title: Molecular epidemiology of human cancer risk: gene-environment interactions and p53 mutation spectrum in human lung cancer.
abstract: The p53 tumour suppressor gene is at the crossroads of a network of cellular pathways including cell cycle checkpoints, DNA repair, chromosomal segregation, and apoptosis. These pathways have evolved to maintain the stability of the genome during cellular stress from DNA damage, hypoxia, and activated oncogenes. The high frequency of p53 mutations in human cancer is a reflection of the importance of p53 involvement in this network of pathways during human carcinogenesis. An electronic database containing p53 mutations from more than 9000 cancers (http:/(/)www.iarc.fr/p53/homepage.html) can be used to generate hypotheses for further clinical, epidemiological, and laboratory investigations. For example, one can hypothesize that (a) p53 mutations vary in their pathobiological significance; (b) cellular content influences the selection of p53 mutations in clonally derived cancers; (c) the location and type of mutation within the p53 gene provide clues to functional domains in the gene product; and (d) the p53 mutation spectrum can be a molecular link between aetiological agents and human cancer. This review will focus on the role of p53 and cancer susceptibility genes in the molecular pathogenesis and epidemiology of human lung cancer.
authors.affiliation: Division of Human Genetics, City of Hope, National Medical Center, Duarte, CA, USA.
authors.forename: W P
authors.initials: WP
authors.lastname: Bennett
authors.forename: S P
authors.initials: SP
authors.lastname: Hussain
authors.forename: K H
authors.initials: KH
authors.lastname: Vahakangas
authors.forename: M A
authors.initials: MA
authors.lastname: Khan
authors.forename: P G
authors.initials: PG
authors.lastname: Shields
authors.forename: C C
authors.initials: CC
authors.lastname: Harris
mesh_terms: D003043:Cocarcinogenesis; D004777:Environment; D016158:Genes, p53; D006801:Humans; D008175:Lung Neoplasms / Q000453:epidemiology* / Q000235:genetics*; D009154:Mutation; D012907:Smoking / Q000235:genetics