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Chapter 30 : DNA Polymorphisms in Gatekeeper and Guardian Genes

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Abstract:

This chapter focuses solely on the human as an experimental organism. The data discussed are derived from unique experimental approaches. There is substantial evidence that cancer segregates in many additional families, albeit at a reduced frequency compared with that for the more severe syndromes. There is also epidemiological evidence for significant variation in DNA repair capacity among individuals in the population and evidence that those with mildly reduced capacity may be more likely to exhibit a cancer predisposition. A great many publications have proposed associations between specific genetic variants (polymorphisms) in DNA repair and/or damage response genes and a cancer predisposition. Evidence documenting the impact of a polymorphism on protein function is generally lacking. Thus, the appreciation of a specific role for the variant proteins in disease, while logical in theory, remains an important aspect of DNA repair and mutagenesis that is still under development.

Citation: Errol C, Graham C, Wolfram S, Richard D, Roger A, Tom E. 2006. DNA Polymorphisms in Gatekeeper and Guardian Genes, p 1049-1080. In DNA Repair and Mutagenesis, Second Edition. ASM Press, Washington, DC. doi: 10.1128/9781555816704.ch30

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Restriction Fragment Length Polymorphism
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Base Excision Repair
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Nucleotide Excision Repair
0.41278192
0.421633
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Figures

Image of Figure 30–1
Figure 30–1

The NCBI discovery space. The figure illustrates how records in the dbSNP database are cross-annotated within other internal information resources. More information is available at http://www.ncbi.nlm.nih.gov/About/primer/snps.html (Adapted from NCBI and from reference .)

Citation: Errol C, Graham C, Wolfram S, Richard D, Roger A, Tom E. 2006. DNA Polymorphisms in Gatekeeper and Guardian Genes, p 1049-1080. In DNA Repair and Mutagenesis, Second Edition. ASM Press, Washington, DC. doi: 10.1128/9781555816704.ch30
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Image of Figure 30–2
Figure 30–2

Relationship between SNPs and the HapMap. (A) SNPs are identified in DNA samples from various populations. (B) Adjacent SNPs that are inherited as blocks called haplotypes. (C) Tag SNPs within haplotypes are those markers that uniquely distinguish the different haplotypes for a larger set of markers. For example, by genotyping the three tag SNPs shown in the figure, each of the four haplotypes shown can be identified. (Adapted from NCBI at http://www.hapmap.org/whatishapmap.html.en.)

Citation: Errol C, Graham C, Wolfram S, Richard D, Roger A, Tom E. 2006. DNA Polymorphisms in Gatekeeper and Guardian Genes, p 1049-1080. In DNA Repair and Mutagenesis, Second Edition. ASM Press, Washington, DC. doi: 10.1128/9781555816704.ch30
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Image of Figure 30–3
Figure 30–3

Repair-related genes mapping in close proximity to the XPC gene on human chromosome 3p25.1-25.3.

Citation: Errol C, Graham C, Wolfram S, Richard D, Roger A, Tom E. 2006. DNA Polymorphisms in Gatekeeper and Guardian Genes, p 1049-1080. In DNA Repair and Mutagenesis, Second Edition. ASM Press, Washington, DC. doi: 10.1128/9781555816704.ch30
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Image of Figure 30–4
Figure 30–4

Genotyping by differential array hybridization. (A) A representative fluorescence image of an entire oligonucleotide probe array following hybridization is shown. (B) Scheme for genotyping of an polymorphism in the Columbia and Landsberg ecotypes on a variant-detector high-density oligonucleotide probe array. The array is designed to interrogate not only the polymorphic site (marked with an asterisk) by using four 25-mer probes that have an A, C, G, or T at the center position (N) but also five flanking bases on either side, adding to the specificity of the assay. The target DNA hybridizes most strongly to a sequence representing a perfect match. Therefore, the probe with the correct base at each center position will produce the strongest hybridization signal. (C) Actual and schematic hybridization patterns are shown for homozygous Columbia (T/T genotype) (top), homozygous Landsberg (C/C genotype) (bottom), and a heterozygous recombinant (T/C genotype) (center). Hybridization of the T allele to the C allele variant-detector array (or the C allele on the T variant-detector array) yields a strong hybridization signal only when the base is varied at the polymorphic site, restoring the correct sequence match. Variation at a second site left or right of the polymorphic site completely disrupts hybridization of an allele on the opposite variant-detector array, since the allele now has a twobase mismatch, but only partially affects hybridization on the correct variant-detector array for some sites, since these are the only mismatches. (Adapted from reference .)

Citation: Errol C, Graham C, Wolfram S, Richard D, Roger A, Tom E. 2006. DNA Polymorphisms in Gatekeeper and Guardian Genes, p 1049-1080. In DNA Repair and Mutagenesis, Second Edition. ASM Press, Washington, DC. doi: 10.1128/9781555816704.ch30
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Figure 30-5

Schematic of the mismatch repair detection (MRD) procedure. MRD utilizes two vectors that are identical except for a 5-bp deletion in the gene coding for Cre recombinase on one of the two vectors. DNA fragments, such as exons, are cloned in the vector containing the active and grown in a bacterial strain that lacks the Dam methylase. These clones, referred to as the standard panel, are made only once and serve as sequence comparison templates for exons from each person to be tested. (A) Heteroduplex formation. DNA fragments being tested are PCR amplified from each individual and pooled. In the example presented, samples are tested for a total of 35 different sequences (illustrated by shades of gold). Linearized methylated vector DNA with a 5-bp deletion within the gene is shown as a grey line, and the 5-bp deletion is shown as a black square. Unmethylated standards are shown in black circles and inserts, with colors and numbers corresponding to the 35 different fragments amplified from the test sample. The components are placed in a single tube, denatured, and reannealed to form heteroduplexes between the unmethylated single-stranded standard, complementary PCR product, and vector with the deleted gene. Hemimethylated heteroduplex circles are ligated with ligase, unligated molecules are removed after treatment with exonuclease III, and the circles are transformed into an strain (MS) carrying an F’ factor with Tet and Str genes flanked by two sites. This strain carries a streptomycin resistance gene on its chromosome. (B) Identification of mismatches. Heteroduplex molecules without mismatch (i.e., no variation between the standard and the DNA fragment that is being tested) will replicate normally, and both plasmids carrying the active and inactive Cre will be present. The active Cre protein (grey circles) recombines the two sites, leading to the loss of the Tet and Str genes and leaving the cells tetracycline sensitive and streptomycin resistant. In the presence of a mismatch in the heteroduplex, MMR occurs and the unmethylated strand carrying the deleted gene is degraded. These cells cannot recombine the two sites, retain the Tet and Str genes on the F’ factor, and survive in the presence of tetracycline but not streptomycin (the streptomycin-sensitive allele is dominant over the resistant allele). (C) Identification of the fragment content of variant and nonvariant pools. Growing the same transformation mixture on two plates containing either tetracycline or streptomycin facilitates the production of pools representing clones that contain variation and those that do not. If the assorted inserts designated 1 to 35 vary in size, then analysis and comparison of the pools by restriction digestion and/or gel electrophoresis provide a means to identify those inserts that are represented by variation. (Adapted from reference .)

Citation: Errol C, Graham C, Wolfram S, Richard D, Roger A, Tom E. 2006. DNA Polymorphisms in Gatekeeper and Guardian Genes, p 1049-1080. In DNA Repair and Mutagenesis, Second Edition. ASM Press, Washington, DC. doi: 10.1128/9781555816704.ch30
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Image of Figure 30.6
Figure 30.6

Double D-loop formation assay. (A) A DNA “incoming” oligonucleotide (oligo) is converted to a recombinant filament with RecA in the presence of ATPγ-S. (B) RecA catalyzes the pairing and strand invasion of a duplex, creating a D-loop intermediate. (C) The D-loop intermediate is stabilized, and a double D-loop is produced by an “annealing” oligonucleotide complementary to the displaced strand. (D) The resulting double D-loop is sufficiently stable to remain intact following removal of all RecA protein. (Adapted from reference .)

Citation: Errol C, Graham C, Wolfram S, Richard D, Roger A, Tom E. 2006. DNA Polymorphisms in Gatekeeper and Guardian Genes, p 1049-1080. In DNA Repair and Mutagenesis, Second Edition. ASM Press, Washington, DC. doi: 10.1128/9781555816704.ch30
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Image of Figure 30–7
Figure 30–7

Comparisons of the DNA repair capacity measured for women with (Breast) and without (Controls) breast carcinoma. The capacity was measured in lymphocytes, using the host cell reactivation assay. Values are expressed as the mean, and 1 standard error of the mean is shown by the error bars. (Adapted from reference .)

