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National Institute of Environmental Health Sciences

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Your Environment. Your Health.

Publication Detail

Title: Xeroderma pigmentosum complementation group C genotypes/diplotypes play no independent or interaction role with polycyclic aromatic hydrocarbons-DNA adducts for breast cancer risk.

Authors: Shen, Jing; Gammon, Marilie D; Terry, Mary Beth; Teitelbaum, Susan L; Eng, Sybil M; Neugut, Alfred I; Santella, Regina M

Published In Eur J Cancer, (2008 Mar)

Abstract: Xeroderma pigmentosum complementation group C (XPC) is an important DNA nuclear excision repair (NER) gene that recognises the damage caused by a variety of bulky DNA adducts. We evaluated the association of two common non-synonymous polymorphisms in XPC (Ala499Val and Lys939Gln) with breast cancer risk in the Long Island Breast Cancer Study Project (LIBCSP), a population-based case-control study. Genotyping of 1067 cases and 1110 controls was performed by a high throughput assay with fluorescence polarisation. There were no overall associations between XPC polymorphisms and breast cancer risk. A diplotype CC-CC was significantly associated with increased breast cancer risk compared with diplotype CA-CA (OR=1.4, 95%CI: 1.0-1.9), but was not significant when compared with all other diplotypes combined (OR=1.22, 95%CI: 0.97-1.53). No modification effects were observed for XPC genotypes by cigarette smoking status, smoking pack-years or polycyclic aromatic hydrocarbons (PAH)-DNA adducts. The increase in breast cancer risk was slightly more pronounced among women with detectable PAH-DNA adducts and carrying the diplotype CC-CC (OR=1.6, 95%CI: 1.1-2.2) compared to women with non-detectable PAH-DNA adducts carrying other diplotypes combined, but no statistically significant interaction was observed (P(interaction)=0.69). These data suggest that XPCs have neither independent effects nor interactions with cigarette smoking and PAH-DNA adducts for breast cancer risk. Further studies with multiple genetic polymorphisms in NER pathway are warranted.

PubMed ID: 18053706 Exiting the NIEHS site

MeSH Terms: Aged; Breast Neoplasms/genetics*; Case-Control Studies; DNA Adducts/genetics*; DNA-Binding Proteins/genetics*; Female; Genotype; Humans; Polycyclic Aromatic Hydrocarbons; Polymorphism, Genetic/genetics*; Risk Factors; Smoking/adverse effects

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