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 Gu, J. Articles by Wu, X. Search for Related Content PubMed PubMed Citation Articles by Gu, J. Articles by Wu, X.

Nucleotide Excision Repair Gene Polymorphisms and Recurrence after Treatment for Superficial Bladder Cancer

Departments of ¹ Epidemiology and ² Urology, The University of Texas M.D. Anderson Cancer Center, Houston, Texas, and ³ Department of Epidemiology and Public Health, Yale University, New Haven, Connecticut

Requests for reprints: Xifeng Wu, Department of Epidemiology, Unit 1340, The University of Texas MD Anderson Cancer Center, 1155 Pressler Boulevard, Houston, TX 77030. Phone: 713-745-2485; Fax: 713-792-4657; E-mail: xwu{at}mdanderson.org.

Purpose: Interindividual differences in DNA repair capacity not only modify individual susceptibility to carcinogenesis, but also affect individual response to cancer treatment. Nucleotide excision repair (NER) is one of the major DNA repair pathways in mammalian cells involved in the removal of a wide variety of DNA lesions. Polymorphisms in NER genes may influence DNA repair capacity and affect clinical outcome of bladder cancer treatment.

Experimental Design: To test the influence of NER gene polymorphisms on superficial bladder cancer outcome (recurrence and progression), we conducted a follow-up study of 288 patients with superficial bladder cancer. Median follow-up among patients who were recurrence-free at the end of observation was 21.7 months from diagnosis. The specific polymorphic loci examined include XPA [A/G at 5' untranslated region (UTR)], XPC (poly AT, Ala⁴⁹⁹Val, Lys⁹³⁹Gln), XPD (Asp³¹²Asn, Lys⁷⁵¹Gln), XPG (His¹¹⁰⁴Asp), ERCC 1 (G/T at 3' UTR), and ERCC6 (Met¹⁰⁹⁷Val, Arg¹²³⁰Pro).

Results: The ERCC6 (Met¹⁰⁹⁷Val) polymorphism had a significant impact on recurrence: carriers of at least one variant allele (Val) had a significantly higher recurrence risk than carriers of the wild-type allele (Met/Met; hazard ratio, 1.54; 95% confidence interval, 1.02-2.33). There were no overall statistically significant differences in the distributions of the other polymorphisms between patients with and without recurrence. However, when we combined these variant genotypes, there was a significant trend for an increased recurrence risk with an increasing number of putative high-risk alleles. Using individuals with five or fewer putative high-risk alleles as the reference group, individuals with six to seven risk alleles and individuals with eight or more risk alleles had higher recurrence risks, with hazard ratios of 0.92 (0.54-1.57) and 2.53 (1.48-4.30), respectively (P for trend < 0.001). There was also a significant trend for shorter recurrence-free survival time with increasing number of variant alleles (log rank test, P = 0.0007). When we stratified the patients according to intravesical Bacillus Calmette-Guerin treatment, we found a significant trend for shorter recurrence-free survival time in patients with variant alleles of XPA or ERCC6 polymorphisms who received Bacillus Calmette-Guerin treatment (log rank test, P = 0.078 and 0.022, respectively). There were no significant individual or joint associations between these polymorphisms and progression.

Conclusions: These data suggest that interindividual differences in DNA repair capacity may have an important impact on superficial bladder cancer recurrence. A pathway-based approach is preferred to study the effects of individual polymorphism on clinical outcomes.

Key Words: bladder cancer • polymorphism • nucleotide excision repair • XPA • ERCC6 • Genotourinary cancers: bladder

This article has been cited by other articles:

				S. Sakano, Y. Hinoda, N. Okayama, Y. Kawai, Y. Korenaga, S. Eguchi, K. Nagao, C. Ohmi, and K. Naito The association of DNA repair gene polymorphisms with the development and progression of renal cell carcinoma Ann. Onc., November 1, 2007; 18(11): 1817 - 1827. [Abstract] [Full Text] [PDF]

				K. D. Crew, M. D. Gammon, M. B. Terry, F. F. Zhang, L. B. Zablotska, M. Agrawal, J. Shen, C.-M. Long, S. M. Eng, S. K. Sagiv, et al. Polymorphisms in Nucleotide Excision Repair Genes, Polycyclic Aromatic Hydrocarbon-DNA Adducts, and Breast Cancer Risk Cancer Epidemiol. Biomarkers Prev., October 1, 2007; 16(10): 2033 - 2041. [Abstract] [Full Text] [PDF]

				W. Wang, M. R. Spitz, H. Yang, C. Lu, D. J. Stewart, and X. Wu Genetic Variants in Cell Cycle Control Pathway Confer Susceptibility to Lung Cancer Clin. Cancer Res., October 1, 2007; 13(19): 5974 - 5981. [Abstract] [Full Text] [PDF]

				S. C. Sak, J. H. Barrett, A. B. Paul, D. T. Bishop, and A. E. Kiltie Comprehensive Analysis of 22 XPC Polymorphisms and Bladder Cancer Risk Cancer Epidemiol. Biomarkers Prev., December 1, 2006; 15(12): 2537 - 2541. [Abstract] [Full Text] [PDF]

				M. Monzo, S. Brunet, A. Urbano-Ispizua, A. Navarro, G. Perea, J. Esteve, R. Artells, M. Granell, J. Berlanga, J. M. Ribera, et al. Genomic polymorphisms provide prognostic information in intermediate-risk acute myeloblastic leukemia Blood, June 15, 2006; 107(12): 4871 - 4879. [Abstract] [Full Text] [PDF]