Citation: Errol C, Graham C, Wolfram S, Richard D, Roger A, Tom E. 2006. DNA Polymorphisms in Gatekeeper and Guardian Genes, p 1049-1080. In DNA Repair and Mutagenesis, Second Edition. ASM Press, Washington, DC. doi: 10.1128/9781555816704.ch30
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Image of Figure 30–8
Figure 30–8

Relationship between donor age and DNA repair capacity, using a UV-irradiated pCMVcat plasmid reactivation assay. Activity was determined using fibroblast cell lines from 20 normal donors. The mean standard error of the mean of triplicate determinations is shown for each donor. The dashed line is the least-squares linear-regression line, and the colored zone illustrates the 95% confidence interval. CAT, chloramphenicol acetyltransferase. (Adapted from reference .)

Citation: Errol C, Graham C, Wolfram S, Richard D, Roger A, Tom E. 2006. DNA Polymorphisms in Gatekeeper and Guardian Genes, p 1049-1080. In DNA Repair and Mutagenesis, Second Edition. ASM Press, Washington, DC. doi: 10.1128/9781555816704.ch30
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Figure 30–9

Comparing the two-hit and the haploinsufficiency models of tumorigenesis. (Top) In the two-hit model, tumors result when both alleles of a tumor suppressor gene (TSG) are consecutively inactivated. (Bottom) In the haploinsufficiency model, reduced expression from only one functional allele leads to an altered cellular environment that might confer a selective growth advantage, increased genetic instability, or a new specific cellular phenotype. Such phenotypes might be realized following additional tumor-promoting events such as the acquisition of mutations in different tumor suppressor genes or oncogenes. (Adapted from reference .)

Citation: Errol C, Graham C, Wolfram S, Richard D, Roger A, Tom E. 2006. DNA Polymorphisms in Gatekeeper and Guardian Genes, p 1049-1080. In DNA Repair and Mutagenesis, Second Edition. ASM Press, Washington, DC. doi: 10.1128/9781555816704.ch30
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Image of Figure 30–10
Figure 30–10

Model for the dependence of biological functions on protein concentration. Roles in embryonic development (dashed line) and tumor suppression (solid line) are illustrated for several tumor suppressor genes. Arrows depict theoretical protein concentrations for haploid and diploid gene copy numbers. (A) p53 and p27 are examples of genes not required for development; however, haploidy lends to tumor predisposition. (B) RB1 is required for both embryonic development and tumor suppression, but haploidy accommodates the former and nearly the latter. (C) Haploinsufficiency for a gene like CBFA2/RUNX1/AML1 may hence be barely sufficient to fully support development and tumor suppression. For the last two panels, loss of the normal allele would affect development. However, for all three panels, loss of the normal allele would contribute to a tumorigenic state. (Adapted from reference .)

Citation: Errol C, Graham C, Wolfram S, Richard D, Roger A, Tom E. 2006. DNA Polymorphisms in Gatekeeper and Guardian Genes, p 1049-1080. In DNA Repair and Mutagenesis, Second Edition. ASM Press, Washington, DC. doi: 10.1128/9781555816704.ch30
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Image of Figure 30–11
Figure 30–11

The duration of smoking increases the risk of lung cancer. This effect is more dramatic in heterozygotes and homozygotes with the CYP1A1 MsPI polymorphism than for homozygote “normal” individuals. (Adapted from reference .)

Citation: Errol C, Graham C, Wolfram S, Richard D, Roger A, Tom E. 2006. DNA Polymorphisms in Gatekeeper and Guardian Genes, p 1049-1080. In DNA Repair and Mutagenesis, Second Edition. ASM Press, Washington, DC. doi: 10.1128/9781555816704.ch30
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Image of Figure 30–12
Figure 30–12

The most extensively characterized gene polymorphisms, Asp312Asn and Lys751Gln, are at sites that are not conserved. Shades of gold illustrate regions of greatest conservation, while grey identifies nonconservative changes.

Citation: Errol C, Graham C, Wolfram S, Richard D, Roger A, Tom E. 2006. DNA Polymorphisms in Gatekeeper and Guardian Genes, p 1049-1080. In DNA Repair and Mutagenesis, Second Edition. ASM Press, Washington, DC. doi: 10.1128/9781555816704.ch30
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Image of Figure 30–13
Figure 30–13

Kaplan-Meier curves of the Asp312Asn polymorphism (A), the Arg399Gln polymorphism (B), and the number of variant alleles from both polymorphisms (C). An increase in the number of variant alleles is associated with higher mortality. (Adapted from reference .)

Citation: Errol C, Graham C, Wolfram S, Richard D, Roger A, Tom E. 2006. DNA Polymorphisms in Gatekeeper and Guardian Genes, p 1049-1080. In DNA Repair and Mutagenesis, Second Edition. ASM Press, Washington, DC. doi: 10.1128/9781555816704.ch30
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Image of Figure 30–14
Figure 30–14

Luciferase (LUC) activities by Lys751Gln genotypes. Subjects homozygous for the Gln751 allele show a lower mean DNA repair capacity (as indicated by the horizontal line) than do wild-type Lys751 or heterozygous individuals. Significant scatter among data points is seen. (Adapted from reference .)

Citation: Errol C, Graham C, Wolfram S, Richard D, Roger A, Tom E. 2006. DNA Polymorphisms in Gatekeeper and Guardian Genes, p 1049-1080. In DNA Repair and Mutagenesis, Second Edition. ASM Press, Washington, DC. doi: 10.1128/9781555816704.ch30
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Assessment of the DNA repair activity of an cDNA, deleted for exon 12 using a host cell reactivation assay. (A) Increased expression of luciferase activity in cells was seen following cotransfection of full-length cDNA expression vector but was not seen on cotransfection with the cDNA expression vector with a deletion of exon 12 (p-XPC-deletion Ex12) or with the empty vector (pcDNA3). (B) Reduction in the expression of luciferase in normal cells was seen by cotransfection with an cDNA expression vector with a deletion of exon 12. (Adapted from reference .)

Citation: Errol C, Graham C, Wolfram S, Richard D, Roger A, Tom E. 2006. DNA Polymorphisms in Gatekeeper and Guardian Genes, p 1049-1080. In DNA Repair and Mutagenesis, Second Edition. ASM Press, Washington, DC. doi: 10.1128/9781555816704.ch30
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References

