Environment and Breast Cancer: Science Review
About
Genetic variation of TP53, polycyclic aromatic hydrocarbon-related exposures, and breast cancer risk among women on Long Island, New York
Gaudet, M. M., Gammon, M. D., Bensen, J. T., Sagiv, S. K., Shantakumar, S., Teitelbaum, S. L., Eng, S. M., Neugut, A. I., Santella, R. M. Breast Cancer Res Treat. 2008. 108:1, 93-9.
Topic area
Environmental pollutant - PAHs Genetic variability
Environmental pollutant - PAHs Genetic variability
Study design
Population based case-control
Population based case-control
Funding agency
NCI NIEHS NIOSH
NCI NIEHS NIOSH
Study Participants
Number of Cases
493
493
Menopausal Status
The menopausal status of women included in this study is listed here.
No analysis based on menopausal status
Number of Controls
Controls: 345
Controls: 345
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 was obtained from 77% of cases prior to chemotherapy initiation.
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 was 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. Smoking status was categorized as non-smoker, current smoker (within past 12 months), and f
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. Smoking status was categorized as non-smoker, current smoker (within past 12 months), and f
How exposure was measured
Biological Questionnaire, in person
Biological Questionnaire, in person
Exposure assessment comment
PAH-DNA adducts reflect recent (within months) exposures.
PAH-DNA adducts reflect recent (within months) exposures.
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.
Religion, alcohol use, cigarette smoking, oral contraceptive use, age at first child birth, and number of pregnancies
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
rs1042522 (Ex4 + 119 C > G; Arg72Pro) genotype, detectable PAH-DNA adducts:
Variant CG compared to homozygous wildtype CC: OR 1.25 (95% CI 0.88-1.77)
Variant GG compared to homozygous wildtype CC: OR 1.28 (95% CI 0.68-2.40)
rs17878362 (IVS3 16 bp deletion (DEL) > insertion (INS)), detectable PAH-DNA adducts:
DEL/INS compared to DEL/DEL: OR 0.97 (95% CI 0.67-1.42)
INS/INS compared to DEL/DEL: OR 1.73 (95% 0.53-5.64)
rs1625895 (IVS6 + 62 A > G) genotype, detectable PAH-DNA adducts:
Variant AG compared to homozygous wildtype AA: OR 0.97 (95% CI 0.66-1.43)
Variant GG compared to homozygous wildtype AA: OR 2.02 (95% CI 0.54-7.63)
rs1042522 (Ex4 + 119 C > G; Arg72Pro) genotype, detectable PAH-DNA adducts:
Variant CG compared to homozygous wildtype CC: OR 1.25 (95% CI 0.88-1.77)
Variant GG compared to homozygous wildtype CC: OR 1.28 (95% CI 0.68-2.40)
rs17878362 (IVS3 16 bp deletion (DEL) > insertion (INS)), detectable PAH-DNA adducts:
DEL/INS compared to DEL/DEL: OR 0.97 (95% CI 0.67-1.42)
INS/INS compared to DEL/DEL: OR 1.73 (95% 0.53-5.64)
rs1625895 (IVS6 + 62 A > G) genotype, detectable PAH-DNA adducts:
Variant AG compared to homozygous wildtype AA: OR 0.97 (95% CI 0.66-1.43)
Variant GG compared to homozygous wildtype AA: OR 2.02 (95% CI 0.54-7.63)
Results Comments
Associations between TP53 polymorphisms and breast cancer did not appear to differ among women with detectable PAH-DNA adducts compared to women with non-detectable PAH-DNA adducts (no formal test of interaction).
Associations between TP53 polymorphisms and breast cancer did not appear to differ among women with detectable PAH-DNA adducts compared to women with non-detectable PAH-DNA adducts (no formal test of interaction).
Author address
Department of Epidemiology, School of Public Health, University of North Carolina, Chapel Hill, NC, USA, gaudetm@mail.nih.gov
Department of Epidemiology, School of Public Health, University of North Carolina, Chapel Hill, NC, USA, gaudetm@mail.nih.gov
Controls participation rate
63% completed interview 46% both completed intervi
63% completed interview 46% both completed intervi
Reviewers Comments
This study does not explore a potential relationship between smoking status and PAH-DNA adduct levels.
This study does not explore a potential relationship between smoking status and PAH-DNA adduct levels.