Journal Article

Polymorphisms in nucleotide excision repair genes, smoking and breast cancer in African Americans and whites: a population-based case–control study

Leah E. Mechanic, Robert C. Millikan, Jon Player, Allan René de Cotret, Scott Winkel, Kendra Worley, Kristin Heard, Kimberley Heard, Chiu-Kit Tse and Temitope Keku

in Carcinogenesis

Volume 27, issue 7, pages 1377-1385
Published in print July 2006 | ISSN: 0143-3334
Published online January 2006 | e-ISSN: 1460-2180 | DOI: http://dx.doi.org/10.1093/carcin/bgi330

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Polymorphisms exist in several genes involved in nucleotide excision repair (NER), the principal pathway for removal of smoking-induced DNA damage. An epidemiologic study was conducted to determine whether these polymorphisms modify the association between smoking and breast cancer. DNA samples and exposure histories were analyzed as part of a large population-based case–control study of breast cancer in North Carolina. The study population included 2311 cases (894 African Americans, 1417 whites) and 2022 controls (788 African Americans, 1234 whites). Odds ratios (ORs) were calculated for breast cancer and smoking, and for breast cancer and nine non-synonymous coding polymorphisms in six NER genes (XPD codons 312 and 751, RAD23B codon 249, XPG codon 1104, XPC codon 939, XPF codons 415 and 662, and ERCC6 codons 1213 and 1230). Modification of ORs for smoking by single and combined NER genotypes was investigated. In this study population, smoking was more strongly associated with breast cancer in African American women compared with white women. Among African American women, the association of breast cancer and smoking was strongest among women with specific combinations of NER genotypes. Evidence for multiplicative interaction was found between combined NER genotypes and smoking dose (likelihood ratio test P = 0.06), duration (P = 0.09), time since cessation (P = 0.02), age at initiation (P = 0.04) and former smoking (P = 0.03). No interactions were observed in white women. Therefore, polymorphisms in NER genes may modify the relationship between breast cancer and smoking. These results are consistent with previous evidence of exposure-specific p53 mutations in breast tumors from current and former smokers, suggesting that smoking may play a role in breast cancer etiology.

Keywords: CBCS, Carolina Breast Cancer Study; CI, confidence interval; ETS, environmental tobacco smoke; LRT, likelihood ratio test; NER, nucleotide excision repair; nt, nucleotide; OR, odds ratio; rs, reference sequence number; SNP, single nucleotide polymorphism; TFIIH, transcription factor II H; XPC, Xeroderma Pigmentosum Group C

Journal Article.  8068 words. 

Subjects: Clinical Cytogenetics and Molecular Genetics

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