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1. Abdel–Rahman, S. Z.,, W. A. Anwar,, W. E. Abdel–Aal,, H. M. Mostafa, and, W. W. Au. 1998. GSTM1 and GSTT1 genes are potential risk modifiers for bladder cancer. Cancer Detect. Prev. 22:129138.
2. Abdel–Rahman, S. Z., and, R. A. El–Zein. 2000. The 399Gln polymorphism in the DNA repair gene XRCC1 modulates the genotoxic response induced in human lymphocytes by the tobacco–specific nitrosamine NNK. Cancer Lett. 159:6371.
3. Affatato, A. A.,, K. J. Wolfe,, M. S. Lopez,, C. Hallberg,, M. M. Ammenheuser, and, S. Z. Abdel–Rahman. 2004. Effect of XPD/ERCC2 polymorphisms on chromosome aberration frequencies in smokers and on sensitivity to the mutagenic tobacco–specific nitrosamine NNK. Environ. Mol. Mutagen. 44:6573.
4. Agirre, X.,, J. L. Vizmanos,, M. J. Calasanz,, M. Garcia–Delgado,, M. J. Larrayoz, and, F. J. Novo. 2003. Methylation of CpG dinucleotides and/or CCWGG motifs at the promoter of TP53 correlates with decreased gene expression in a subset of acute lymphoblastic leukemia patients. Oncogene 22:10701072.
5. Alcalay, J.,, S. E. Freeman,, L. H. Goldberg, and, J. E. Wolf. 1990. Excision repair of pyrimidine dimers induced by simulated solar radiation in the skin of patients with basal cell carcinoma. J. Investig. Dermatol. 95:506509.
6. Alexandrov, K.,, I. Cascorbi,, M. Rojas,, G. Bouvier,, E. Kriek, and, H. Bartsch. 2002. CYP1A1 and GSTM1 genotypes affect benzo[a]pyrene DNA adducts in smokers’ lung: comparison with aromatic/hydrophobic adduct formation. Carcinogenesis 23:19691977.
7. Andreassen, C. N.,, J. Alsner,, M. Overgaard, and, J. Overgaard. 2003. Prediction of normal tissue radiosensitivity from polymorphisms in candidate genes. Radiother. Oncol. 69:127135.
8. Athas, W. F.,, M. A. Hedayati,, G. M. Matanoski,, E. R. Farmer, and, L. Grossman. 1991. Development and field–test validation of an assay for DNA repair in circulating human lymphocytes. Cancer Res. 51:57865793.
9. Athma, P.,, R. Rappaport, and, M. Swift. 1996. Molecular genotyping shows that ataxia–telangiectasia heterozygotes are predisposed to breast cancer. Cancer Genet. Cytogenet. 92:130134.
10. Au, W. W.,, H. Y. Oh,, J. Grady,, S. A. Salama, and, M. Y. Heo. 2001. Usefulness of genetic susceptibility and biomarkers for evaluation of environmental health risk. Environ. Mol. Mutagen. 37:215225.
11. Au, W. W.,, S. A. Salama, and, C. H. Sierra–Torres. 2003. Functional characterization of polymorphisms in DNA repair genes using cytogenetic challenge assays. Environ. Health Perspect. 111:18431850.
12. Baccarelli, A.,, D. Calista,, P. Minghetti,, B. Marinelli,, B. Albetti,, T. Tseng,, M. Hedayati,, L. Grossman,, G. Landi,, J. P. Struewing, and, M. T. Landi. 2004. XPD gene polymorphism and host characteristics in the association with cutaneous malignant melanoma risk. Br. J. Cancer 90:497502.
13. Baranovskaya, S.,, J. L. Soto,, M. Perucho, and, S. R. Malkhosyan. 2001. Functional significance of concomitant inactivation of hMLH1 and hMSH6 in tumor cells of the microsatellite mutator phenotype. Proc. Natl. Acad. Sci. USA 98:1510715112.
14. Barquinero, J. F.,, L. Barrios,, M. Ribas,, J. Egozcue, and, M. R. Caballin. 2001. Cytogenetic sensitivity of three Fanconi anemia heterozygotes to bleomycin and ionizing radiation. Cancer Genet. Cytogenet. 124:8083.
15. Bartsch, H.,, U. Nair,, A. Risch,, M. Rojas,, H. Wikman, and, K. Alexandrov. 2000. Genetic polymorphism of CYP genes, alone or in combination, as a risk modifier of tobacco–related cancers. Cancer Epidemiol. Bio–markers Prev. 9:328.
16. Bernardini, S.,, A. Hirvonen,, H. Jarventaus, and, H. Norppa. 2002. Influence of GSTM1 and GSTT1 genotypes on sister chromatid exchange induction by styrene in cultured human lymphocytes. Carcinogenesis 23:893897.
17. Berwick, M., and, P. Vineis. 2000. Markers of DNA repair and susceptibility to cancer in humans: an epidemiologic review. J. Natl. Cancer Inst. 92:874897.
18. Blandino, G.,, A. J. Levine, and, M. Oren. 1999. Mutant p53 gain of function: differential effects of different p53 mutants on resistance of cultured cells to chemotherapy. Oncogene 18:477485.
19. Boley, S. E.,, E. E. Anderson,, J. E. French,, L. A. Donehower,, D. B. Walker, and, L. Recio. 2000. Loss of p53 in benzene–induced thymic lymphomas in p53+/ mice: evidence of chromosomal recombination. Cancer Res. 60:28312835.
20. Bondy, M. L.,, A. P. Kyritsis,, J. Gu,, M. de Andrade,, J. Cunningham,, V. A. Levin,, J. M. Bruner, and, Q. Wei. 1996. Mutagen sensitivity and risk of gliomas: a case–control analysis. Cancer Res. 56:14841486.
21. Bondy, M. L.,, M. R. Spitz,, S. Halabi,, J. J. Fueger,, S. P. Schantz,, D. Sample, and, T. C. Hsu. 1993. Association between family history of cancer and mutagen sensitivity in upper aerodigestive tract cancer patients. Cancer Epidemiol. Biomarkers Prev. 2:103106.
22. Borgaonkar, D. S.,, L. C. Schmidt,, S. E. Martin,, M. D. Kanzer,, L. Edelsohn,, J. Growdon, and, L. A. Farrer. 1993. Linkage of late–onset Alzheimer’s disease with apolipoprotein E type 4 on chromosome 19. Lancet 342:625.
23. Borresen, A. L.,, T. I. Andersen,, S. Tretli,, A. Heiberg, and, P. Moller. 1990. Breast cancer and other cancers in Norwegian families with ataxia–telangiectasia. Genes Chromosomes Cancer 2:339340.
24. Brodie, A.,, B. Long, and, Q. Lu. 1998. Aromatase expression in the human breast. Breast Cancer Res. Treat. 49(Suppl. 1):S85S91; discussion, S109S119.
25. Broeks, A.,, J. H. Urbanus,, A. N. Floore,, E. C. Dahler,, J. G. Klijn,, E. J. Rutgers,, P. Devilee,, N. S. Russell,, F. E. van Leeuwen, and, L. J. van’t Veer. 2000. ATM–heterozygous germline mutations contribute to breast cancer–susceptibility. Am. J. Hum. Genet. 66:494500.
26. Butkiewicz, D.,, K. J. Cole,, D. H. Phillips,, C. C. Harris, and, M. Chorazy. 1999. GSTM1, GSTP1, CYP1A1 and CYP2D6 polymorphisms in lung cancer patients from an environmentally polluted region of Poland: correlation with lung DNA adduct levels. Eur. J. Cancer Prev. 8:315323.
27. Butkiewicz, D.,, E. Grzybowska,, K. Hemminki,, S. Ovrebo,, A. Haugen,, G. Motykiewicz, and, M. Chorazy. 1998. Modulation of DNA adduct levels in human mononuclear white blood cells and granulocytes by CYP1A1 CYP2D6 and GSTM1 genetic polymorphisms. Mutat. Res. 415:97108.
28. Butkiewicz, D.,, E. Grzybowska,, D. H. Phillips,, K. Hemminki, and, M. Chorazy. 2000. Polymorphisms of the GSTP1 and GSTM1 genes and PAH–DNA adducts in human mononuclear white blood cells. Environ. Mol. Mutagen. 35:99105.
29. Butkiewicz, D.,, M. Rusin,, L. Enewold,, P. G. Shields,, M. Chorazy, and, C. C. Harris. 2001. Genetic polymorphisms in DNA repair genes and risk of lung cancer. Carcinogenesis 22:593597.
