With the vast technological and informational resources increasingly available from investments in “genomics,” toxicology and much of biological science, is faced with previously undreamed of opportunities and equally daunting challenges. The ability to generate the large quantities of data becoming routinely available could not be imagined a decade ago. The complexities of data analysis are increasingly the rate-limiting element in scientific advances. The expectations that these large scientific investments will reduce the incidence of human disease and improve health are very high. An emphasis on genetic variation and Toxicogenetics is expected to yield risk estimates for specific rather than average individuals and individuals with varied lifestyles and complex patterns of exposure. Examples from studies of polymorphic variation in DNA repair genes in the healthy population and cancer risk highlight the complexity and challenges of incorporating genetic variation into quantitative estimates of risk associated with environmentally relevant exposures. Similar issues exist in selecting the animal models most appropriate for predicting human risk from environmental exposures to toxic agents.
Bernstein, C., Bernstein, H., Payne, C.M., and Garewal, H. (2002). DNA repair/pro-apoptotic dual-role proteins in five major DNA repair pathways: fail-safe protection against carcinogenesis . Mutat Res511, 145—78.
6.
Berwick, M., Matullo, G., and Vineis, P. (2002). Studies of DNA repair and human cancer: an update . In Biomarkers of Environmentally Associated Disease: Technologies, Concepts and Perspectives (S. H. Wilson and W. A. Suk, eds.), pp. 84—105. Lewis Publishers, Boca Raton, Florida.
7.
Berwick, M., and Vineis, P. (2000). Markers of DNA repair and susceptibility to cancer in humans: an epidemiologic review. J Natl Cancer Inst92, 874—97.
8.
Bigbee, W.L., Fuscoe, J.C., Grant, S.G., Jones, I.M., Gorvad, A.E., Harrington-Brock, K., Strout, C.L., Thomas, C.B., and Moore, M.M. (1998). Human in vivo somatic mutation measured at two loci: individuals with stably elevated background erythrocyte glycophorin A (GPA) variant frequencies exhibit normal T lymphocyte hprt mutant frequencies . Mutat Res397, 119— 36.
9.
Bonassi, S., Hagmar, L., Stromberg, U., Montagud, A.H., Tinnerberg, H., Forni, A., Heikkila, P., Wanders, S., Wilhardt, P., Hansteen, I.L., Knudsen, L.E., and Norppa, H. (2000). Chromosomal aberrations in lymphocytes predict human cancer independently of exposure to carcinogens. Cancer Res60, 1619—25.
10.
Butkiewicz, D., Grzybowska, E., Phillips, D.H., Hemminki, K., and Chorazy, M. (2000). Polymorphisms of the GSTP1 and GSTM1 genes and PAH-DNA adducts in human mononuclear white blood cells. Environ Mol Mutagen35, 99—105.
11.
Cheo, D.L., Meira L.B., Burns, D.K., Reis, A.M., Issac, T., and Friedberg, E.C. (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 Res60, 1580—4.
12.
Cloos, J., Nieuwenhuis, E.J.C., Boomsma, D.I., Kuik, D.J., van der Sterre, M.L.T., Arwert, F., Snow, G.B., and Braakhuis, B.J.M. (1999). Inherited susceptibility to bleomycin-induced chromatid breaks in cultured peripheral blood lymphocytes . J Natl Cancer Inst91, 1125—30.
13.
Collins, F.S., Brooks, L.D., and Chakravarti, A. (1998). A DNA polymorphism discovery resource for research on human genetic variation. Genome Res8, 1229—31.
14.
Cooper, R.S., and Psaty, B.M. (2003). Genomics and medicine: distraction, incremental progress, or the dawn of a new age. Ann Intern Med138, 576—80.
15.
Cox, N.J. (2001). Challenges in identifying genetic variation affecting susceptibility to type 2 diabetes: examples from the study of calpain-10 gene . Human Mol Genet10, 2301—5.
16.
Daly, A.K. (2003). Pharmacogenetics of the major polymorphic metabolizing enzymes. Fund Clin Pharmacol17, 27—41.
17.
Doris, P.A. (2001). Hypertension genetics, single nucleotide polymorphisms, and the common disease: common variant hypothesis. Hypertension39, 323—31.
18.
