Polymorphisms in XPC and ERCC2 genes, smoking and breast cancer risk
Article first published online: 14 JAN 2008
Copyright © 2008 Wiley-Liss, Inc.
International Journal of Cancer
Volume 122, Issue 9, pages 2101–2105, 1 May 2008
How to Cite
Shore, R. E., Zeleniuch-Jacquotte, A., Currie, D., Mohrenweiser, H., Afanasyeva, Y., Koenig, K. L., Arslan, A. A., Toniolo, P. and Wirgin, I. (2008), Polymorphisms in XPC and ERCC2 genes, smoking and breast cancer risk. Int. J. Cancer, 122: 2101–2105. doi: 10.1002/ijc.23361
- Issue published online: 25 FEB 2008
- Article first published online: 14 JAN 2008
- Manuscript Accepted: 8 NOV 2007
- Manuscript Received: 25 JUN 2007
- NIH. Grant Number: R01CA34588
- Komen Foundation. Grant Number: BCTR 2000 685
- Department of Defense. Grant Number: DAMD17-01-1-0578
- New York University Cancer Center. Grant Number: CA016087
- NIEHS Center. Grant Number: ES00260.
- breast cancer risk;
- XPC polymorphism;
- ERCC2 polymorphism;
- nucleotide excision repair
To evaluate the associations of breast cancer risk with polymorphisms in the XPC and XPD/ERCC2 DNA nucleotide excision repair genes, a case-control study nested within a prospective cohort of 14,274 women was conducted. Genotypes were characterized for 612 incident, invasive breast cancer cases and their 1:1 matched controls. The homozygous variant of a poly(AT) insertion/deletion polymorphism in intron 9 of the XPC gene (XPC-PAT+/+), was associated with breast cancer risk [odds ratio (OR) = 1.45, 95% confidence interval: 1.07–1.97], after adjustment for other breast cancer risk factors. The breast cancer risk associated with XPC-PAT+/+ did not differ by age at diagnosis. There was an indication of an interaction (p = 0.08) between the XPC-PAT+/+ genotype and cigarette smoking. Ever smokers with the XPC-PAT+/+ genotype were at elevated risk of breast cancer (OR = 1.56, CI: 0.95–2.58), but no differences were observed among never smokers. Analyses of the ERCC2 Lys751Gln polymorphism did not show an association with breast cancer risk, either overall or at younger ages. The results suggest that breast cancer risk is related to the XPC haplotype tagged by the XPC-PAT+/+ insertion-deletion polymorphism in intron 9. Further study of the XPC haplotypes and their interactions with smoking in relation to breast cancer risk is needed. © 2008 Wiley-Liss, Inc.