30. Caporaso, N. E., 2002. Why have we failed to find the low penetrance genetic constituents of common cancers? Cancer Epidemiol. Biomarkers Prev. 11:15441549.
31. Carere, A.,, C. Andreoli,, R. Galati,, P. Leopardi,, F. Marcon,, M. V. Rosati,, S. Rossi,, F. Tomei,, A. Verdina,, A. Zijno, and, R. Crebelli. 2002. Biomonitoring of exposure to urban air pollutants: analysis of sister chromatid exchanges and DNA lesions in peripheral lymphocytes of traffic policemen. Mutat. Res. 518:215224.
32. Casse, C.,, Y. C. Hu, and, S. A. Ahrendt. 2003. The XRCC1 codon 399 Gln allele is associated with adenine to guanine p53 mutations in non–small cell lung cancer. Mutat. Res. 528:1927.
33. Chen, J.,, G. G. Birkholtz,, P. Lindblom,, C. Rubio, and, A. Lindblom. 1998. The role of ataxia–telangiectasia heterozygotes in familial breast cancer. Cancer Res. 58:13761379.
34. Chen, L.,, A. Elahi,, J. Pow–Sang,, P. Lazarus, and, J. Park. 2003. Association between polymorphism of human oxoguanine glycosylase 1 and risk of prostate cancer. J. Urol. 170:24712474.
35. Chen, P.,, J. Wiencke,, K. Aldape,, A. Kesler–Diaz,, R. Miike,, K. Kelsey,, M. Lee,, J. Liu, and, M. Wrensch. 2000. Association of an ERCC1 polymorphism with adult–onset glioma. Cancer Epidemiol. Biomarkers Prev. 9:843847.
36. Chen, S.,, D. Tang,, K. Xue,, L. Xu,, G. Ma,, Y. Hsu, and, S. S. Cho. 2002. DNA repair gene XRCC1 and XPD polymorphisms and risk of lung cancer in a Chinese population. Carcinogenesis 23:13211325.
37. Chenevix–Trench, G.,, A. B. Spurdle,, M. Gatei,, H. Kelly,, A. Marsh,, X. Chen,, K. Donn,, M. Cummings,, D. Nyholt,, M. A. Jenkins,, C. Scott,, G. M. Pupo,, T. Dork,, R. Bendix,, J. Kirk,, K. Tucker,, M. R. McCredie,, J. L. Hopper,, J. Sambrook,, G. J. Mann, et al., 2002. Dominant negative ATM mutations in breast cancer families. J. Natl. Cancer Inst. 94:205215.
38. Cheng, L.,, S. A. Eicher,, Z. Guo,, W. K. Hong,, M. R. Spitz, and, Q. Wei. 1998. Reduced DNA repair capacity in head and neck cancer patients. Cancer Epidemiol. Biomarkers Prev. 7:465468.
39. Cheng, T. J.,, D. C. Christiani,, J. K. Wiencke,, J. C. Wain,, X. Xu, and, K. T. Kelsey. 1995. Comparison of sister chromatid exchange frequency in peripheral lymphocytes in lung cancer cases and controls. Mutat. Res. 348:7582.
40. Cheo, D. L.,, L. B. Meira,, D. K. Burns,, A. M. Reis,, T. Issac, and, E. C. Friedberg. 2000. Ultraviolet B radiation–induced skin cancer in mice defective in the Xpc, Trp53, and Apex (HAP1) genes: genotype–specific effects on cancer predisposition and pathology of tumors. Cancer Res. 60:15801584.
41. Cherry, L. M., and, T. C. Hsu. 1983. Bleomycin–induced chromosome damage in lymphocytes of medullary thyroid carcinoma patients and their family members. Anticancer Res. 3:367372.
42. Cho, E. Y.,, A. Hildesheim,, C. J. Chen,, M. M. Hsu,, I. H. Chen,, B. F. Mittl,, P. H. Levine,, M. Y. Liu,, J. Y. Chen,, L. A. Brinton,, Y. J. Cheng, and, C. S. Yang. 2003. Nasopharyngeal carcinoma and genetic polymorphisms of DNA repair enzymes XRCC1 and hOGG1. Cancer Epidemiol. Bio–markers Prev. 12:11001104.
43. Cleary, S. P.,, W. Zhang,, N. Di Nicola,, M. Aronson,, J. Aube,, A. Steinman,, R. Haddad,, M. Redston,, S. Gallinger,, S. A. Narod, and, R. Gryfe. 2003. Heterozygosity for the BLM(Ash) mutation and cancer risk. Cancer Res. 63:17691771.
44. Cloos, J.,, V. Bongers,, H. Lubsen,, H. Tobi,, B. J. Braakhuis, and, G. B. Snow. 1996. Lack of effect of daily N –acetylcysteine supplementation on mutagen sensitivity. Cancer Epidemiol. Biomarkers Prev. 5:941944.
45. Cloos, J.,, B. J. Braakhuis,, I. Steen,, M. P. Copper,, N. de Vries,, J. J. Nauta, and, G. B. Snow. 1994. Increased mutagen sensitivity in head–and–neck squamous–cell carcinoma patients, particularly those with multiple primary tumors. Int. J. Cancer 56:816819.
46. Cloos, J.,, E. J. Nieuwenhuis,, D. I. Boomsma,, D. J. Kuik,, M. L. van der Sterre,, F. Arwert,, G. B. Snow, and, B. J. Braakhuis. 1999. Inherited susceptibility to bleomycin–induced chromatid breaks in cultured peripheral blood lymphocytes. J. Natl. Cancer Inst. 91:11251130.
47. Cloos, J.,, M. R. Spitz,, S. P. Schantz,, T. C. Hsu,, Z. F. Zhang,, H. Tobi,, B. J. Braakhuis, and, G. B. Snow. 1996. Genetic susceptibility to head and neck squamous cell carcinoma. J. Natl. Cancer Inst. 88:530535.
48. Cloos, J.,, I. Steen,, A. J. Timmerman,, G. P. van der Schans,, G. B. Snow, and, B. J. Braakhuis. 1996. DNA–damage processing in blood lymphocytes of head–and–neck–squamous–cell–carcinoma patients is dependent on tumor site. Int. J. Cancer 68:2629.
49. Collins, F. S.,, L. D. Brooks, and, A. Chakravarti. 1998. A DNA polymorphism discovery resource for research on human genetic variation. Genome Res. 8:12291231.
50. Condie, A.,, R. L. Powles,, C. D. Hudson,, V. Shepherd,, S. Bevan,, M. R. Yuille, and, R. S. Houlston. 2002. Analysis of the Fanconi anaemia complementation group A gene in acute myeloid leukaemia. Leuk. Lym– phoma 43:18491853.
51. Conforti–Froes, N.,, R. el–Zein,, S. Z. Abdel–Rahman,, J. B. Zwischenberger, and, W. W. Au. 1997. Predisposing genes and increased chromosome aberrations in lung cancer cigarette smokers. Mutat. Res. 379:5359.
52. Cook, W. D., and, B. J. McCaw. 2000. Accommodating haploinsufficient tumor suppressor genes in Knudson’s model. Oncogene 19:34343438.
53. Corder, E. H.,, A. M. Saunders,, W. J. Strittmatter,, D. E. Schmechel,, P. C. Gaskell,, G. W. Small,, A. D. Roses,, J. L. Haines, and, M. A. Pericak–Vance. 1993. Gene dose of apolipoprotein E type 4 allele and the risk of Alzheimer’s disease in late onset families. Science 261:921923.
54. Cortessis, V.,, S. Ingles,, R. Millikan,, A. Diep,, R. A. Gatti,, L. Richardson,, W. D. Thompson,, A. Paganini–Hill,, R. S. Sparkes, and, R. W. Haile. 1993. Linkage analysis of DRD2, a marker linked to the ataxia–telangiectasia gene, in 64 families with premenopausal bilateral breast cancer. Cancer Res. 53:50835086.
55. Cosma, G.,, F. Crofts,, E. Taioli,, P. Toniolo, and, S. Garte. 1993. Relationship between genotype and function of the human CYP1A1 gene. J. Toxicol. Environ. Health 40:309316.
56. David–Beabes, G. L.,, R. M. Lunn, and, S. J. London. 2001. No association between the XPD (Lys751G1n) polymorphism or the XRCC3 (Thr241Met) polymorphism and lung cancer risk. Cancer Epidemiol. Bio–markers Prev. 10:911912.
57. Deeb, S. S.,, L. Fajas,, M. Nemoto,, J. Pihlajamaki,, L. Mykkanen,, J. Kuusisto,, M. Laakso,, W. Fujimoto, and, J. Auwerx. 1998. A Pro12Ala substitution in PPARgamma2 associated with decreased receptor activity, lower body mass index and improved insulin sensitivity. Nat. Genet. 20:284287.
