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[Cancer Research 61, 1354-1357, February 15, 2001]
© 2001 American Association for Cancer Research

Advances in Brief

Modulation of Nucleotide Excision Repair Capacity by XPD Polymorphisms in Lung Cancer Patients1

Margaret R. Spitz2, Xifeng Wu, Yunfei Wang, Li-E Wang, Sanjay Shete, Christopher I. Amos, Zhaozheng Guo, Lei Lei, Harvey Mohrenweiser and Qingyi Wei

Department of Epidemiology, The University of Texas M. D. Anderson Cancer Center, Houston, Texas 77030 [M. R. S., X. W., Y. W., L-E. W., S. S., C. I. A., Z. G., L. L., Q. W.], and Lawrence Livermore Laboratory, Livermore, California 94550 [H. M.]

Sequence variations have been identified in a number of DNA repair genes, including XPD, but the effect of these polymorphisms on DNA repair capacity (DRC) is uncertain. We therefore examined XPD polymorphisms at Lys751Gln and Asp312Asn in 341 white lung cancer cases and 360 age-, sex-, ethnicity-, and smoking-matched controls accrued in a hospital-based molecular epidemiological study of susceptibility markers for lung cancer. As previously reported, DRC was statistically significantly lower in the cases than in the controls (7.8% versus 9.5%; P < 0.001), which represents an average 18% reduction among the cases. The variant Lys751Gln and Asp312Asn allele frequencies were 0.36 and 0.29, respectively, for the cases and 0.33 and 0.27, respectively, for the controls. For subjects homozygous for the variant genotype at either locus, the adjusted odds ratio [95% confidence interval (CI)] was 1.84 (1.11–3.04; P = 0.018, for trend). Both cases and controls with the wild-type genotypes exhibited the most proficient DRC. The risk (95% CI) for suboptimal DRC (defined as less than the median DRC value among the controls) was 1.57 (0.74–3.35) for those with the Gln/Gln751 genotype. For cases with the Asn/Asn312 genotype, the risk (95% CI) was 3.50 (1.06–11.59). For cases who were homozygous at either locus, the risk was 2.29 (1.03–5.12; P = 0.048, for trend). The pattern was less evident among the controls, although there was a nonsignificant 41% increase in the risk of suboptimal DRC for controls who were homozygous at either locus. These results suggest that the two XPD polymorphisms have a modulating effect on DRC, especially in the cases.




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 CarcinogenesisHome page
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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 Cancer Epidemiol. Biomarkers Prev.Home page
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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 Cancer Epidemiol. Biomarkers Prev.Home page
G. Matullo, M. Peluso, S. Polidoro, S. Guarrera, A. Munnia, V. Krogh, G. Masala, F. Berrino, S. Panico, R. Tumino, et al.
Combination of DNA Repair Gene Single Nucleotide Polymorphisms and Increased Levels of DNA Adducts in a Population-based Study
Cancer Epidemiol. Biomarkers Prev., July 1, 2003; 12(7): 674 - 677.
[Abstract] [Full Text] [PDF]

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 JNCI J Natl Cancer InstHome page
M. B. Schabath, M. R. Spitz, H. B. Grossman, K. Zhang, C. P. Dinney, P.-J. Zheng, and X. Wu
Genetic Instability in Bladder Cancer Assessed by the Comet Assay
J Natl Cancer Inst, April 2, 2003; 95(7): 540 - 547.
[Abstract] [Full Text] [PDF]

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 Cancer Epidemiol. Biomarkers Prev.Home page
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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 CarcinogenesisHome page
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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 MutagenesisHome page
R. Kumar, S. Angelini, and K. Hemminki
Simultaneous detection of the exon 10 polymorphism and a novel intronic single base insertion polymorphism in the XPD gene using single strand conformation polymorphism
Mutagenesis, March 1, 2003; 18(2): 207 - 209.
[Abstract] [Full Text] [PDF]

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 MutagenesisHome page
S. Benhamou and A. Sarasin
ERCC2/XPD gene polymorphisms and cancer risk
Mutagenesis, November 1, 2002; 17(6): 463 - 469.
[Abstract] [Full Text] [PDF]

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 JNCI J Natl Cancer InstHome page
P. G. Shields
Tobacco Smoking, Harm Reduction, and Biomarkers
J Natl Cancer Inst, October 2, 2002; 94(19): 1435 - 1444.
[Abstract] [Full Text] [PDF]

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 Cancer Epidemiol. Biomarkers Prev.Home page
M. C. Stern, L. R. Johnson, D. A. Bell, and J. A. Taylor
XPD Codon 751 Polymorphism, Metabolism Genes, Smoking, and Bladder Cancer Risk
Cancer Epidemiol. Biomarkers Prev., October 1, 2002; 11(10): 1004 - 1011.
[Abstract] [Full Text] [PDF]

