Molecular epidemiology of human cancer risk: Gene-environment interactionsand p53 mutation spectrum in human lung cancer

Citation
Wp. Bennett et al., Molecular epidemiology of human cancer risk: Gene-environment interactionsand p53 mutation spectrum in human lung cancer, J PATHOLOGY, 187(1), 1999, pp. 8-18
Citations number
126
Categorie Soggetti
Research/Laboratory Medicine & Medical Tecnology","Medical Research Diagnosis & Treatment
Journal title
JOURNAL OF PATHOLOGY
ISSN journal
00223417 → ACNP
Volume
187
Issue
1
Year of publication
1999
Pages
8 - 18
Database
ISI
SICI code
0022-3417(199901)187:1<8:MEOHCR>2.0.ZU;2-X
Abstract
The p53 tumour suppressor gene is at the crossroads of a network of cellula r pathways including cell cycle checkpoints, DNA repair, chromosomal segreg ation, and apoptosis, These pathways hare evolved to maintain the stability of the genome during cellular stress from DNA damage, hypoxia, and activat ed oncogenes, The high frequency of p53 mutations in human cancer is a refl ection of the importance of p53 involvement in this network of pathways dur ing human carcinogenesis. An electronic database containing p53 mutations f rom more than 9000 cancers (http://www.iarc.fr/p53/homepage.html) can be us ed to generate hypotheses for further clinical, epidemiological, and labora tory investigations. For example, one can hypothesize that (a) p53 mutation s vary in their pathobiological significance; (b) cellular content influenc es the selection of p53 mutations in clonally derived cancers; (c) the loca tion and type of mutation within the p53 gene provide clues to functional d omains in the gene product; and (d) the p53 mutation spectrum can be a mole cular link between aetiological agents and human cancer. This review will f ocus on the role of p53 and cancer susceptibility genes in the molecular pa thogenesis and epidemiology of human lung cancer. Copyright (C) 1999 John W iley & Sons, Ltd.