Molecular genetics of cancer susceptibility

被引:48
作者
Brockmöller, J [1 ]
Cascorbi, I [1 ]
Henning, S [1 ]
Meisel, C [1 ]
Roots, I [1 ]
机构
[1] Free Univ Berlin, Klinikum Charite, Inst Klin Pharmakol, D-10098 Berlin, Germany
关键词
cancer; molecular epidemiology; cytochrome P450; glutathione S-transferase; arylamine N-acetyltransferase; myeloperoxidase; DNA repair; pharmacogenetics; pharmacogenomics; MDR1; polymorphism;
D O I
10.1159/000028403
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
Studies on the role of genetically polymorphic enzymes like cytochrome P450 1A1, arylamine N-acetyltransferase 2 or glutathione S-transferase M1 as cancer susceptibility factors date back more than 20 years, and some associations have been confirmed in several studies and meta-analyses. Overall, the extent of risk modulation due to these polymorphisms is only moderate but remains epidemiologically relevant. The role of some of these polymorphisms in human health may even be ambiguous: rapid acetylation, for example, protects from urinary bladder cancer but appears to increase the risk of laryngeal, lung and colon cancer. The first genetic polymorphisms in xenobiotics transporters such as P-gp (MDR1) and MRP2 have recently been identified. These polymorphisms may have great impact as cancer susceptibility factors as well as factors modulating the out-come of cancer treatment. Enzymes involved in generation or detoxification of reactive oxygen species also have to be considered; one of these enzymes, myeloperoxidase, constitutes a relatively strong lung cancer risk factor, as confirmed in 4 independent studies. Other genes, including those coding for DNA repair enzymes, signal transduction and cell growth regulation, may ultimately prove more important than the metabolic enzymes as cancer susceptibility factors. Study designs in molecular genetic epidemiology are evolving; large ongoing prospective trials increasingly allow confirmatory nested case control studies to be performed. However, carefully controlled, large case-control studies will remain the mainstay in molecular genetic epidemiology. Molecular genetic epidemiological evaluation of response to chemoprevention as well as response to the adverse events of cancer chemotherapy are likely to provide results that may be useful for individualized prevention and treatment in the near future. Since routine genotyping of all persons is now feasible, something like a genotype passport may soon become reality, and molecular and clinical epidemiological studies will have to provide the basis for understanding how to use genotype data for the benefit of the population. Copyright(C) 2000 S. KargerAG. Basel.
引用
收藏
页码:212 / 227
页数:16
相关论文
共 73 条
  • [21] Mutation analysis of 8p genes POLB and PPP2CB in bladder cancer
    Eydmann, ME
    Knowles, MA
    [J]. CANCER GENETICS AND CYTOGENETICS, 1997, 93 (02) : 167 - 171
  • [22] Polymorphisms in the human DNA repair gene XPF
    Fan, F
    Liu, CP
    Tavaré, S
    Arnheim, N
    [J]. MUTATION RESEARCH-GENOMICS, 1999, 406 (2-4): : 115 - 120
  • [23] Gamcsik MP, 1999, CURR PHARM DESIGN, V5, P587
  • [24] Frequency of glutathione S-transferase M1 deletion in smokers with emphysema and lung cancer
    Harrison, DJ
    Cantlay, AM
    Rae, F
    Lamb, D
    Smith, CAD
    [J]. HUMAN & EXPERIMENTAL TOXICOLOGY, 1997, 16 (07): : 356 - 360
  • [25] Association between glutathione S-transferase M1, P1, and T1 genetic polymorphisms and development of breast cancer
    Helzlsouer, KJ
    Selmin, O
    Huang, HY
    Strickland, PT
    Hoffman, S
    Alberg, AJ
    Watson, M
    Comstock, GW
    Bell, D
    [J]. JOURNAL OF THE NATIONAL CANCER INSTITUTE, 1998, 90 (07) : 512 - 518
  • [26] ENVIRONMENT AND DISEASE - ASSOCIATION OR CAUSATION
    HILL, AB
    [J]. PROCEEDINGS OF THE ROYAL SOCIETY OF MEDICINE-LONDON, 1965, 58 (05): : 295 - +
  • [27] Functional polymorphisms of the human multidrug-resistance gene:: Multiple sequence variations and correlation of one allele with P-glycoprotein expression and activity in vivo
    Hoffmeyer, S
    Burk, O
    von Richter, O
    Arnold, HP
    Brockmöller, J
    Johne, A
    Cascorbi, I
    Gerloff, T
    Roots, I
    Eichelbaum, M
    Brinkmann, U
    [J]. PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2000, 97 (07) : 3473 - 3478
  • [28] CYP1A1 polymorphisms and lung cancer risk:: a meta-analysis
    Houlston, RS
    [J]. PHARMACOGENETICS, 2000, 10 (02): : 105 - 114
  • [29] THE PHARMACOGENETICS OF CHEMICAL CARCINOGENESIS
    IDLE, JR
    ARMSTRONG, M
    BODDY, AV
    BOUSTEAD, C
    CHOLERTON, S
    COOPER, J
    DALY, AK
    ELLIS, J
    GREGORY, W
    HADIDI, H
    HOFER, C
    HOLT, J
    LEATHART, J
    MCCRACKEN, N
    MONKMAN, SC
    PAINTER, JE
    TABER, H
    WALKER, D
    YULE, M
    [J]. PHARMACOGENETICS, 1992, 2 (06): : 246 - 258
  • [30] IMAI Y, 1995, CARCINOGENESIS, V16, P2441