Interaction of environmental factors and genetic polymorphism in the etiology of cancer

Еnvironmental and lifestyle factors play a dominant role in etiology of cancer. In addition, genetic factors significantly influence interindividual variation in cancer incidence. The epidemiological studies in which effects of genetic polymorphism on the risk of cancer have been elucidated are somewhat disappointing. An important problem of these studies is their size. Moreover some of them do not have information on life-style and environmental exposures. The epidemiological method used to investigate the effect of genetic polymorphism on cancer risk is a retrospective case-control study. The chance of discovery of the specific «frequent» allelic variant which is associated with small increase in the risk is higher in studies including large numbers of cases and controls. This paper reviews the epidemiologic studies conducted in Department of epidemiology (Institute of carcinogenesis, Russian N. N. Blokhin Cancer Research Centre) in cooperation with countries of Central and Eastern Europe (Hungary, Poland, Romania, Slovakia) and coordinated by the International Agency for Research on Cancer (IARC). We will cover the studies, in which an attempt has been made to investigate the interaction between polymorphisms of phase 2 xenobiotic metabolism genes (GST), alcohol and aldehyde-metabolizing genes (ADH, ALDH), folate metabolism genes (MTHFR, TYMS) and CHECK2 with environmental and life-style factors in etiology of cancers of the lung, kidney and upper aerodigestive tract. The analyses of these studies suggest that genetic polymorphism modifies the effect of environmental exposures (including occupational carcinogens) and life-style factors (including tobacco, alcohol and diet) on the risk of cancer. The risk of cancer associated with known carcinogenic exposure may increase or decrease depending on the genotype. Interaction between exposure to carcinogenic factor and genotype is a major and significant determinant of cancer risk. Spontaneous tumors develop as a result of a combined effect of environmental factors and genetic polymorphism or endogenous and exogenous factors.

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