Duell, E.J., Wiencke, J.K., Cheng, T.J., Varkonyi, A., Zuo, Z.F., Ashok, T.D., Mark, E.J., Wain, J.C., Christiani, D.C., and Kelsey, K.T. (2000). Polymorphisms in the DNA repair genes XRCC1 and ERCC2 and biomarkers of DNA damage in human blood mononuclear cells. Carcinogenesis21, 965—71.
19.
Evans, W.E. (2003). Pharmacogenomics: marshalling the human genome to individualise drug therapy. Gut52, 10—18.
20.
Evans, W.E., and McLeod, H.L. (2003). Pharmacogenomics—drug disposition, drug targets, and side effects. N Engl J Med348, 538—49.
21.
Flockhart, D.A., and Rae, J.M. (2003). Cytochrome P4503A pharmacogenetics: the road that needs traveled. Pharmacogenomics J3, 3—7.
22.
Friedberg, E.C., Walker, G.C., and Siede, W. (1995). DNA Repair and Mutagenesis. ASM Press, Washington, DC.
23.
Garner, R.C. (1998). The role of DNA adducts in chemical carcinogenesis . Mutat Res402, 67—75.
24.
Goode, E.L., Ulrich, C.M., and Potter, J.D. (2002). Polymorphisms in DNA repair genes and associations with cancer risk. Cancer Epidemiol. Biomarkers Prev11, 1513—30.
Grossman, L., Matanoski, G., Farmer, E., Hedayati, M., Ray, S., Trock, B., Hanfelt, J., Roush, G., Berwick, M., and Hu, J.J. (1999). DNA repair as a susceptibility factor in chronic diseases in human populations. In Advances in DNA Damage and Repair (M. Dizdaroglu and A. E. Karakaya, eds.), pp. 149—167. Kluwer Academic/Plenum Publishers, New York.
27.
Gupta, R.C., and Lutz, W.K. (1999). Background DNA damage for endogenous and unavoidable exogenous carcinogens, a basis for spontaneous cancer incidence?Mutat Res424, 1—8.
28.
Hadi, M., Coleman, M., Fidelis, K., Mohrenweiser, H.W., and Wilson, III D.W. (2000). Functional characterization of Ape1 variants identified in the human population. Nucl Acids Res28, 3871—9.
29.
Hagmar, L., Bonassi, S., Stromberg, U., Brogger, A., Knudsen, L.E., Norppa, H., and Reuterwall, C. (1998). Chromosomal aberrations in lymphocytes predict human cancer: a report from the European Study Group on Cytogenetic Biomarkers and Health (ESCH). Cancer Res58, 4117—21.
30.
Hemminki, K., Koskinen, M., and Zhao, C. (2001). DNA adducts as a marker for cancer risk? Int J Cancer92, 923—6.
31.
Hoeijmakers, J.H. (2001). Genome maintenance mechanisms for preventing cancer . Nature411, 366—74.
32.
Hopper, J.L. (2001). Genetic epidemiology of female breast cancer. Semin Cancer Biol11, 367—74.
33.
Hsieh, P. (2001). Molecular mechanisms of DNA mismatch repair. Mutat Res486, 71—87.
34.
Hu, J.J., Smith, T.R., Miller, M.R., Mohrenweiser, H.W., Golden, A., and Case, L.D. (2001). Amino acid substitution variants of APE1 and XRCC1 genes associated with ionizing radiation sensitivity. Carcinogenesis22, 917—22.
35.
Ihle, J.N. (2000). The challenge of translating knockout phenotypes into gene function. Cell102, 131—4.
36.
Ingelman-Sundberg, M., and Evans, W.E. (2001). Unraveling the functional genomics of the human CYP2D6 gene locus. Pharmacogenetics11, 553—4.
37.
Ishikawa, T., Ide, F., Qin, X., Zhang, S., Takahashi, Y., Sekiguchi, M., Tanaka, K., and Nakatsuru, Y. (2001). Importance of DNA repair in carcinogenesis: evidence from transgenic and gene targeting studies. Mutat Res477, 41—9.
38.
Jones, I.M., Galick, H., Kato, P., Langlois, R.G., Mendelsohn, M.L., Murphy, G.A., Pleshanov, P., Ramsey, M.J., Thomas, C.B., Tucker, J.D., Tureva, L., Vorobtsova, I., and Nelson, D.O. (2002). Three somatic genetic biomarkers and covariates in radiation-exposed Russian cleanup workers of the chernobyl nuclear reactor 6-13 years after exposure. Radiat Res158, 424— 42.
39.
