Xeroderma pigmentosum complementation group C genotypes/diplotypes play no independent or interaction role with polycyclic aromatic hydrocarbons-DNA adducts for breast cancer risk.
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.
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
Jing
J
Shen
Marilie D
MD
Gammon
Mary Beth
MB
Terry
Susan L
SL
Teitelbaum
Sybil M
SM
Eng
Alfred I
AI
Neugut
Regina M
RM
Santella
D000368:Aged; D001943:Breast Neoplasms / Q000235:genetics*; D016022:Case-Control Studies; D018736:DNA Adducts / Q000235:genetics*; D004268:DNA-Binding Proteins / Q000235:genetics*; D005260:Female; D005838:Genotype; D006801:Humans; D011084:Polycyclic Aromatic Hydrocarbons; D011110:Polymorphism, Genetic / Q000235:genetics*; D012307:Risk Factors; D012907:Smoking / Q000009:adverse effects
D018736:DNA Adducts; D004268:DNA-Binding Proteins; D011084:Polycyclic Aromatic Hydrocarbons; C095911:polycyclic aromatic hydrocarbons-DNA adduct; C086984:XPC protein, human