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National Institute of Environmental Health Sciences

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Your Environment. Your Health.

Publication Detail

Title: Polymorphisms in nucleotide excision repair genes, polycyclic aromatic hydrocarbon-DNA adducts, and breast cancer risk.

Authors: Crew, Katherine D; Gammon, Marilie D; Terry, Mary Beth; Zhang, Fang Fang; Zablotska, Lydia B; Agrawal, Meenakshi; Shen, Jing; Long, Chang-Min; Eng, Sybil M; Sagiv, Sharon K; Teitelbaum, Susan L; Neugut, Alfred I; Santella, Regina M

Published In Cancer Epidemiol Biomarkers Prev, (2007 Oct)

Abstract: Genes involved in the nucleotide excision repair (NER) pathway, which removes bulky DNA adducts, are potential low-penetrance cancer susceptibility genes. We recently reported an association between detectable polycyclic aromatic hydrocarbon (PAH)-DNA adducts and breast cancer risk. Using a population-based breast cancer case-control study on Long Island, New York, we examined whether polymorphisms in NER genes modified the association between PAH-DNA adducts and breast cancer risk. We examined polymorphisms in ERCC1 (3'-untranslated region 8092C/A), XPA (5'-untranslated region -4G/A), XPD (Asp(312)Asn in exon 10), XPF (Arg(415)Gln in exon 8), and XPG (Asp(1104)His in exon 15) in 1,053 breast cancer cases and 1,102 population-based controls. The presence of at least one variant allele in XPD was associated with a 25% increase in the odds ratio [OR, 1.25; 95% confidence interval (95% CI), 1.04-1.50] for breast cancer. The increase associated with homozygosity of the variant alleles for XPD and ERCC1 was stronger among those with detectable PAH-DNA adduct levels (OR, 1.83; 95% CI, 1.22-2.76 and OR, 1.92; 95% CI, 1.14-3.25 for detectable versus nondetectable adducts and homozygous wild-type genotype for XPD and ERCC1, respectively). We found no association between XPA, XPF, and XPG genotypes, PAH-DNA adducts, and breast cancer risk. When we combined genotypes for these NER pathway genes, there was a significant trend for increasing breast cancer risk with increasing number of putative high-risk alleles. Overall, this study suggests that the risk of breast cancer may be elevated among women with polymorphisms in NER pathway genes and detectable PAH-DNA adducts.

PubMed ID: 17932351 Exiting the NIEHS site

MeSH Terms: Adult; Aged; Alleles; Breast Neoplasms/genetics*; Case-Control Studies; DNA Adducts/genetics*; DNA Repair/genetics*; DNA-Binding Proteins/genetics; Endonucleases/genetics; Exons/genetics; Female; Genetic Predisposition to Disease; Genotype; Homozygote; Humans; Middle Aged; New York; Odds Ratio; Polycyclic Aromatic Hydrocarbons; Polymorphism, Genetic/genetics*; Risk Factors; Xeroderma Pigmentosum Group A Protein/genetics; Xeroderma Pigmentosum Group D Protein/genetics

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