Drug metabolism polymorphisms as modulators of cancer susceptibility

Taningher, Maurizio; Malacarne, Davide; Izzotti, Alberto; Ugolini, Donatella; Parodi, Silvio

doi:10.1016/s1383-5742(99)00005-8

Cited by 137 publications

(71 citation statements)

References 119 publications

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“…Indeed, inherited genes that encode enzymes involved in the activation or detoxification of exogenous carcinogenic factors are much more frequent. These genes are polymorphic in nature, meaning that they are a common variant of the enzyme genes (39,113). As a consequence of polymorphism, individual variations in the metabolism of carcinogens account for differences in susceptibility to cancer and could thus impact on the population attributable risk for cancer.…”

Section: Genetic Versus Environmental Influencesmentioning

confidence: 99%

The growing incidence of cancer: Role of lifestyle and screening detection (Review)

Belpomme¹,

Irigaray²,

Sasco³

et al. 2007

Int J Oncol

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Abstract. The increasing incidence of a variety of cancers after the Second World War confronts scientists with the question of their origin. In Western countries, expansion and ageing of the population, as well as progress in cancer detection using new diagnostic and screening tests cannot fully account for the observed growing incidence of cancer. Our hypothesis is that environmental factors play a more important role in cancer genesis than it is usually agreed: i) over the last 2-3 decades, alcohol consumption and tobacco smoking in men have significantly decreased; ii) obesity is increasing in many countries, but the growing incidence of cancer also concerns cancers not related to obesity nor to other lifestyle-related factors; iii) there is evidence that the environment has changed over the same time scale as the recent rise in cancer incidence, and that this change included the accumulation of many new carcinogenic factors in the environment; iv) genetic susceptibility to cancer due to genetic polymorphism cannot have changed over one generation and actually favours the role of exogenous factors through geneenvironment interactions; v) age is not the unique factor to be considered since the rising incidence of cancers is seen across all age categories, including children; vi) the fetus is specifically vulnerable to exogenous factors. A fetal exposure during a critical window period may explain why current epidemiological studies may be negative in adults. We therefore propose that the involuntary exposure to many carcinogens in the environment contributes to the rising trend in cancer incidence.

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Section: Genetic Versus Environmental Influencesmentioning

confidence: 99%

The growing incidence of cancer: Role of lifestyle and screening detection (Review)

Belpomme¹,

Irigaray²,

Sasco³

et al. 2007

Int J Oncol

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“…A group of enzymes, as glutathione S-transferase (GST) and N-acetil-transferase (NAT), lead this phase of metabolization process. 31 Glutathione S-transferase (GST) family includes no fewer than four classes of genes: GSTalpha, mu (GSTM), pi (GSTP), and theta (GSTT), the alleles of which have been frequently associated with some types of tumors. 1 Studies of GST genes polymorphisms and lung cancer have found associations lower than three, 9 ranging from OR 0.8 24 to OR 2.7.…”

Section: Genetic Polymorphisms and Cancermentioning

confidence: 99%

Modern cancer epidemiological research: genetic polymorphisms and environment

Filho

Zago

2005

Rev. Saúde Pública

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Individual cancer susceptibility seems to be related to factors such as changes in oncogenes and tumor suppressor genes expression, and differences in the action of metabolic enzymes and DNA repair regulated by specific genes. Epidemiological studies on genetic polymorphisms of human xenobiotics metabolizing enzymes and cancer have revealed low relative risks. Research considering genetic polymorphisms prevalence jointly with environmental exposures could be relevant for a better understanding of cancer etiology and the mechanisms of carcinogenesis and also for new insights on cancer prognosis. This study reviews the approaches of molecular epidemiology in cancer research, stressing case-control and cohort designs involving genetic polymorphisms, and factors that could introduce bias and confounding in these studies. Similarly to classical epidemiological research, genetic polymorphisms requires considering aspects of precision and accuracy in the study design. Resumo A suscetibilidade individual ao câncer envolve fatores como mudanças na expressão dos oncogenes e genes supressores de tumores e, também, diferenças em genes específicos que regulam a ação de enzimas metabólicas e de reparo do DNA. Estudos epidemiológicos relacionando polimorfismos genéticos e câncer têm mostrado riscos relativos tênues. Pesquisas abordando simultaneamente a prevalência de polimorfismos genéticos e a exposição a fatores ambientais podem conduzir a resultados relevantes para a compreensão da etiologia do câncer e dos