Jones, I.M., Nelson, D.O., Thomas, C.B., Xi, T., and Mohrenweiser, H.M. (2003). Low frequency variants contribute to base excision repair pathway genotype-phenotype relationships . Cancer Res44, 1337.
40.
Jyothish, B., Ankathil, R., Chandini, R., Vinodkumar, B., Nayar, G.S., Roy, D.D., Madhavan, J., and Nair, M.K. (1998). DNA repair proficiency: a potential marker for identification of high risk members in breast cancer families. Cancer Lett124, 9—13.
41.
Kaina, B., Fritz, G., Ochs, K., Haas, S., Grombacher, T., Dosch, J., Christmann, M., Lund, P., Gregel, C.M., and Becker, K. (1998). Transgenic systems in studies on genotoxicity of alkylating agents: critical lesions, thresholds and defense mechanisms . Mutation Res405, 179—91.
42.
Kalow, W. (2001). Pharmacogenetics, pharmacogenomics, and pharmacobiology . Clin Pharm Therap70, 1—4.
43.
Kalow, W. (2002). Pharmacogenetics and pesonalized medicine. Fund Clin Pharmacol16, 337—42.
44.
Kucherlapati, M., Yang, K., Kuraguchi, M. Zhao, J., Lia, M., Heyer, J., Kane, M. F. Fan, K., Russell, R., Brown, A. M., Kneitz, B., Edelmann, W., Kolodner, R. D., Lipkin, M., and Kucherlapti, R. (2002). Haploinsufficiency of Flap endonuclease (Fen1) leads to rapid tumor progression . Proc Natl Acad Sci USA99, 9924—9.
Lash, L.H., Hines, R.N., Gonzalez, F.J., Zacharewski, T.R., and Rothstein, M.A. (2003). Genetics and susceptibility to toxic chemicals: do you (or should you) know your genetic profile? J Pharmacol Exp Therap305, 403—40.
47.
Liang, G., Xing, D., Miao, X., Tan, W., Yu, C., Lu, W., and Lin, D. (2003). Sequence variations in the DNA repair gene XPD and risk of lung cancer in a Chinese population. Int J Cancer105, 669—73.
48.
Lindahl, T. (1993). Instability and decay of the primary structure of DNA. Nature362, 709—15.
49.
Lindpaintner, K. (2003). Pharmacogenetics and the future of medical practice . J Mol Med81, 141—53.
50.
Lutz. W.K. (1999). Dose-response relationships in chemical carcinogenesis reflect differences in individual susceptibility. Consequences for cancer risk assessment, extrapolation, and prevention. Hum Exp Toxicol18, 707— 12.
51.
Lunn, R.M., Langlois, R.G., Hsieh, L.L., Thompson, C.L., and Bell, D.A. (1999). XRCC1 polymorphisms: effects on aflatoxin B1-DNA adducts and glycophorin A variant frequency. Cancer Res59, 2557—61.
52.
Meira, L.B., Devaraj, S., Kisby, G.E., Burns, D.K., Daniel, R.L., Hammer, R.E., Grundy, S., Jialal, I., and Friedberg, E.C. (2001a). Heterozygosity for the mouse Apex gene results in phenotypes associated with oxidative stress. Cancer Res61, 5552—7.
53.
Meira, L.B., Reis, A.M., Cheo, D.L., Nahari, D., Burns, D.K., and Friedberg, E.C. (2001b). Cancer predisposition in mutant mice defective in multiple genetic pathways: uncovering important genetic interactions. Mutat Res477, 51—8.
54.
Mohrenweiser, H.W., and Jones, I.M. (1998). Variation in DNA repair is a factor in cancer susceptibility: a paradigm for the promises and perils of individual and population risk estimation?Mutat Res400, 15—24.
55.
Mohrenweiser, H.W., Wilson III, D.M., and Jones, I.M. (2003a). Challenges and complexities in estimating both the functional impact and the disease risk associated with the extensive genetic variation in human DNA repair genes. Mutat Res256, 93—125.
56.
Mohrenweiser, H.W., Xi, T., and Jones, I.M. (2003b). Many common amino acid substitutions variants identified in DNA repair genes during population based screenings are predicted to impact protein function. Cancer Res44, 1337.
57.
Mohrenweiser, H.W., Xi, T., Vazquez-Matias, J., and Jones, I.M. (2002). Identification of 127 amino acid substitution variants in screening 37 DNA repair genes in humans. Cancer Epidemiol Biomarkers Prev11, 1054— 64.
