M. Eur J Cancer. 2008. 44:5, 710-7.
Topic area
Environmental pollutant - PAHs Genetic variants
Environmental pollutant - PAHs Genetic variants
Study design
Population based case-control
Population based case-control
Funding agency
NCI NIEHS Breast Cancer Research Fund
NCI NIEHS Breast Cancer Research Fund
Study Participants
Number of Cases
873
873
Menopausal Status
The menopausal status of women included in this study is listed here.
No analyses based on menopausal status
Number of Controls
Controls: 941
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.
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.
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. XPC genotyped in mononuclear cell
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. XPC genotyped in mononuclear cell
How exposure was measured
Biological Questionnaire, in person
Biological Questionnaire, in person
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. Treatment status of cases not specified, but in overall LIBCSP, serum obtained from 77% of cases prior to chemotherapy initiation. The XPC protein is involved in the recognition of bulky DNA adducts.
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. Treatment status of cases not specified, but in overall LIBCSP, serum obtained from 77% of cases prior to chemotherapy initiation. The XPC protein is involved in the recognition of bulky DNA adducts.
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 at menarche, parity, lactation, months of lactation, age at first birth, number of miscarriages, history of fertility problems, alcohol use, race, education, religion, marital status, age at reference, and smoking status.
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
XPC Ala499Val genotype, compared to homozygous wildtype CC, non-detectable PAH-DNA adducts:
Homozygous wildtype CC, detectable PAH-DNA adducts: OR 1.3 (95% CI 1.0-1.8)
Homozygous wildtype CC, detectable ≥ median: OR 1.5 (95% CI 1.1-2.0)
Variant CT or TT, detectable PAH-DNA adducts: OR 1.3 (95% CI 0.9-1.7)
Variant CT or TT, detectable < median: OR 1.6 (95% CI 1.1-2.2)
XPC Lys939Gln genotype, compared to homozygous wildtype AA, non-detectable PAH-DNA adducts:
Homozygous wildtype AA, detectable PAH-DNA adducts: OR 1.5 (95% CI 1.0-2.1)
Variant AC or CC, detectable PAH-DNA adducts: OR 1.5 (95% CI 1.1-2.0)
Variant AC or CC, detectable < median: OR 1.5 (95% CI 1.0-2.1)
Variant AC or CC, detectable ≥ median: OR 1.5 (95% CI 1.0-2.1)
XPC diplotype, compared to call other diplotypes, non-detectable PAH-DNA adducts:
CC-CC, detectable < median: OR 1.7 (95% CI 1.1-2.5)
All other diplotypes, detectable PAH-DNA adducts: OR 1.3 (95% CI 1.0-1.6)
CC-CC, detectable PAH-DNA adducts: OR 1.6 (95% CI 1.1-2.2)
CC-CC, detectable < median: OR 1.7 (95% CI 1.1-2.5)
XPC Ala499Val genotype, compared to homozygous wildtype CC, non-detectable PAH-DNA adducts:
Homozygous wildtype CC, detectable PAH-DNA adducts: OR 1.3 (95% CI 1.0-1.8)
Homozygous wildtype CC, detectable ≥ median: OR 1.5 (95% CI 1.1-2.0)
Variant CT or TT, detectable PAH-DNA adducts: OR 1.3 (95% CI 0.9-1.7)
Variant CT or TT, detectable < median: OR 1.6 (95% CI 1.1-2.2)
XPC Lys939Gln genotype, compared to homozygous wildtype AA, non-detectable PAH-DNA adducts:
Homozygous wildtype AA, detectable PAH-DNA adducts: OR 1.5 (95% CI 1.0-2.1)
Variant AC or CC, detectable PAH-DNA adducts: OR 1.5 (95% CI 1.1-2.0)
Variant AC or CC, detectable < median: OR 1.5 (95% CI 1.0-2.1)
Variant AC or CC, detectable ≥ median: OR 1.5 (95% CI 1.0-2.1)
XPC diplotype, compared to call other diplotypes, non-detectable PAH-DNA adducts:
CC-CC, detectable < median: OR 1.7 (95% CI 1.1-2.5)
All other diplotypes, detectable PAH-DNA adducts: OR 1.3 (95% CI 1.0-1.6)
CC-CC, detectable PAH-DNA adducts: OR 1.6 (95% CI 1.1-2.2)
CC-CC, detectable < median: OR 1.7 (95% CI 1.1-2.5)
Results Comments
A significant association between the XPC CC-CC diplotype and breast cancer risk was observed, independent of PAH-DNA adducts. The interaction between detectable PAH-DNA adducts and CC-CC diplotype was not significant (multiplicative p for interaction = 0.69). No significant evidence for interactions with PAH-DNA adducts when XPC Ala499Val C/T and XPC Lys939Gln A/C genotypes were considered separately.
A significant association between the XPC CC-CC diplotype and breast cancer risk was observed, independent of PAH-DNA adducts. The interaction between detectable PAH-DNA adducts and CC-CC diplotype was not significant (multiplicative p for interaction = 0.69). No significant evidence for interactions with PAH-DNA adducts when XPC Ala499Val C/T and XPC Lys939Gln A/C genotypes were considered separately.
Author address
Department of Environmental Health Sciences, Mailman School of Public Health, Columbia University, 630 West 168th Street, P&S 19-418, New York, NY 10032, USA. js2182@columbia.edu
Department of Environmental Health Sciences, Mailman School of Public Health, Columbia University, 630 West 168th Street, P&S 19-418, New York, NY 10032, USA. js2182@columbia.edu
Controls participation rate
63% completed interview 46% both completed intervi
63% completed interview 46% both completed intervi