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.
Shen
Jing
J
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
Gammon
Marilie D
MD
Terry
Mary Beth
MB
Teitelbaum
Susan L
SL
Eng
Sybil M
SM
Neugut
Alfred I
AI
Santella
Regina M
RM
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