© 2000 by Oxford University Press
Journal of the National Cancer Institute, Vol. 92, No. 21, 1764-1772,
November 1, 2000
© 2000 Oxford University Press
Repair of Tobacco Carcinogen-Induced DNA Adducts and Lung Cancer Risk: a Molecular Epidemiologic Study
Affiliations of authors: Q. Wei, L. Cheng, C. I. Amos, L.-E. Wang, Z. Guo, M. R. Spitz (Department of Epidemiology, Division of Cancer Prevention), W. K. Hong (Department of Thoracic and Head and Neck Medical Oncology), The University of Texas M. D. Anderson Cancer Center, Houston.
Correspondence to: Qingyi Wei, M.D., Ph.D., Department of Epidemiology, The University of Texas M. D. Anderson Cancer Center, Box 189, 1515 Holcombe Blvd., Houston, TX 77030 (e-mail: qwei{at}mdanderson.org).
Background: Only a fraction of cigarette smokers develop lung cancer, suggesting that people differ in their susceptibility to this disease. We investigated whether differences in DNA repair capacity (DRC) for repairing tobacco carcinogen-induced DNA damage are associated with differential susceptibility to lung cancer. Methods: From August 1, 1995, through April 30, 1999, we conducted a hospital-based, case–control study of 316 newly diagnosed lung cancer patients and 316 cancer-free control subjects matched on age, sex, and smoking status. DRC was measured in cultured lymphocytes with the use of the host-cell reactivation assay with a reporter gene damaged by a known activated tobacco carcinogen, benzo[a]pyrene diol epoxide. Statistical tests were two-sided. Results: Overall, lower DRC was observed in case patients than in control subjects (P<.001) and was associated with a greater than twofold increased risk of lung cancer. Compared with the highest DRC quartile in the control subjects and after adjustment for age, sex, pack-years of smoking, family history of cancer, and other covariates, reduced DRC was associated with increased risk of lung cancer in a dose-dependent fashion (odds ratio [OR] = 1.8 with 95% confidence interval [CI] = 1.1–3.1, OR = 2.0 with 95% CI = 1.2–3.4, and OR = 4.3 with 95% CI = 2.6–7.2 for the second, third, and fourth quartiles, respectively; Ptrend<.001). Case patients who were younger at diagnosis (<60 years old), female, or lighter smokers or who reported a family history of cancer exhibited the lowest DRC and the highest lung cancer risk among their subgroups, suggesting that these subgroups may be especially susceptible to lung cancer. Conclusion: The results provide evidence that low DRC is associated with increased risk of lung cancer. The findings from this hospital-based, case–control study should be validated in prospective studies.
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W. Zhou, G. Liu, S. Park, Z. Wang, J. C. Wain, T. J. Lynch, L. Su, and D. C. Christiani Gene-Smoking Interaction Associations for the ERCC1 Polymorphisms in the Risk of Lung Cancer Cancer Epidemiol. Biomarkers Prev., February 1, 2005; 14(2): 491 - 496. [Abstract] [Full Text] [PDF]
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L. A. Mooney, A. M. Madsen, D. Tang, M. A. Orjuela, W.-Y. Tsai, E. R. Garduno, and F. P. Perera Antioxidant Vitamin Supplementation Reduces Benzo(a)pyrene-DNA Adducts and Potential Cancer Risk in Female Smokers Cancer Epidemiol. Biomarkers Prev., January 1, 2005; 14(1): 237 - 242. [Abstract] [Full Text] [PDF]
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X. Wu, J. A. Roth, H. Zhao, S. Luo, Y.-L. Zheng, S. Chiang, and M. R. Spitz Cell Cycle Checkpoints, DNA Damage/Repair, and Lung Cancer Risk Cancer Res., January 1, 2005; 65(1): 349 - 357. [Abstract] [Full Text] [PDF]
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S. Jonsson, U. Thorsteinsdottir, D. F. Gudbjartsson, H. H. Jonsson, K. Kristjansson, S. Arnason, V. Gudnason, H. J. Isaksson, J. Hallgrimsson, J. R. Gulcher, et al. Familial Risk of Lung Carcinoma in the Icelandic Population JAMA, December 22, 2004; 292(24): 2977 - 2983. [Abstract] [Full Text] [PDF]
