Evidence From Humans
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Polymorphisms in XRCC1 modify the association between polycyclic aromatic hydrocarbon-DNA adducts, cigarette smoking, dietary antioxidants, and breast cancer risk
Shen, J., Gammon, M. D., Terry, M. B., Wang, L., Wang, Q., Zhang, F., Teitelbaum, S. L., Eng, S. M., Sagiv, S. K., Gaudet, M. M., Neugut, A. I., Santella, R. M. Cancer Epidemiol Biomarkers Prev. 2005. 14:2, 336-42.
Topic area
Genetic variability
Study design
Population based cased-control
Funding agency
US Congress, NCI, NIEHS
Study Participants
Menopausal Status
The menopausal status of women included in this study is listed here.
Pre menopausal
Post menopausal
Number of Controls
Controls: 1,110
Participant selection: Inclusion and exclusion criteria
Criteria used to select participants in the study.
Population-based participants in the Long Island Breast Cancer Study Project
Exposures investigated
PAH-DNA adducts in serum
Statistical Analysis
Ethnic groups with separate analysis
If this study provided a separate analysis by ethnic or racial group, the groups are listed here.
White, nonwhite
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.
Adequately controlled
Genetic characterization included
If the study analyzed relationships between environmental factors and inherited genetic variations, this field will be marked “Yes.” “No”, if not.
Description of major analysis
Logistic regression
Strength of associations reported
Breast cancer risk was not substantially elevated in relation to genotypes for XRCC1 codon 194 or 399. 399 Gln carriers showed nonsignificantly higher risk in premenopausal women.
No evidence of interaction with PAH-DNA adducts for codon194; Codon 399 increased risk among subjects with both detectable PAH-DNA adducts and 399Gln allele: OR= 1.33; 95% CI 0.98-1.84), though the interaction was not statistically significant. 399Gln carriers who were never smokers OR=1.31; 95% (1.01-1.69) compared to Arg/Arg genotype multiplicative interaction term P = 0.03.
Breast cancer risk for 399Gln allele and detectable adducts vs. neither among never-smoking women OR 1.92; 95% CI 1.21-3.07, though the multiplicative interation term is nonsignificant
Fruits and vegetables were protective
Results Comments
"X-ray repair cross complementing group 1 (XRCC1) protein is involved in the base-excision repair pathway and plays a critical role in repairing DNA base damage and DNA single-strand breaks. Two common single nucleaotide polymorphisms: Arg194Trp, Arg399Gln "Suggestive weak additive interaction between the XRCC1 399Gln allele and PAH-DNA adducts on breast cancer risk, only among never smokers"
Author address
Department of Environmental Health Sciences, Mailman School of Public Health, Columbia University, New York, NY 10032, USA. js2182@columbia.edu
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