This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Nock, N. L. Articles by Rybicki, B. A. Search for Related Content PubMed PubMed Citation Articles by Nock, N. L. Articles by Rybicki, B. A.

Associations between Smoking, Polymorphisms in Polycyclic Aromatic Hydrocarbon (PAH) Metabolism and Conjugation Genes and PAH-DNA Adducts in Prostate Tumors Differ by Race

¹ Department of Epidemiology and Biostatistics, Case Western Reserve University, Cleveland, Ohio; Departments of ² Environmental Health Sciences and ³ Epidemiology, Columbia University, Mailman School of Public Health, New York, New York; ⁴ Departments of Biostatistics and Research Epidemiology, ⁵ Surgical Pathology, and ⁶ Medical Genetics, Henry Ford Health System and ⁷ Population Studies and Prevention Program, Karmanos Cancer Institute, Wayne State University, School of Medicine, Detroit, Michigan

Requests for reprints: Benjamin A. Rybicki, Department of Biostatistics and Research Epidemiology, Henry Ford Health System, 1 Ford Place, 3E, Detroit, MI 48202. Phone: 313-874-6399; Fax: 313-874-6730. E-mail: brybick1{at}hfhs.org

Polycyclic aromatic hydrocarbon (PAH)-DNA adducts may induce mutations that contribute to carcinogenesis. We evaluated potential associations between smoking and polymorphisms in PAH metabolism [CYP1A1 Ile⁴⁶²Val, CYP1B1 Ala¹¹⁹Ser and Leu⁴³²Val, microsomal epoxide hydrolase (mEH) Tyr¹¹³His and His¹³⁹Arg, CYP3A4 A(–392)G] and conjugation [glutathione S-transferase (GST) M1 null deletion, GSTP1 Ile¹⁰⁵Val] genes and PAH-DNA adduct levels (measured by immunohistochemistry) in tumor and nontumor prostate cells in 400 prostate cancer cases. Although no statistically significant associations were observed in the total sample, stratification by ethnicity revealed that Caucasian ever smokers compared with nonsmokers had higher adduct levels in tumor cells (mean staining intensity in absorbance units ± SE, 0.1748 ± 0.0052 versus 0.1507 ± 0.0070; P = 0.006), and Caucasians carrying two mEH ¹³⁹Arg compared with two ¹³⁹His alleles had lower adducts in tumor (0.1320 ± 0.0129 versus 0.1714 ± 0.0059; P = 0.006) and nontumor (0.1856 ± 0.0184 versus 0.2291 ± 0.0085; P = 0.03) cells. African Americans with two CYP1B1 ⁴³²Val compared with two ⁴³²Ile alleles had lower adducts in tumor cells (0.1600 ± 0.0060 versus 0.1970 ± 0.0153; P = 0.03). After adjusting for smoking status, carrying the putative "high-risk" genotype combination, the faster metabolism of PAH-epoxides to PAH-diol-epoxides (CYP1B1 ⁴³²Val/Val and mEH ¹³⁹Arg/Arg) with lower PAH-diol-epoxide conjugation (GSTP1 ¹⁰⁵Ile/Ile), was associated with increased adducts only in Caucasian nontumor cells (0.2363 ± 0.0132 versus 0.1920 ± 0.0157; P= 0.05). We present evidence, for the first time in human prostate that the association between smoking and PAH-DNA adducts differs by race and is modified by common genetic variants. (Cancer Epidemiol Biomarkers Prev 2007;16(6):1236–45)

This article has been cited by other articles:

				B. A. Rybicki, C. Neslund-Dudas, C. H. Bock, A. Rundle, A. T. Savera, J. J. Yang, N. L. Nock, and D. Tang Polycyclic Aromatic Hydrocarbon-DNA Adducts in Prostate and Biochemical Recurrence after Prostatectomy Clin. Cancer Res., February 1, 2008; 14(3): 750 - 757. [Abstract] [Full Text] [PDF]

				S. Koutros, A. J. Cross, D. P. Sandler, J. A. Hoppin, X. Ma, T. Zheng, M. C.R. Alavanja, and R. Sinha Meat and Meat Mutagens and Risk of Prostate Cancer in the Agricultural Health Study Cancer Epidemiol. Biomarkers Prev., January 1, 2008; 17(1): 80 - 87. [Abstract] [Full Text] [PDF]