58. de Koning, J. P.,, J. H. Mao, and, A. Balmain. 2003. Novel approaches to identify low–penetrance cancer susceptibility genes using mouse models. Recent Results Cancer Res. 163:1927; discussion 264266.
59. de Vries, A.,, E. R. Flores,, B. Miranda,, H. M. Hsieh,, C. T. van Oostrom,, J. Sage, and, T. Jacks. 2002. Targeted point mutations of p53 lead to dominant–negative inhibition of wild–type p53 function. Proc. Natl. Acad. Sci. USA 99:29482953.
60. Di Como, C. J.,, C. Gaiddon, and, C. Prives. 1999. p73 function is inhibited by tumor–derived p53 mutants in mammalian cells. Mol. Cell. Biol. 19:14381449.
61. Divine, K. K.,, F. D. Gilliland,, R. E. Crowell,, C. A. Stidley,, T. J. Bocklage,, D. L. Cook, and, S. A. Belinsky. 2001. The XRCC1 399 glutamine allele is a risk factor for adenocarcinoma of the lung. Mutat. Res. 461:273278.
62. Djuzenova, C. S.,, A. Rothfuss,, U. Oppitz,, G. Spelt,, D. Schindler,, H. Hoehn, and, M. Flentje. 2001. Response to X–irradiation of Fanconi anemia homozygous and heterozygous cells assessed by the single–cell gel electrophoresis (comet) assay. Lab. Investig. 81:185192.
63. Donahue, R. P.,, W. B. Bias,, J. H. Renwick, and, V. A. McKusick. 1968. Probable assignment of the Duffy blood group locus to chromosome 1 in man. Proc. Natl. Acad. Sci. USA 61:949955.
64. Duell, E. J.,, R. C. Millikan,, G. S. Pittman,, S. Winkel,, R. M. Lunn,, C. K. Tse,, A. Eaton,, H. W. Mohrenweiser,, B. Newman, and, D. A. Bell. 2001. Polymorphisms in the DNA repair gene XRCC1 and breast cancer. Cancer Epidemiol. Biomarkers Prev. 10:217222.
65. Duell, E. J.,, J. K. Wiencke,, T. J. Cheng,, A. Varkonyi,, Z. F. Zuo,, T. D. Ashok,, E. J. Mark,, J. C. Wain,, D. C. Christiani, and, K. T. Kelsey. 2000. Polymorphisms in the DNA repair genes XRCC1 and ERCC2 and bio–markers of DNA damage in human blood mononuclear cells. Carcinogenesis 21:965971.
66. Dybdahl, M.,, U. Vogel,, G. Frentz,, H. Wallin, and, B. A. Nexo. 1999. Polymorphisms in the DNA repair gene XPD: correlations with risk and age at onset of basal cell carcinoma. Cancer Epidemiol. Biomarkers Prev. 8:7781.
67. Easton, D. F., 1994. Cancer risks in A–T heterozygotes. Int. J. Radiat. Biol. 66:S177182.
68. Easton, D. F.,, J. Peto, and, A. G. Babiker. 1991. Floating absolute risk: an alternative to relative risk in survival and case–control analysis avoiding an arbitrary reference group. Stat. Med. 10:10251035.
69. el–Zein, R.,, N. Conforti–Froes, and, W. W. Au. 1997. Interactions between genetic predisposition and environmental toxicants for development of lung cancer. Environ. Mol. Mutagen. 30:196204.
70. Emmert, S.,, T. D. Schneider,, S. G. Khan, and, K. H. Kraemer. 2001. The human XPG gene: gene architecture, alternative splicing and single nucleotide polymorphisms. Nucleic Acids Res. 29:14431452.
71. Esteller, M., and, J. G. Herman. 2002. Cancer as an epigenetic disease: DNA methylation and chromatin alterations in human tumours. J. Pathol. 196:17.
72. Faham, M.,, S. Baharloo,, S. Tomitaka,, J. DeYoung, and, N. B. Freimer. 2001. Mismatch repair detection (MRD): high–throughput scanning for DNA variations. Hum. Mol. Genet. 10:16571664.
73. Filiadis, I. F.,, I. Georgiou,, Y. Alamanos,, V. Kranas,, X. Giannakopoulos, and, D. Lolis. 1999. Genotypes of N –acetyltransferase–2 and risk of bladder cancer: a case–control study. J. Urol. 161:16721675.
74. FitzGerald, M. G.,, J. M. Bean,, S. R. Hegde,, H. Unsal,, D. J. Mac– Donald,, D. P. Harkin,, D. M. Finkelstein,, K. J. Isselbacher, and, D. A. Haber. 1997. Heterozygous ATM mutations do not contribute to early onset of breast cancer. Nat. Genet. 15:307310.
75. Fodde, R., and, R. Smits. 2002. Cancer biology. A matter of dosage. Science 298:761763.
76. French, J.,, R. D. Storer, and, L. A. Donehower. 2001. The nature of the heterozygous Trp53 knockout model for identification of mutagenic carcinogens. Toxicol. Pathol. 29(Suppl.):2429.
77. French, J. E.,, G. D. Lacks,, C. Trempus,, J. K. Dunnick,, J. Foley,, J. Mahler,, R. R. Tice, and, R. W. Tennant. 2001. Loss of heterozygosity frequency at the Trp53 locus in p53–deficient (+ / —) mouse tumors is carcinogen– and tissue–dependent. Carcinogenesis 22:99106.
78. Friedberg, E. C., 2001. How nucleotide excision repair protects against cancer. Nat. Rev. Cancer 1:2233.
79. Fu, Y. P.,, J. C. Yu,, T. C. Cheng,, M. A. Lou,, G. C. Hsu,, C. Y. Wu,, S. T. Chen,, H. S. Wu,, P. E. Wu, and, C. Y. Shen. 2003. Breast cancer risk associated with genotypic polymorphism of the nonhomologous end–joining genes: a multigenic study on cancer susceptibility. Cancer Res. 63:24402446.
80. Galmarini, C. M.,, N. Falette,, E. Tabone,, C. Levrat,, R. Britten,, N. Voorzanger–Rousselot,, O. Roesch–Gateau,, A. Vanier–Viornery,, A. Puisieux, and, C. Dumontet. 2001. Inactivation of wild–type p53 by a dominant negative mutant renders MCF–7 cells resistant to tubulin–binding agent cytotoxicity. Br. J. Cancer 85:902908.
81. Gao, W. M.,, M. Romkes,, R. D. Day,, J. M. Siegfried,, J. D. Luketich,, H. H. Mady,, M. F. Melhem, and, P. Keohavong. 2003. Association of the DNA repair gene XPD Asp312Asn polymorphism with p53 gene mutations in tobacco–related non–small cell lung cancer. Carcinogenesis 24:16711676.
82. Garte, S.,, L. Gaspari,, A. K. Alexandrie,, C. Ambrosone,, H. Autrup,, J. L. Autrup,, H. Baranova,, L. Bathum,, S. Benhamou,, P. Boffetta,, C. Bouchardy,, K. Breskvar,, J. Brockmoller,, I. Cascorbi,, M. L. Clapper,, C. Coutelle,, A. Daly,, M. Dell’Omo,, V. Dolzan,, C. M. Dresler, et al., 2001. Metabolic gene polymorphism frequencies in control populations. Cancer Epidemiol. Biomarkers Prev. 10:12391248.
83. Gatti, R. A.,, I. Berkel,, E. Boder,, G. Braedt,, P. Charmley,, P. Con– cannon,, F. Ersoy,, T. Foroud,, N. G. Jaspers,, K. Lange,, G. M. Lathrop,, M. Leppert,, Y. Nakamura,, P. Oconnell,, M. Paterson,, W. Salser,, O. Sanal,, J. Silver,, R. S. Sparkes,, E. Susi, et al., 1988. Localization of an ataxia–telangiectasia gene to chromosome 11q22–23. Nature 336:577580.
84. Gatti, R. A.,, A. Tward, and, P. Concannon. 1999. Cancer risk in ATM heterozygotes: a model of phenotypic and mechanistic differences between missense and truncating mutations. Mol. Genet. Metab. 68:419423.
85. German, J.,, D. Bloom, and, E. Passarge. 1977. Bloom’s syndrome. V. Surveillance for cancer in affected families. Clin. Genet. 12:162168.
86. Gerstman, B. B., 2003. Epidemiology Kept Simple: an Introduction to Traditional and Modern Epidemiology, 2nd ed. Wiley–Liss, Inc., New York, N.Y.
87. Godschalk, R. W.,, J. W. Dallinga,, H. Wikman,, A. Risch,, J. C. Kleinjans,, H. Bartsch, and, F. J. Van Schooten. 2001. Modulation of DNA and protein adducts in smokers by genetic polymorphisms in GSTM1,GSTT1, NAT1 and NAT2. Pharmacogenetics 11:389398.
