The relationship between polymorphisms of xenobiotic metabolizing enzymes and susceptibility to cancer. 2002

Paolo Vineis
Dipartimento di Scienze Biomediche e Oncologia Umana, Unit of Cancer Epidemiology, University of Torino and ISI Foundation, via Santena 7, 10126 Torino, Italy. paolo.vineis@unito.it

Although it is well established that highly penetrant genes explain less than 5% of all cancers, it is much less clear what proportion is attributable to low penetrant genes and their interactions with environmental exposures. It was possible to estimate indirectly the fraction of lung and bladder cancers attributable to known genetic polymorphisms, on the basis of an extensive review of the literature, and of the pooled analyses of approximately 15000 healthy subjects in three continents. The emerging picture is one of considerable homogeneity within ethnic group, and heterogeneity among ethnic groups. By combining relative risks and genotype frequencies we have computed theoretical attributable risks for lung and bladder cancers and the CYP1A1 Msp1, CYP1A1 Exon 7, GSTM1 and NAT2*5 genotypes, among Caucasians and among Asians. Such attributable risks are probably overestimated, since: (a) they include the interaction with carcinogenic exposures, in the absence of which genetic polymorphisms per se are not effective; (b) they do not reflect the combination of different genotypes. However, our calculations suggest that attributable risks due to genetic susceptibility are much lower than those related to smoking or other environmental risk factors, and that Asians seem to carry higher risks than Caucasians. In addition, a theoretical approach to the problem of gene-environment interactions at low levels of exposure is offered.

UI MeSH Term Description Entries
D008954 Models, Biological Theoretical representations that simulate the behavior or activity of biological processes or diseases. For disease models in living animals, DISEASE MODELS, ANIMAL is available. Biological models include the use of mathematical equations, computers, and other electronic equipment. Biological Model,Biological Models,Model, Biological,Models, Biologic,Biologic Model,Biologic Models,Model, Biologic
D009369 Neoplasms New abnormal growth of tissue. Malignant neoplasms show a greater degree of anaplasia and have the properties of invasion and metastasis, compared to benign neoplasms. Benign Neoplasm,Cancer,Malignant Neoplasm,Tumor,Tumors,Benign Neoplasms,Malignancy,Malignant Neoplasms,Neoplasia,Neoplasm,Neoplasms, Benign,Cancers,Malignancies,Neoplasias,Neoplasm, Benign,Neoplasm, Malignant,Neoplasms, Malignant
D011110 Polymorphism, Genetic The regular and simultaneous occurrence in a single interbreeding population of two or more discontinuous genotypes. The concept includes differences in genotypes ranging in size from a single nucleotide site (POLYMORPHISM, SINGLE NUCLEOTIDE) to large nucleotide sequences visible at a chromosomal level. Gene Polymorphism,Genetic Polymorphism,Polymorphism (Genetics),Genetic Polymorphisms,Gene Polymorphisms,Polymorphism, Gene,Polymorphisms (Genetics),Polymorphisms, Gene,Polymorphisms, Genetic
D002273 Carcinogens Substances that increase the risk of NEOPLASMS in humans or animals. Both genotoxic chemicals, which affect DNA directly, and nongenotoxic chemicals, which induce neoplasms by other mechanism, are included. Carcinogen,Oncogen,Oncogens,Tumor Initiator,Tumor Initiators,Tumor Promoter,Tumor Promoters,Initiator, Tumor,Initiators, Tumor,Promoter, Tumor,Promoters, Tumor
D004777 Environment The external elements and conditions which surround, influence, and affect the life and development of an organism or population. Environmental Impact,Environmental Impacts,Impact, Environmental,Impacts, Environmental,Environments
D006801 Humans Members of the species Homo sapiens. Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D015262 Xenobiotics Chemical substances that are foreign to the biological system. They include naturally occurring compounds, drugs, environmental agents, carcinogens, insecticides, etc. Xenobiotic
D019683 Penetrance The percent frequency with which a dominant or homozygous recessive gene or gene combination manifests itself in the phenotype of the carriers. (From Glossary of Genetics, 5th ed)

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