58.
Moller, P., Wallin, H., Dybdahl, M., Frentz, G., and Nexo, B.A. (2000). Psoriasis patients with basal cell carcinoma have more repair-mediated DNA strand-breaks after UVC damage in lymphocytes than psoriasis patients without basal cell carcinoma. Cancer Lett151, 187—92.
59.
Ng, P.C., and Henikoff, S. (2001). Predicting deleterious amino acid substitutions . Genome Res11, 863—74.
60.
Ng, P.C., and Henikoff, S. (2002). Accounting for human polymorphisms predicted to affect protein function. Genome Res12, 436—46.
61.
Nwosu, V., Carpten, J., Trent, J.M., and Sheridan, R. (2001). Heterogeneity of genetic alterations in prostate cancer: evidence of the complex nature of the disease. Hum Mol Genet10, 2313—8.
62.
Oscarson, M. (2003). Pharmacogenetics of drug metabolizing enzymes: importance for personalized medicine. Clin Chem Lab Med41, 573—80.
63.
Orphanides, G. (2002). Toxicogenomics: challenges and opportunities. Toxicol Lett140—141, 145—8.
64.
Patel, R.K., Trivedi, A.H., Arora, D.C., Bhatavdekar, J.M., and Patel, D.D. (1997). DNA repair proficiency in breast cancer patients and their firstdegree relatives. Int J Cancer73, 20—4.
65.
Peterson, G.M. (2000). Familial aggregation: sorting susceptibility from shared environment. J Natl Cancer Inst92, 1114—5.
66.
Peto, J., Easton, D.F., Matthews, F.E., Ford, D., and Swerdlow, A.J. (1996). Cancer mortality in relatives of women with breast cancer: the OPCS study. Int J Cancer65, 275—83.
67.
Perera, F.P. (2000). Molecular epidemiology: on the path to prevention ? J Natl Cancer Inst92, 602—12.
68.
Phillips, D.H., Farmer, P.B., Beland, F.A., Nath, R.G., Poirier, M.C., Reddy, M.V., and Turteltaub, K.W. (2000). Methods of DNA adduct determination and their application to testing compounds for genotoxicity. Environ Mol Mutagen35, 222—33.
69.
Ponder, B.A.J. (2001). Cancer genetics. Nature411, 336—41.
70.
Povey, A.C. (2000). DNA adducts: endogenous and induced. Toxicol Pathol28, 405—14.
71.
Povirk, L.F. (1996). DNA damage and mutagenesis by radiomimetic DNA-cleaving agents: bleomycin, neocarzinostatin and other enediynes. Mutat Res355, 71—89.
72.
Qiao, Y., Spitz, M.R., Guo, Z., Hadeyati, M., Grossman, L., Kraemer, K.H., and Wei, Q. (2002a). Rapid assessment of repair of ultraviolet DNA damage with a modified host-cell reactivation assay using a luciferase reporter gene and correlation with polymorphisms of DNA repair genes in normal human lymphocytes. Mutat Res509, 165—74.
73.
Qiao, Y., Spitz, M.R., Shen, H., Guo, Z., Shete, S., Hedayati, M., Grossman, L., Mohrenweiser, H., and Wei, Q. (2002b). Modulation of repair of ultraviolet damage in the host-cell reactivation assay by polymorphic XPC and XPD/ERCC2 genotypes . Carcinogenesis23, 295—99.
74.
Ramensky, V., Bork, P., and Sunyaev, S. (2002). Human non-synonymous SNPs: server and survey. Nucl Acids Res30, 3894—900.
75.
Ratnasinghe, D.L., Yao, S.X., Forman, M., Qiao, Y.L., Andersen, M.R., Giffen, C.A., Erozan, Y., Tockman, M.S., and Taylor, P.R. (2003). Gene-environment interactions between the codon 194 polymorphism of XRCC1 and antioxidants influence lung cancer risk. Anticancer Res23, 627—32.
76.
Risch, N.J. (2000). Searching for genetic determinants in the new millennium. Nature405, 847—56.
77.
Risch, N.J. (2001). The genetic epidemiology of cancer: interpreting family and twin studies and their implications for molecular genetic approaches . Cancer Epidemiol Biomarkers Prev10, 733—41.
78.
Roberts, S.A., Spreadborough. A.R., Bulman, B., Barber, J.B.P., Evans, D.G.R., and Scott, D. (1999). Heritability of cellular radiosensitivity: a marker of low-penetrance predisposition genes in breast cancer. Am J Hum Genet65, 784—94.