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M. Peluso, M. Neri, G. Margarino, C. Mereu, A. Munnia, M. Ceppi, M. Buratti, R. Felletti, F. Stea, R. Quaglia, et al. Comparison of DNA adduct levels in nasal mucosa, lymphocytes and bronchial mucosa of cigarette smokers and interaction with metabolic gene polymorphisms Carcinogenesis, December 1, 2004; 25(12): 2459 - 2465. [Abstract] [Full Text] [PDF]
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M. S. Marin, M. F. Lopez-Cima, L. Garcia-Castro, T. Pascual, M. G. Marron, and A. Tardon Poly (AT) Polymorphism in Intron 11 of the XPC DNA Repair Gene Enhances the Risk of Lung Cancer Cancer Epidemiol. Biomarkers Prev., November 1, 2004; 13(11): 1788 - 1793. [Abstract] [Full Text] [PDF]
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G. Li, L.-E Wang, R. M. Chamberlain, C. I. Amos, M. R. Spitz, and Q. Wei p73 G4C14-to-A4T14 Polymorphism and Risk of Lung Cancer Cancer Res., October 1, 2004; 64(19): 6863 - 6866. [Abstract] [Full Text] [PDF]
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 M. Taron, R. Rosell, E. Felip, P. Mendez, J. Souglakos, M. S. Ronco, C. Queralt, J. Majo, J. M. Sanchez, J. J. Sanchez, et al. BRCA1 mRNA expression levels as an indicator of chemoresistance in lung cancer Hum. Mol. Genet., October 1, 2004; 13(20): 2443 - 2449. [Abstract] [Full Text] [PDF]
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G. Li, E. M. Sturgis, L.-E. Wang, R. M. Chamberlain, C. I. Amos, M. R. Spitz, A. K. El-Naggar, W. K. Hong, and Q. Wei Association of a p73 exon 2 G4C14-to-A4T14 polymorphism with risk of squamous cell carcinoma of the head and neck Carcinogenesis, October 1, 2004; 25(10): 1911 - 1916. [Abstract] [Full Text] [PDF]
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 J. Olak and Y. Colson Gender differences in lung cancer: Have we really come a long way, baby? J. Thorac. Cardiovasc. Surg., September 1, 2004; 128(3): 346 - 351. [Full Text] [PDF]
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Q. Shi, L.-E. Wang, M. L. Bondy, A. Brewster, S. E. Singletary, and Q. Wei Reduced DNA repair of benzo[a]pyrene diol epoxide-induced adducts and common XPD polymorphisms in breast cancer patients Carcinogenesis, September 1, 2004; 25(9): 1695 - 1700. [Abstract] [Full Text] [PDF]
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S. Gurubhagavatula, G. Liu, S. Park, W. Zhou, L. Su, J. C. Wain, T. J. Lynch, D. S. Neuberg, and D. C. Christiani XPD and XRCC1 Genetic Polymorphisms Are Prognostic Factors in Advanced Non--Small-Cell Lung Cancer Patients Treated With Platinum Chemotherapy J. Clin. Oncol., July 1, 2004; 22(13): 2594 - 2601. [Abstract] [Full Text] [PDF]
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B. Hao, H. Wang, K. Zhou, Y. Li, X. Chen, G. Zhou, Y. Zhu, X. Miao, W. Tan, Q. Wei, et al. Identification of Genetic Variants in Base Excision Repair Pathway and Their Associations with Risk of Esophageal Squamous Cell Carcinoma Cancer Res., June 15, 2004; 64(12): 4378 - 4384. [Abstract] [Full Text] [PDF]
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Z. Zhang, Q. Shi, L.-E Wang, E. M. Sturgis, M. R. Spitz, A. K. El-Naggar, W. K. Hong, and Q. Wei No Association between hOGG1 Ser326Cys Polymorphism and Risk of Squamous Cell Carcinoma of the Head and Neck Cancer Epidemiol. Biomarkers Prev., June 1, 2004; 13(6): 1081 - 1083. [Full Text] [PDF]
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 A. S. Tsao, E. S. Kim, and W. K. Hong Chemoprevention of Cancer CA Cancer J Clin, May 1, 2004; 54(3): 150 - 180. [Abstract] [Full Text] [PDF]
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J. D. Patel, P. B. Bach, and M. G. Kris Lung Cancer in US Women: A Contemporary Epidemic JAMA, April 14, 2004; 291(14): 1763 - 1768. [Abstract] [Full Text] [PDF]
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W.-M. Gao, M. Romkes, J. M. Siegfried, J. D. Luketich, and P. Keohavong No Association between the XPD 312, 751, or XRCC1 399 Polymorphisms and K-ras Gene Mutation in Smoking Non-Small-Cell Lung Cancer Cancer Epidemiol. Biomarkers Prev., April 1, 2004; 13(4): 673 - 675. [Full Text] [PDF]