88. Godschalk, R. W.,, J. U. Ostertag,, A. M. Zandsteeg,, B. Van Agen,, H. A. Neuman,, H. Van Straaten, and, F. J. Van Schooten. 2001. Impact of GSTM1 on aromatic–DNA adducts and p53 accumulation in human skin and lymphocytes. Pharmacogenetics 11:537543.
89. Gonzalez, F. J.,, F. Vilbois,, J. P. Hardwick,, O. W. McBride,, D. W. Nebert,, H. V. Gelboin, and, U. A. Meyer. 1988. Human debrisoquine 4–hydroxylase (P450IID1): cDNA and deduced amino acid sequence and assignment of the CYP2D locus to chromosome 22. Genomics 2:174179.
90. Goode, E. L.,, C. M. Ulrich, and, J. D. Potter. 2002. Polymorphisms in DNA repair genes and associations with cancer risk. Cancer Epidemiol. Bio–markers Prev. 11:15131530.
91. Goss, P. E., and, K. Strasser. 2001. Aromatase inhibitors in the treatment and prevention of breast cancer. J. Clin. Oncol. 19:881894.
92. Gottlieb, E.,, R. Haffner,, A. King,, G. Asher,, P. Gruss,, P. Lonai, and, M. Oren. 1997. Transgenic mouse model for studying the transcriptional activity of the p53 protein: age– and tissue–dependent changes in radiation–induced activation during embryogenesis. EMBO J. 16:13811390.
93. Gruber, S. B.,, N. A. Ellis,, K. K. Scott,, R. Almog,, P. Kolachana,, J. D. Bonner,, T. Kirchhoff,, L. P. Tomsho,, K. Nafa,, H. Pierce,, M. Low,, J. Satagopan,, H. Rennert,, H. Huang,, J. K. Greenson,, J. Groden,, B. Rapaport,, J. R. Shia,, S. Johnson,, P. K. Gregersen, et al., 2002. BLM heterozygosity and the risk of colorectal cancer. Science 297:2013.
94. Gurubhagavatula, S.,, G. Liu,, S. Park,, W. Zhou,, L. Su,, J. C. Wain,, T. J. Lynch,, D. S. Neuberg, and, D. C. Christiani. 2004. XPD and XRCC1 genetic polymorphisms are prognostic factors in advanced non–small–cell lung cancer patients treated with platinum chemotherapy. J. Clin. Oncol. 22:25942601.
95. Haiman, C. A.,, S. E. Hankinson,, D. Spiegelman,, I. De Vivo,, G. A. Colditz,, W. C. Willett,, F. E. Speizer, and, D. J. Hunter. 2000. A tetranu– cleotide repeat polymorphism in CYP19 and breast cancer risk. Int. J. Cancer 87:204210.
96. Haiman, C. A.,, D. O. Stram,, M. C. Pike,, L. N. Kolonel,, N. P. Burtt,, D. Altshuler,, J. Hirschhorn, and, B. E. Henderson. 2003. A comprehensive haplotype analysis of CYP19 and breast cancer risk: the Multiethnic Cohort. Hum. Mol. Genet. 12:26792692.
97. Hall, J.,, D. R. English,, M. Artuso,, B. K. Armstrong, and, M. Winter. 1994. DNA repair capacity as a risk factor for non–melanocytic skin cancer—a molecular epidemiological study. Int. J. Cancer 58:179184.
98. Hall, J. M.,, M. K. Lee,, B. Newman,, J. E. Morrow,, L. A. Anderson,, B. Huey, and, M. C. King. 1990. Linkage of early–onset familial breast cancer to chromosome 17q21. Science 250:16841689.
99. Hamajima, N.,, T. Saito,, K. Matsuo,, T. Suzuki,, T. Nakamura,, A. Matsuura,, K. Okuma, and, K. Tajima. 2002. Genotype frequencies of 50 polymorphisms for 241 Japanese non–cancer patients. J. Epidemiol. 12:229236.
100. Hamajima, N.,, T. Takezaki, and, K. Tajima. 2002. Allele frequencies of 25 polymorphisms pertaining to cancer risk for Japanese, Koreans and Chinese. Asian. Pac. J. Cancer Prev. 3:197206.
101. Han, J.,, G. A. Colditz,, L. D. Samson, and, D. J. Hunter. 2004. Polymorphisms in DNA double–strand break repair genes and skin cancer risk. Cancer Res. 64:30093013.
102. Han, J.,, S. E. Hankinson,, I. De Vivo,, D. Spiegelman,, R. M. Tamimi,, H. W. Mohrenweiser,, G. A. Colditz, and, D. J. Hunter. 2003. A prospective study of XRCC1 haplotypes and their interaction with plasma carotenoids on breast cancer risk. Cancer Res. 63:85368541.
103. Hao, B.,, H. Wang,, K. Zhou,, Y. Li,, X. Chen,, G. Zhou,, Y. Zhu,, X. Miao,, W. Tan,, Q. Wei,, D. Lin, and, F. He. 2004. Identification of genetic variants in base excision repair pathway and their associations with risk of esophageal squamous cell carcinoma. Cancer Res. 64:43784384.
104. Harms, C.,, S. A. Salama,, C. H. Sierra–Torres,, N. Cajas–Salazar, and, W. W. Au. 2004. Polymorphisms in DNA repair genes, chromosome aberrations, and lung cancer. Environ. Mol. Mutagen. 44:7482.
105. Harris, H., 1980. The Principles of Human Genetic Variation, 3rd ed. Elsevier/North–Holland Press, Amsterdam, The Netherlands.
106. Hayashi, S.,, J. Watanabe, and, K. Kawajiri. 1992. High susceptibility to lung cancer analyzed in terms of combined genotypes of P450IA1 and Mu–class glutathione S–transferase genes. Jpn. J. Cancer Res. 83:866870.
107. Healey, C. S.,, A. M. Dunning,, F. Durocher,, D. Teare,, P. D. Pharoah,, R. N. Luben,, D. F. Easton, and, B. A. Ponder. 2000. Polymorphisms in the human aromatase cytochrome P450 gene (CYP19) and breast cancer risk. Carcinogenesis 21:189193.
108. Healey, C. S.,, A. M. Dunning,, M. D. Teare,, D. Chase,, L. Parker,, J. Burn,, J. Chang–Claude,, A. Mannermaa,, V. Kataja,, D. G. Huntsman,, P. D. Pharoah,, R. N. Luben,, D. F. Easton, and, B. A. Ponder. 2000. A common variant in BRCA2 is associated with both breast cancer risk and prenatal viability. Nat. Genet. 26:362364.
109. Hein, D. W., 2002. Molecular genetics and function of NAT1 and NAT2: role in aromatic amine metabolism and carcinogenesis. Mutat. Res. 506–507:6577.
110. Hein, D. W., 2000. N –Acetyltransferase genetics and their role in predisposition to aromatic and heterocyclic amine–induced carcinogenesis. Toxicol. Lett. 112–113:349356.
111. Hirvonen, A., 1999. Polymorphic NATs and cancer predisposition. IARCSci. Publ. 1999:251270.
112. Hou, S. M.,, S. Falt,, S. Angelini,, K. Yang,, F. Nyberg,, B. Lambert, and, K. Hemminki. 2002. The XPD variant alleles are associated with increased aromatic DNA adduct level and lung cancer risk. Carcinogenesis 23:599603.
113. Hou, S. M.,, S. Falt,, K. Yang,, F. Nyberg,, G. Pershagen,, K. Hemminki, and, B. Lambert. 2001. Differential interactions between GSTM1 and NAT2 genotypes on aromatic DNA adduct level and HPRT mutant frequency in lung cancer patients and population controls. Cancer Epidemiol. Bio–markers Prev. 10:133140.
114. Hou, S. M.,, C. Ryk,, A. Kannio,, S. Angelini,, S. Falt,, F. Nyberg, and, K. Husgafvel–Pursiainen. 2003. Influence of common XPD and XRCC1 variant alleles on p53 mutations in lung tumors. Environ. Mol. Mutagen. 41:3742.
115. Hsieh, L. L.,, H. T. Chien,, I. H. Chen,, C. T. Liao,, H. M. Wang,, S. M. Jung,, P. F. Wang,, J. T. Chang,, M. C. Chen, and, A. J. Cheng. 2003. The XRCC1 399Gln polymorphism and the frequency of p53 mutations in Taiwanese oral squamous cell carcinomas. Cancer Epidemiol. Biomarkers Prev. 12:439443.
116. Hsu, T. C.,, L. M. Cherry, and, N. A. Samaan. 1985. Differential mutagen susceptibility in cultured lymphocytes of normal individuals and cancer patients. Cancer Genet. Cytogenet. 17:307313.
