Polymorphisms in Nucleotide Excision Repair Genes are Associated with Increased Risk for Breast Cancer

Joel Schwartz, Ph.D.
Marilie D. Gammon, Ph.D.
University of North Carolina Chapel Hill and Regina Santella, Ph.D., Columbia University
NIEHS Grants U01CA/ES066572, P30ES009089, and P30ES010126

Genes responsible for nucleotide excision repair, the process that removes bulky DNA adducts, are thought to be cancer susceptibility genes. In a collaborative study, NIEHS grantees at the Columbia University Mailman School of Public Health and the University of North Carolina School public health investigated whether single nucleotide polymorphisms of nucleotide excision repair genes are associated with changes in the risk for breast cancer.

The researchers used a population-based breast cancer case-control study based on Long Island, New York. They examined polymorphisms in four nucleotide excision repair genes in over one thousand breast cancer cases and a similar number of control subjects. Study subjects with at least one variant allele in the gene XPD were found to have a 25 per cent greater risk for breast cancer. The risk was almost two times as high in subjects with detectable DNA adducts. Although the increases in risk are modest, they were statistically significant.

In summary, this study suggests that certain polymorphisms in nucleotide excision repair genes increase the risk of breast cancer in women. The risk is increased when DNA adducts are present. These results may improve the identification of high-risk individuals and preventable environmental risk factors for breast cancer.

Citation: Crew KD, Gammon MD, Terry MB, Zhang FF, Zablotska LB, Agrawal M, Shen J, Long CM, Eng SM, Sagiv SK, Teitelbaum SL, Neugut AI, Santella RM. Polymorphisms in nucleotide excision repair genes, polycyclic aromatic hydrocarbon-DNA adducts, and breast cancer risk. Cancer Epidemiol Biomarkers Prev. 2007 Oct;16(10):2033-41.