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C. J. Etzel, C. I. Amos, and M. R. Spitz Risk for Smoking-Related Cancer among Relatives of Lung Cancer Patients Cancer Res., December 1, 2003; 63(23): 8531 - 8535. [Abstract] [Full Text] [PDF]
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Q. Wei, H. Shen, L.-E Wang, C. M. Duphorne, P. C. Pillow, Z. Guo, Y. Qiao, and M. R. Spitz Association between Low Dietary Folate Intake and Suboptimal Cellular DNA Repair Capacity Cancer Epidemiol. Biomarkers Prev., October 1, 2003; 12(10): 963 - 969. [Abstract] [Full Text] [PDF]
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W.-M. Gao, M. Romkes, R. D. Day, J. M. Siegfried, J. D. Luketich, H. H. Mady, M. F. Melhem, and P. Keohavong Association of the DNA repair gene XPD Asp312Asn polymorphism with p53 gene mutations in tobacco-related non-small cell lung cancer Carcinogenesis, October 1, 2003; 24(10): 1671 - 1676. [Abstract] [Full Text] [PDF]
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A. L. Sabichi, M.-F. Demierre, E. T. Hawk, C. E. Lerman, and S. M. Lippman Frontiers in Cancer Prevention Research Cancer Res., September 15, 2003; 63(18): 5649 - 5655. [Full Text] [PDF]
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 T. Paz-Elizur, M. Krupsky, S. Blumenstein, D. Elinger, E. Schechtman, and Z. Livneh DNA Repair Activity for Oxidative Damage and Risk of Lung Cancer J Natl Cancer Inst, September 3, 2003; 95(17): 1312 - 1319. [Abstract] [Full Text] [PDF]
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M. R. Spitz, Q. Wei, Q. Dong, C. I. Amos, and X. Wu Genetic Susceptibility to Lung Cancer: The Role of DNA Damage and Repair Cancer Epidemiol. Biomarkers Prev., August 1, 2003; 12(8): 689 - 698. [Full Text] [PDF]
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E. Speina, M. Zielinska, A. Barbin, D. Gackowski, J. Kowalewski, M. A. Graziewicz, J. A. Siedlecki, R. Olinski, and B. Tudek Decreased Repair Activities of 1,N6-Ethenoadenine and 3,N4-Ethenocytosine in Lung Adenocarcinoma Patients Cancer Res., August 1, 2003; 63(15): 4351 - 4357. [Abstract] [Full Text] [PDF]
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W. Zhou, G. Liu, D. P. Miller, S. W. Thurston, L. L. Xu, J. C. Wain, T. J. Lynch, L. Su, and D. C. Christiani Polymorphisms in the DNA Repair Genes XRCC1 and ERCC2, Smoking, and Lung Cancer Risk Cancer Epidemiol. Biomarkers Prev., April 1, 2003; 12(4): 359 - 365. [Abstract] [Full Text] [PDF]
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X. Wu, H. Zhao, Q. Wei, C. I. Amos, K. Zhang, Z. Guo, Y. Qiao, W. K. Hong, and M. R. Spitz XPA polymorphism associated with reduced lung cancer risk and a modulating effect on nucleotide excision repair capacity Carcinogenesis, March 1, 2003; 24(3): 505 - 509. [Abstract] [Full Text] [PDF]
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Q. Wei, J. E. Lee, J. E. Gershenwald, M. I. Ross, P. F. Mansfield, S. S. Strom, L.-E Wang, Z. Guo, Y. Qiao, C. I. Amos, et al. Repair of UV Light-Induced DNA Damage and Risk of Cutaneous Malignant Melanoma J Natl Cancer Inst, February 19, 2003; 95(4): 308 - 315. [Abstract] [Full Text] [PDF]
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H. Shen, L. Wang, M. R. Spitz, W. K. Hong, L. Mao, and Q. Wei A Novel Polymorphism in Human Cytosine DNA-Methyltransferase-3B Promoter Is Associated with an Increased Risk of Lung Cancer Cancer Res., September 1, 2002; 62(17): 4992 - 4995. [Abstract] [Full Text] [PDF]
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 E. M. Sturgis, K. R. Dahlstrom, M. R. Spitz, and Q. Wei DNA Repair Gene ERCC1 and ERCC2/XPD Polymorphisms and Risk of Squamous Cell Carcinoma of the Head and Neck Arch Otolaryngol Head Neck Surg, September 1, 2002; 128(9): 1084 - 1088. [Abstract] [Full Text] [PDF]
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E. J. Duell, E. A. Holly, P. M. Bracci, J. K. Wiencke, and K. T. Kelsey A Population-based Study of the Arg399Gln Polymorphism in X-Ray Repair Cross- Complementing Group 1 (XRCC1) and Risk of Pancreatic Adenocarcinoma Cancer Res., August 15, 2002; 62(16): 4630 - 4636. [Abstract] [Full Text] [PDF]
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