79.
Rogers, J.F., Nafziger, A.N., and Bertino, J.S. (2002). Pharmacogenetics affects dosing, efficacy, and toxicity of Cytochrome P450-Metabolized drugs. Excerpta Medica113, 746—50.
80.
Rothman, N., Wacholder, S., Caporaso, N.E., Garcia-Closas, M., Buetow, K., and Fraumeni, Jr. J.F. (2001) The use of common genetic polymorphisms to enhance the epidemiologic study of environmental carcinogens . Biochim Biophys Acta1471, C1—C10.
81.
Sachidanandam, R., Weissman, D., Schmidt, S.C., Kakol, J.M., Stein, L.D., et al. (2001). A map of human genome sequence variation containing 1.42 million single nucleotide polymorphisms. Nature409, 928—33.
82.
Savas, S., Knight, J.A., Briollais, L., and Ozcelik, H. (2002). Prediction of deleterious single nucleotide polymorphisms (SNPs) in DNA repair genes for breast cancer association studies. Cancer Epidemiol Biomarkers Prev11, 1178s.
83.
Sellers, T.A., Potter, J.D., Bailey-Wilson, J.E., Rich, S.S., Rothschild, H., and Elston, E.R. (1992). Lung cancer detection and prevention: Evidence for interaction between smoking and genetic predisposition. Cancer Res52, 2694—7.
84.
Shen, M.J., Jones, I., and Mohrenweiser, H.W. (1998). Non-conservative amino acid substitutions exist at polymorphic frequency in DNA repair genes. Cancer Res58, 604—8.
85.
Shi, M.M., Bleavins, M.R., and de La Iglesia, F.A. (2001). Pharmacogenetic application in drug development and clinical trials. Drug Metab. Disposit29, 591—5.
86.
Shields, P.G., and Harris, C.C. (2000). Cancer risk and low-penetrance susceptibility genes in gene environment interactions. J Clin Oncol182309—15.
87.
Siest, G., Ferrari, F., Accaoui, M.J., Batt, A.M., and Visvikis, S. (2003). Pharmacogenomics of drugs affecting the cardiovascular system. Clin Chem Lab Med41, 590—9.
88.
Smith, T.R., Miller, M.S., Lohman, K., Lange, E.M., Case, L.D., Mohrenweiser, H.W., and Hu J.J. (2003). Polymorphisms of XRCC1 and XRCC3 genes and susceptibility to breast cancer. Cancer Lett190, 183—90.
89.
Spring, K., Ahangari, F., Scott, S.P., Waring, P., Purdie, D.M., Chen, P.C., Hourigan, K., Ramsay, J., McKinnon, P.J., Swift, M., and Lavin, M.F. (2002). Mice heterozygous for mutation in Atm, the gene involved in ataxia- telangiectasia, have heightened susceptibility to cancer . Nature Genet32, 185—90.
90.
Steinke, J.W., Borish, L., and Rosenwasser, L.J. (2003). Genetics of hypersensitivity . J Allergy Clin Immunol111, 495—501.
91.
Sunyaev, S., Ramensky, V., Koch, I., Lathe, W., Kondrashov, A.S., and Bork, P. (2001). Prediction of deleterious human alleles. Hum Mol Genet10, 591—7.
92.
Thomas, C.B., Nelson, D.O., Pleshanov, P., Vorobstova, I., Tureva, L., Jensen, R., and Jones I.M. (1999). Elevated frequencies of hypoxanthine phosphoribosyltransferase lymphocyte mutants are detected in Russian liquidators 6 to 10 years after exposure to radiation from the Chernobyl nuclear power plant accident. Mutat Res439, 105—19.
93.
Thompson, L.H., and Schild, D. (2001). Homologous recombinational repair of DNA ensures mammalian chromosome stability. Mutat Res477, 131—53.
94.
Turner, S.T., and Boerwinkle, E. (2003). Genetics of blood pressure, hypertensive complications, and antihypertensive drug responses. Pharmacogenomics4, 53—65.
95.
Vineis, P. (1997). Molecular epidemiology: low-dose carcinogens and genetic susceptibility. Int J Cancer71, 1—3.
96.
Vineis, P., and Perera, F. (2000). DNA adducts as markers of exposure to carcinogens and risk of cancer. Int J Cancer88, 325—8.
