Journal Article

Reduced DNA repair of benzo[<i>a</i>]pyrene diol epoxide-induced adducts and common <i>XPD</i> polymorphisms in breast cancer patients

Qiuling Shi, Li-E. Wang, Melissa L. Bondy, Abenaa Brewster, S. Eva Singletary and Qingyi Wei

in Carcinogenesis

Volume 25, issue 9, pages 1695-1700
Published in print September 2004 | ISSN: 0143-3334
Published online September 2004 | e-ISSN: 1460-2180 | DOI: http://dx.doi.org/10.1093/carcin/bgh167
Reduced DNA repair of benzo[a]pyrene diol epoxide-induced adducts and common XPD polymorphisms in breast cancer patients

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Environmental chemicals are thought to play a role in the etiology of breast cancer, because polycyclic acromatic hydrocarbon (PAH)–DNA adducts are detectable in normal and malignant breast tissues. Peripheral blood lymphocytes (PBLs) from female breast cancer patients were more sensitive to in vitro exposure to benzo[a]pyrene diol epoxide (BPDE) than those from healthy controls. Therefore, we hypothesized that reduced DNA repair is associated with risk of breast cancer in women and the risk may be modulated by polymorphisms of DNA repair genes. In a case-control pilot study, we included 69 previously untreated female breast cancer patients and 79 controls frequency matched to the cases on age and ethnicity. The PBLs were used to measure DNA repair capacity (DRC) by using the host-cell reactivation (HCR) assay with a reporter gene damaged by exposure to 60 µM BPDE prior to transfection. We also genotyped for two common XPD polymorphisms Lys751Gln and Asp312Asn. We found that the mean DRC level was significantly lower in breast cancer patients (10.1%) than in controls (11.1%) (P = 0.008). Subjects with DRC lower than the median level of controls (11.0%) had >3-fold increased risk (OR = 3.36, 95% CI = 1.15–9.80) for breast cancer than did those with higher DRC after adjustment for age, smoking status and assay-related variables. None of the genotypes was statistically significantly associated with an increased risk of breast cancer, which may be due to the small number of observations in each subgroup. The XPD variant genotypes in general predicted the DRC better in the controls than in the cases, suggesting genetic variants of other DNA repair genes may be involved in these breast cancer patients. These findings suggest that women with reduced DRC may be at an increased risk of developing breast cancer. Large studies are warranted to confirm these preliminary findings.

Keywords: BPDE, benzo[a]pyrene diol epoxide; DRC, DNA repair capacity; HCR, host-cell reactivation; NER, nucleotide excision repair; PAH, polycyclic acromatic hydrocarbon; PBLs, peripheral blood lymphocytes

Journal Article.  5295 words.  Illustrated.

Subjects: Clinical Cytogenetics and Molecular Genetics

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