117. Hsu, T. C.,, L. Feun,, Z. Trizna,, N. Savaraj,, L. R. Shirley,, C. L. Furlong,, S. P. Schantz,, R. S. Weber,, T. J. Shen, and, O. Kucuk. 1993. Differential sensitivity among three human subpopulations in response to 4–nitroquinoline–1–oxide and to bleomycin. Int. J. Oncol. 3:827830.
118. Hsu, T. C.,, D. A. Johnston,, L. M. Cherry,, D. Ramkissoon,, S. P. Schantz,, J. M. Jessup,, R. J. Winn,, L. Shirley, and, C. Furlong. 1989. Sensitivity to genotoxic effects of bleomycin in humans: possible relationship to environmental carcinogenesis. Int. J. Cancer 43:403409.
119. Hu, J. J.,, M. C. Hall,, L. Grossman,, M. Hedayati,, D. L. McCul– lough,, K. Lohman, and, L. D. Case. 2004. Deficient nucleotide excision repair capacity enhances human prostate cancer risk. Cancer Res. 64:11971201.
120. Hu, J. J.,, G. C. Roush,, N. Dubin,, M. Berwick,, D. F. Roses, and, M. N. Harris. 1997. Poly(ADP–ribose) polymerase in human breast cancer: a case–control analysis. Pharmacogenetics 7:309316.
121. Hu, J. J.,, T. R. Smith,, M. S. Miller,, K. Lohman, and, L. D. Case. 2002. Genetic regulation of ionizing radiation sensitivity and breast cancer risk. Environ. Mol. Mutagen. 39:208215.
122. Hu, J. J.,, T. R. Smith,, M. S. Miller,, H. W. Mohrenweiser,, A. Golden, and, L. D. Case. 2001. Amino acid substitution variants of APE1 and XRCC1 genes associated with ionizing radiation sensitivity. Carcinogenesis 22:917922.
123. Hulla, J. E.,, J. E. French, and, J. K. Dunnick. 2001. Chromosome 11 loss from thymic lymphomas induced in heterozygous Trp53 mice by phenolphthalein. Toxicol. Sci. 60:264270.
124. Hung, R. J.,, P. Boffetta,, J. Brockmoller,, D. Butkiewicz,, I. Cascorbi,, M. L. Clapper,, S. Garte,, A. Haugen,, A. Hirvonen,, S. Anttila,, I. Kalina,, L. Le Marchand,, S. J. London,, A. Rannug,, M. Romkes,, J. Salagovic,, B. Schoket,, L. Gaspari, and, E. Taioli. 2003. CYP1A1 and GSTM1 genetic polymorphisms and lung cancer risk in Caucasian non–smokers: a pooled analysis. Carcinogenesis 24:875882.
125. Ide, F.,, M. Kitada,, H. Sakashita, and, K. Kusama. 2003. Reduction of p53 dosage renders mice hypersensitive to 7,12–dimethylbenz(alpha) anthracene–induced salivary gland tumorigenesis. Anticancer Res. 23:201204.
126. Ishibe, N.,, R. Sinha,, D. W. Hein,, M. Kulldorff,, P. Strickland,, A. J. Fretland,, W. H. Chow,, F. F. Kadlubar,, N. P. Lang, and, N. Rothman. 2002. Genetic polymorphisms in heterocyclic amine metabolism and risk of colorectal adenomas. Pharmacogenetics 12:145150.
127. Ito, H.,, K. Matsuo,, N. Hamajima,, T. Mitsudomi,, T. Sugiura,, T. Saito,, T. Yasue,, K. M. Lee,, D. Kang,, K. Y. Yoo,, S. Sato,, R. Ueda, and, K. Tajima. 2004. Gene–environment interactions between the smoking habit and polymorphisms in the DNA repair genes, APE1 Asp148Glu and XRCC1 Arg399Gln, in Japanese lung cancer risk. Carcinogenesis 25:13951401.
128. Itoh, T.,, S. Linn,, R. Kamide,, H. Tokushige,, N. Katori,, Y. Hosaka, and, M. Yamaizumi. 2000. Xeroderma pigmentosum variant heterozygotes show reduced levels of recovery of replicative DNA synthesis in the presence of caffeine after ultraviolet irradiation. J. Investig. Dermatol. 115: 981985.
129. Jacob, S., and, F. Praz. 2002. DNA mismatch repair defects: role in colorectal carcinogenesis. Biochimie 84:2747.
130. Jaloszynski, P.,, M. Kujawski,, M. Czub–Swierczek,, J. Markowska, and, K. Szyfter. 1997. Bleomycin–induced DNA damage and its removal in lymphocytes of breast cancer patients studied by comet assay. Mutat. Res. 385:223233.
131. Jayasena, V. K., and, B. H. Johnston. 1993. Complement–stabilized D–loop. RecA–catalyzed stable pairing of linear DNA molecules at internal sites. J. Mol. Biol. 230:10151024.
132. Jeon, H. S.,, K. M. Kim,, S. H. Park,, S. Y. Lee,, J. E. Choi,, G. Y. Lee,, S. Kam,, R. W. Park,, I. S. Kim,, C. H. Kim,, T. H. Jung, and, J. Y. Park. 2003. Relationship between XPG codon 1104 polymorphism and risk of primary lung cancer. Carcinogenesis 24:16771681.
133. Jerry, D. J.,, J. S. Butel,, L. A. Donehower,, E. J. Paulson,, C. Cochran,, R. W. Wiseman, and, D. Medina. 1994. Infrequent p53 mutations in 7,12–dimethylbenz[a]anthracene–induced mammary tumors in BALB/c and p53 hemizygous mice. Mol. Carcinog. 9:175183.
134. Jiricny, J., 1994. Colon cancer and DNA repair: have mismatches met their match? Trends Genet. 10:164168.
135. Kadouri, L.,, Z. Kote–Jarai,, A. Hubert,, F. Durocher,, D. Abeliovich,, B. Glaser,, T. Hamburger,, R. A. Eeles, and, T. Peretz. 2004. A sin–gle–nucleotide polymorphism in the RAD51 gene modifies breast cancer risk in BRCA2 carriers, but not in BRCA1 carriers or noncarriers. Br. J. Cancer 90:20022005.
136. Kang, D., 2003. Genetic polymorphisms and cancer susceptibility of breast cancer in Korean women. J. Biochem. Mol. Biol. 36:2834.
137. Khan, S. G.,, V. Muniz–Medina,, T. Shahlavi,, C. C. Baker,, H. Inui,, T. Ueda,, S. Emmert,, T. D. Schneider, and, K. H. Kraemer. 2002. The human XPC DNA repair gene: arrangement, splice site information content and influence of a single nucleotide polymorphism in a splice acceptor site on alternative splicing and function. Nucleic Acids Res. 30:36243631.
138. Kiffmeyer, W. R.,, E. Langer,, S. M. Davies,, J. Envall,, L. L. Robison, and, J. A. Ross. 2004. Genetic polymorphisms in the Hmong population: implications for cancer etiology and survival. Cancer 100:411417.
139. Kim, M. K.,, S. Zitzmann,, F. Westermann,, K. Arnold,, S. Brouwers,, M. Schwab, and, L. Savelyeva. 2004. Increased rates of spontaneous sister chromatid exchange in lymphocytes of BRCA2+/– carriers of familial breast cancer clusters. Cancer Lett. 210:8594.
140. King, R. C., and, W. D. Stansfield. 1990. Dictionary of Genetics. Oxford University Press, Oxford, United Kingdom.
141. Knowlton, R. G.,, O. Cohen–Haguenauer,, N. Van Cong,, J. Frezal,, V. A. Brown,, D. Barker,, J. C. Braman,, J. W. Schumm,, L. C. Tsui, and, M. Buchwald. 1985. A polymorphic DNA marker linked to cystic fibrosis is located on chromosome 7. Nature 318:380382.
142. Knudsen, L. E.,, S. H. Loft, and, H. Autrup. 2001. Risk assessment: the importance of genetic polymorphisms in man. Mutat. Res. 482:8388.
143. Kote–Jarai, Z.,, R. D. Williams,, N. Cattini,, M. Copeland,, I. Giddings,, R. Wooster,, R. H. tePoele,, P. Workman,, B. Gusterson,, J. Peacock,, G. Gui,, C. Campbell, and, R. Eeles. 2004. Gene expression profiling after radiation–induced DNA damage is strongly predictive of BRCA1 mutation carrier status. Clin. Cancer Res. 10:958963.
144. Kovacs, E.,, T. Hajto, and, K. Hostanska. 1991. Improvement of DNA repair in lymphocytes of breast cancer patients treated with Viscum album extract (Iscador). Eur. J. Cancer 27:16721676.
145. Kovacs, E., and, H. Langemann. 1991. Differences in the kinetics of DNA repair in cancer patients and healthy controls. Oncology 48:312316.