97.
Vogel, V., Hedayati, M., Dybdahl, M., Grossman, L., and Nexo, B.A. (2001). Polymorphisms of the DNA repair gene XPD: correlations with risk of basal cell carcinoma revisited. Carcinogenesis22, 899—904.
98.
Wang, Z., and Moult, J. (2001). SNPs, protein structure, and disease. Hum Mutat17, 263—70.
99.
Weinshilboum, R. (2001). Thiopurine pharmacogenetics: clinical and molecular studies of thiopurine methyltransferase. Drug Metab Disposit29, 601—5.
100.
Weinshilbourn, R. (2003). Inheritance and drug response. N Engl J Med348, 529—37.
101.
Welsch, P.L., Owens, K.N., and King, M.C. (2000). Insights into the functions of BRCA1 and BRCA2 . Current Opin Genet Develop7, 46—51.
102.
Whyatt, R.M., Perera, F.P., Jedrychowski, W., Santella, R.M., Garte, S., and Bell, D.A. (2000). Association between polycyclic aromatic hydrocarbon-DNA adduct levels in maternal and newborn white blood cells and glutathione S-transferase P1 and CYP1A1 polymorphisms. Cancer Epidemiol Biomarkers Prev9, 207—12.
103.
Wolf, C.R., Smith, G., and Smith, R.L. (2000). Pharmacogenetics. Brit Med J320, 987—90.
104.
Wood, R.D., Mitchell, M., Sgouros, J., and Lindahl, T. (2001). Human DNA repair genes. Science291, 1284—9.
105.
Worgul, B.V., Smilenov, L., Brenner, D.J., Junk, A., Zhou, W., and Hall, E.J. (2002). Atm heterozygous mice are more sensitive to radiation-induced cataracts than are their wild-type counterparts. Proc Natl Acad Sci USA99, 9836—9.
106.
Wu, X., Gu, J., Amos, C.I., Jiang, H., Hong, W.K., and Spitz, M.R. (1998a). A parallel study of in vitro sensitivity to benzo[a]pyrene diol epoxide and bleomycin in lung carcinoma cases and control. Cancer83, 1118—27.
107.
Wu, X., Gu, J., Hong, W.K., Lee, J.J., Amos, C.I., Jiang, H., Winn, R.J., Fu, K.K., Cooper, J., and Spitz, R. (1998b). Benzo[a]pyrene diol epoxide and bleomycin sensitivity and susceptibility to cancer of upper aerodigestive tract. J Natl Cancer Inst90, 1393—9.
108.
Wu, X., Spitz, M.R., DeAndrade, M., Benowitz, N.L., and Swan, G.E. (2000). Genetic influence on mutagen sensitivity: a twin study. Proc Amer Assoc Cancer Res41, 437.
109.
Wu, X., Zhao, H., Wei, Q., Amos, C.I., Zhang, K., Guo, Z., Qiao, Y., Hong, W.K., and Spitz, M.R. (2003). XPA polymorphism associated with reduced lung cancer risk and a modulating effect on nucleotide excision repair capacity . Carcinogenesis24, 505—9.
110.
Xu, J., Meyers, D.A., Ober, C., Blumenthal, M.N., Mellen, B., et. al. (2001). Genomewide screen and identification of gene-gene interactions for asthma-susceptibility loci in three U.S. populations: collaborative study of the genetics of asthma. Am J Human Genet68, 1437—46.
111.
Zanger, U.M., Fischer, J., Raimundo, S., Stuven, T., Evert, B.O., Schwab, M., and Eichelbaum, M. (2001). Comprehensive analysis of the genetic factors determining expression and function of hepatic CYP2D6. Pharmacogenetics11, 573—85.
112.
Zhang, Z.F., Morgenstern, H., Spitz, M.R., Tashkin, D.P., Yu, G.P., Hsu, T.C., and Schantz, S.P. (2000). Environmental tobacco smoking, mutagen sensitivity, and head and neck squamous cell carcinoma. Cancer Epidemiol Biomarkers Prev9, 1043—9.
113.
Zhou, W., Liu, G., Miller, D.P., Thurston, S.W., Xu, L.L., Wain, J.C., Lynch, T.J., Su, L., and Christiani, D.C. (2003). Polymorphisms in the DNA repair genes XRCC1 and ERCC2, smoking, and lung cancer risk. Cancer Epidemiol Biomarkers Prev12, 359—65.