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 Cancer Epidemiol. Biomarkers Prev.Home page
H. W. Mohrenweiser, T. Xi, J. Vazquez-Matias, and I. M. Jones
Identification of 127Amino Acid Substitution Variants in Screening 37 DNA Repair Genes in Humans
Cancer Epidemiol. Biomarkers Prev., October 1, 2002; 11(10): 1054 - 1064.
[Abstract] [Full Text] [PDF]

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 Cancer Res.Home page
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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 Arch Otolaryngol Head Neck SurgHome page
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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 CarcinogenesisHome page
S. Chen, D. Tang, K. Xue, L. Xu, G. Ma, Y. Hsu, and S. S. Cho
DNA repair gene XRCC1 and XPD polymorphisms and risk of lung cancer in a Chinese population
Carcinogenesis, August 1, 2002; 23(8): 1321 - 1325.
[Abstract] [Full Text] [PDF]

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 JNCI J Natl Cancer InstHome page
C. H. Bosken, Q. Wei, C. I. Amos, and M. R. Spitz
An Analysis of DNA Repair as a Determinant of Survival in Patients With Non-Small-Cell Lung Cancer
J Natl Cancer Inst, July 17, 2002; 94(14): 1091 - 1099.
[Abstract] [Full Text] [PDF]

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 Cancer Epidemiol. Biomarkers Prev.Home page
Y. Zheng, H. Shen, E. M. Sturgis, L.-E Wang, S. Shete, M. R. Spitz, and Q. Wei
Haplotypes of Two Variants in p16 (CDKN2/MTS-1/INK4a) Exon 3 and Risk of Squamous Cell Carcinoma of the Head and Neck: A Case-Control Study
Cancer Epidemiol. Biomarkers Prev., July 1, 2002; 11(7): 640 - 645.
[Abstract] [Full Text] [PDF]

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 CarcinogenesisHome page
S.-M. Hou, S. Falt, S. Angelini, K. Yang, F. Nyberg, B. Lambert, and K. Hemminki
The XPD variant alleles are associated with increased aromatic DNA adduct level and lung cancer risk
Carcinogenesis, April 1, 2002; 23(4): 599 - 603.
[Abstract] [Full Text] [PDF]

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 Cancer Res.Home page
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
Gene-Environment Interaction for the ERCC2 Polymorphisms and Cumulative Cigarette Smoking Exposure in Lung Cancer
Cancer Res., March 1, 2002; 62(5): 1377 - 1381.
[Abstract] [Full Text] [PDF]

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 CarcinogenesisHome page
Y. Qiao, M. R. Spitz, H. Shen, Z. Guo, S. Shete, M. Hedayati, L. Grossman, H. Mohrenweiser, and Q. Wei
Modulation of repair of ultraviolet damage in the host-cell reactivation assay by polymorphic XPC and XPD/ERCC2 genotypes
Carcinogenesis, February 1, 2002; 23(2): 295 - 299.
[Abstract] [Full Text] [PDF]

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 Cancer Res.Home page
D. J. Park, J. Stoehlmacher, W. Zhang, D. D. Tsao-Wei, S. Groshen, and H.-J. Lenz
A Xeroderma Pigmentosum Group D Gene Polymorphism Predicts Clinical Outcome to Platinum-based Chemotherapy in Patients with Advanced Colorectal Cancer
Cancer Res., December 1, 2001; 61(24): 8654 - 8658.
[Abstract] [Full Text] [PDF]

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 Cancer Res.Home page
H. Seker, D. Butkiewicz, E. D. Bowman, M. Rusin, M. Hedayati, L. Grossman, and C. C. Harris
Functional Significance of XPD Polymorphic Variants: Attenuated Apoptosis in Human Lymphoblastoid Cells with the XPD 312 Asp/Asp Genotype
Cancer Res., October 1, 2001; 61(20): 7430 - 7434.
[Abstract] [Full Text] [PDF]

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 JCOHome page
S. M. Lippman and M. R. Spitz
Lung Cancer Chemoprevention: An Integrated Approach
J. Clin. Oncol., September 15, 2001; 19(90001): 74s - 82.
[Abstract] [Full Text] [PDF]

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 Cancer Epidemiol. Biomarkers Prev.Home page
G. L. David-Beabes, R. M. Lunn, and S. J. London
No Association between the XPD (Lys751G1n) Polymorphism or the XRCC3 (Thr241Met) Polymorphism and Lung Cancer Risk
Cancer Epidemiol. Biomarkers Prev., August 1, 2001; 10(8): 911 - 912.
[Full Text] [PDF]


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