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“…The environment-gene interaction for cancer development is largely attributed to the action of xenobiotic metabolizing enzymes (XME). Individual differences in the bioactivation of procarcinogens and in detoxification of carcinogens, arising from alterations in XME genes, may explain varying susceptibilities to lung cancer (3,4).…”

Section: Introductionmentioning

confidence: 99%

Genetic polymorphisms of CYP1A1, GSTM1 and GSTT1 genes and lung cancer risk

Dialyna

Miyakis²,

Georgatou³

et al. 2003

Oncol Rep

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Genetic polymorphisms of the genes encoding for the xenobiotic metabolizing enzymes result in individual variations in the efficiency of detoxification of environmental carcinogens, and have been extensively associated with variable risk for lung neoplasms in different ethnic and environmental backgrounds. In this study, using PCR-RFLP based assays, we investigated the distribution of genetic polymorphisms in CYP1A1, GSTM1 and GSTT1 genes in Greek lung cancer patients (N=122) and healthy controls (N=178). The frequency of CYP1A1 m1 homozygous genotype was 0.04 in patients and 0.02 in controls (detected in 4.10% of patients and in 1.69% of controls, respectively), that of GSTM1 null genotype was 0.52 in patients and 0.54 in controls, whereas those of GSTT1 null genotype was 0.17 and 0.11, in patients and controls, respectively. The GSTM1 null genotype was more frequent in adenocarcinoma, as well as in lung cancer patients with history of chronic obstructive pulmonary disease (COPD). The GSTT1 null genotype correlated with advanced age of the patients at the time of diagnosis. Three combinations of rare genotypes -in subjects carrying simultaneously deviations from the common genotype in more than one gene -were overrepresented in lung cancer patients, compared to control population, and were furthermore significantly associated with history of heavy tobacco consumption in lung cancer patients. The results imply involvement of specific genotype combinations of CYP1A1, GSTM1 and GSTT1 alleles in the development of lung cancer in heavy smokers. Abstract. Genetic polymorphisms of the genes encoding for the xenobiotic metabolizing enzymes result in individual variations in the efficiency of detoxification of environmental carcinogens, and have been extensively associated with variable risk for lung neoplasms in different ethnic and environmental backgrounds. In this study, using PCR-RFLP based assays, we investigated the distribution of genetic polymorphisms in CYP1A1, GSTM1 and GSTT1 genes in Greek lung cancer patients (N=122) and healthy controls (N=178). The frequency of CYP1A1 m1 homozygous genotype was 0.04 in patients and 0.02 in controls (detected in 4.10% of patients and in 1.69% of controls, respectively), that of GSTM1 null genotype was 0.52 in patients and 0.54 in controls, whereas those of GSTT1 null genotype was 0.17 and 0.11, in patients and controls, respectively. The GSTM1 null genotype was more frequent in adenocarcinoma, as well as in lung cancer patients with history of chronic obstructive pulmonary disease (COPD). The GSTT1 null genotype correlated with advanced age of the patients at the time of diagnosis. Three combinations of rare genotypes -in subjects carrying simultaneously deviations from the common genotype in more than one gene -were over-represented in lung cancer patients, compared to control population, and were furthermore significantly associated with history of heavy tobacco consumption in lung cancer patients. The results imply involvement of specific genotype combinations o...

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Drug metabolism polymorphisms as modulators of cancer susceptibility

Cited by 137 publications

References 119 publications

The growing incidence of cancer: Role of lifestyle and screening detection (Review)

The growing incidence of cancer: Role of lifestyle and screening detection (Review)

Modern cancer epidemiological research: genetic polymorphisms and environment

Genetic polymorphisms of CYP1A1, GSTM1 and GSTT1 genes and lung cancer risk

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