146. Kovacs, E.,, H. Langemann, and, H. Ludwig. 1992. Do chemo– and radiotherapy affect the DNA repair ability of lymphocytes? Arch. Gynecol. Obstet. 251:121126.
147. Kovacs, E.,, D. Stucki,, W. Weber, and, H. Muller. 1986. Impaired DNA–repair synthesis in lymphocytes of breast cancer patients. Eur. J. Cancer Clin. Oncol. 22:863869.
148. Kristensen, V. N.,, T. I. Andersen,, A. Lindblom,, B. Erikstein,, P. Magnus, and, A. L. Borresen–Dale. 1998. A rare CYP19 (aromatase) variant may increase the risk of breast cancer. Pharmacogenetics 8:4348.
149. Kumar, R.,, L. Hoglund,, C. Zhao,, A. Forsti,, E. Snellman, and, K. Hemminki. 2003. Single nucleotide polymorphisms in the XPG gene: determination of role in DNA repair and breast cancer risk. Int. J. Cancer 103:671675.
150. Kyoizumi, S.,, Y. Kusunoki,, T. Seyama,, A. Hatamochi, and, M. Goto. 1998. In vivo somatic mutations in Werner’s syndrome. Hum. Genet. 103:405410.
151. Lange, E.,, A. L. Borresen,, X. Chen,, L. Chessa,, S. Chiplunkar,, P. Concannon,, S. Dandekar,, S. Gerken,, K. Lange,, T. Liang,, C. Mcconville,, J. Polakow,, O. Porras,, G. Rotman,, O. Sanal,, S. Sheikhavandi,, Y. Shiloh,, E. Sobel,, M. Taylor,, M. Telatar, et al., 1995. Localization of an ataxia–telangiectasia gene to an approximately 500–kb interval on chromosome 11q23.1: linkage analysis of 176 families by an international consortium. Am. J. Hum. Genet. 57:112119.
152. Leach, F. S.,, S. J. Elledge,, C. J. Sherr,, J. K. Willson,, S. Markowitz,, K. W. Kinzler, and, B. Vogelstein. 1993. Amplification of cyclin genes in colorectal carcinomas. Cancer Res. 53:19861989.
153. Leach, F. S.,, N. C. Nicolaides,, N. Papadopoulos,, B. Liu,, J. Jen,, R. Parsons,, P. Peltomaki,, P. Sistonen,, L. A. Aaltonen,, M. Nystrom–Lahti, and et al. 1993. Mutations of a mutS homolog in hereditary nonpolyposis colorectal cancer. Cell 75:12151225.
154. Lee, J. M.,, Y. C. Lee,, S. Y. Yang,, P. W. Yang,, S. P. Luh,, C. J. Lee,, C. J. Chen, and, M. T. Wu. 2001. Genetic polymorphisms of XRCC1 and risk of the esophageal cancer. Int. J. Cancer 95:240246.
155. Lee, S. G.,, B. Kim,, J. Choi,, C. Kim,, I. Lee, and, K. Song. 2002. Genetic polymorphisms of XRCC1 and risk of gastric cancer. Cancer Lett. 187:5360.
156. Lei, Y. C.,, S. J. Hwang,, C. C. Chang,, H. W. Kuo,, J. C. Luo,, M. J. Chang, and, T. J. Cheng. 2002. Effects on sister chromatid exchange frequency of polymorphisms in DNA repair gene XRCC1 in smokers. Mutat Res. 519:93101.
157. Le Marchand, L.,, C. Guo,, S. Benhamou,, C. Bouchardy,, I. Cascorbi,, M. L. Clapper,, S. Garte,, A. Haugen,, M. Ingelman–Sundberg,, M. Kihara,, A. Rannug,, D. Ryberg,, I. Stucker,, H. Sugimura, and, E. Taioli. 2003. Pooled analysis of the CYP1A1 exon 7 polymorphism and lung cancer (United States). Cancer Causes Control 14:339346.
158. Leprat, F.,, C. Alapetite,, F. Rosselli,, A. Ridet,, M. Schlumberger,, A. Sarasin,, H. G. Suarez, and, E. Moustacchi. 1998. Impaired DNA repair as assessed by the “comet” assay in patients with thyroid tumors after a history of radiation therapy: a preliminary study. Int. J. Radiat. Oncol. Biol. Phys. 40:10191026.
159. Li, Y.,, M. J. Marion,, A. Rundle, and, P. W. Brandt–Rauf. 2003. A common polymorphism in XRCC1 as a biomarker of susceptibility for chemically induced genetic damage. Biomarkers 8:408414.
160. Liang, G.,, D. Xing,, X. Miao,, W. Tan,, C. Yu,, W. Lu, and, D. Lin. 2003. Sequence variations in the DNA repair gene XPD and risk of lung cancer in a Chinese population. Int. J. Cancer 105:669673.
161. Liu, R.,, W. A. Paxton,, S. Choe,, D. Ceradini,, S. R. Martin,, R. Horuk,, M. E. MacDonald,, H. Stuhlmann,, R. A. Koup, and, N. R. Landau. 1996. Homozygous defect in HIV–1 coreceptor accounts for resistance of some multiply–exposed individuals to HIV–1 infection. Cell 86:367377.
162. Lunn, R. M.,, K. J. Helzlsouer,, R. Parshad,, D. M. Umbach,, E. L. Harris,, K. K. Sanford, and, D. A. Bell. 2000. XPD polymorphisms: effects on DNA repair proficiency. Carcinogenesis 21:551555.
163. Lunn, R. M.,, R. G. Langlois,, L. L. Hsieh,, C. L. Thompson, and, D. A. Bell. 1999. XRCC1 polymorphisms: effects on aflatoxin B1–DNA adducts and glycophorin A variant frequency. Cancer Res. 59:25572561.
164. Lynch, H. T.,, T. C. Smyrk,, P. Watson,, S. J. Lanspa,, J. F. Lynch,, P. M. Lynch,, R. J. Cavalieri, and, C. R. Boland. 1993. Genetics, natural history, tumor spectrum, and pathology of hereditary nonpolyposis colorectal cancer: an updated review. Gastroenterology 104:15351549.
165. Maggiolini, M.,, D. Bonofiglio,, V. Pezzi,, A. Carpino,, S. Marsico,, V. Rago,, A. Vivacqua,, D. Picard, and, S. Ando. 2002. Aromatase overex–pression enhances the stimulatory effects of adrenal androgens on MCF7 breast cancer cells. Mol. Cell. Endocrinol. 193:1318.
166. Markowitz, M. M.,, D. B. Johnson,, R. W. Pero,, S. J. Winawer, and, D. G. Miller. 1988. Effects of cumene hydroperoxide on adenosine diphosphate ribosyl transferase in mononuclear leukocytes of patients with adenomatous polyps in the colon. Carcinogenesis 9:349355.
167. Maroulakou, I. G.,, M. A. Shibata,, C. L. Jorcyk,, X. X. Chen, and, J. E. Green. 1997. Reduced p53 dosage associated with mammary tumor metastases in C3(1)/TAG transgenic mice. Mol. Carcinog. 20:168174.
168. Marra, G.,, S. D’Atri,, C. Corti,, L. Bonmassar,, M. S. Cattaruzza,, P. Schweizer,, K. Heinimann,, Z. Bartosova,, M. Nystrom–Lahti, and, J. Jiricny. 2001. Tolerance of human MSH2 +/– lymphoblastoid cells to the methylating agent temozolomide. Proc. Natl. Acad. Sci. USA 98:71647169.
169. Martin, R. H.,, A. Rademaker, and, J. German. 1994. Chromosomal breakage in human spermatozoa, a heterozygous effect of the Bloom syndrome mutation. Am. J. Hum. Genet. 55:12421246.
170. Mathonnet, G.,, D. Labuda,, C. Meloche,, T. Wambach,, M. Krajinovic, and, D. Sinnett. 2003. Variable continental distribution of polymorphisms in the coding regions of DNA–repair genes. J. Hum. Genet. 48:659664.
171. Matsuo, K.,, N. Hamajima,, R. Suzuki,, M. Andoh,, S. Nakamura,, M. Seto,, Y. Morishimae, and, K. Tajima. 2004. Lack of association between DNA base excision repair gene XRCC1 Gln399Arg polymorphism and risk of malignant lymphoma in Japan. Cancer Genet. Cytogenet. 149:7780.
172. Matta, J. L.,, J. L. Villa,, J. M. Ramos,, J. Sanchez,, G. Chompre,, A. Ruiz, and, L. Grossman. 2003. DNA repair and nonmelanoma skin cancer in Puerto Rican populations. J. Am. Acad. Dermatol. 49:433439.
173. Matullo, G.,, S. Guarrera,, S. Carturan,, M. Peluso,, C. Malaveille,, L. Davico,, A. Piazza, and, P. Vineis. 2001. DNA repair gene polymorphisms, bulky DNA adducts in white blood cells and bladder cancer in a case–control study. Int. J. Cancer 92:562567.