Interaction between CYP1A2-T2467DELT polymorphism and smoking in adenocarcinoma and squamous cell carcinoma of the lung

Pavanello, Sofia; B’chir, Fatma; Pulliero, Alessandra; Saguem, Saâd; Fraj, Radhia Ben; Hayouni, Abed El Aziz; Clonfero, Erminio; Mastrangelo, Giuseppe

doi:10.1016/j.lungcan.2007.04.004

Cited by 24 publications

(19 citation statements)

References 33 publications

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“…They are in agreement with other published data (77). Some reports suggest that the CYP1A2*1F polymorphism has an important role in lung carcinogenesis, especially in squamous cell carcinoma among smokers (78). Ninety-fi ve percent of caffeine is metabolised by cytochrome CYP1A2, and caffeine induce the enzyme.…”

Section: Cyp1a2supporting

confidence: 92%

Genetic Polymorphism of Metabolic Enzymes P450 (CYP) as a Susceptibility Factor for Drug Response, Toxicity, and Cancer Risk

Božina¹,

Bradamante

Lovrić

2009

Archives of Industrial Hygiene and Toxicology

167

111

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The polymorphic P450 (CYP) enzyme superfamily is the most important system involved in the biotransformation of many endogenous and exogenous substances including drugs, toxins, and carcinogens. Genotyping for CYP polymorphisms provides important genetic information that help to understand the effects of xenobiotics on human body. For drug metabolism, the most important polymorphisms are those of the genes coding for CYP2C9, CYP2C19, CYP2D6, and CYP3A4/5, which can result in therapeutic failure or severe adverse reactions. Genes coding for CYP1A1, CYP1A2, CYP1B1, and CYP2E1 are among the most responsible for the biotransformation of chemicals, especially for the metabolic activation of pre-carcinogens. There is evidence of association between gene polymorphism and cancer susceptibility. Pathways of carcinogen metabolism are complex, and are mediated by activities of multiple genes, while single genes have a limited impact on cancer risk. Multigenic approach in addition to environmental determinants in large sample studies is crucial for a reliable evaluation of any moderate gene effect. This article brings a review of current knowledge on the relations between the polymorphisms of some CYPs and drug activity/toxicity and cancer risk.

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Section: Cyp1a2supporting

confidence: 92%

Genetic Polymorphism of Metabolic Enzymes P450 (CYP) as a Susceptibility Factor for Drug Response, Toxicity, and Cancer Risk

Božina¹,

Bradamante

Lovrić

2009

Archives of Industrial Hygiene and Toxicology

167

111

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“…The same polymorphisms were found to play a major role in rising urinary mutagenicity of smokers [8]. Moreover, CYP1A2 -2467T/delT polymorphism was found to be a significant risk modifier of smoking-induced lung cancer [9]. CYP1A2 activity may therefore be a modulating factor along the continuum from the exposure to relevant environmental and occupational exposures and certain cancers.…”

Section: Introductionmentioning

confidence: 95%

CYP1A2 polymorphisms, occupational and environmental exposures and risk of bladder cancer

et al. 2010

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Cytochrome P4501A2 (CYP1A2) is a key enzyme for activation of bladder carcinogens. Polymorphisms in the 5'-noncoding promoter region of CYP1A2 gene [mainly -2467T/delT(rs35694136) and -163C/A(rs762551)], are crucial in modifying CYP1A2 activity in smokers. Within the framework of a hospital-based case/control study, we investigated the relationship between CYP1A2 polymorphisms, occupational/environmental exposures and bladder cancer (BC) risk. The study population included 185 BC cases and 180 non-cancer controls, all Caucasian males. Data were collected on lifetime smoking, coffee drinking, dietary habits and lifetime occupation, with particular reference to exposure to aromatic amines (AAs) and polycyclic aromatic hydrocarbons (PAHs). A case-only design was applied to study the interaction between CYP1A2 -2467T/delT (or -163C/A) and occupational and environmental factors. Multiple logistic regression showed a significantly increased risk among heavy smokers (> or =50 packyears; OR 5.6, 95% CI: 2.5-12.5) and heavy coffee drinkers (>5 cups/day; OR 3.1, 95% CI: 1.2-7.9). Exposure to AAs showed a significant trend of BC risk with increasing cumulative exposure (CE) (P = 0.04), with heavy smoking as possible confounder. A decreased risk was noted for large leaf vegetable consumption, with significant trend from <1/month to >3 times/week (P = 0.008). The case-only analysis showed an interaction between -2467T/delT and tobacco smoking >25 packyears (P = 0.04); no interaction was detected between such polymorphisms and coffee consumption, dietary habits and occupational exposure to AAs. No effects were shown with -163C/A genotype as well as no overall effect of CYP1A2 by itself on BC risk. This is the first study suggesting that CYP1A2 -2467T/delT modifies the effect of cigarette smoking on BC risk.

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“…In this regard, two studies failed to find an impact of this SNP on either non-SCLC [Zienolddiny et al, 2008], adenocarcinoma [B'Chir et al, 2009], or SCC [B'Chir et al, 2009]. Conversely, a previous study showed an increased risk of SCC for carriers of the 22467delT variant, although that effect was observed only in a subset of seven individuals who were light smokers [Pavanello et al, 2007]. The 22467delT variant is present in the CYP1A2*1D allele, but it is also found in several other CYP1A2 haplotypes, four of which (CYP*1D, *1L, *1V, and *1W) were identified in the sample population.…”

Section: Discussionmentioning

confidence: 96%

“…Available data on the effect of CYP1A2 polymorphisms in lung cancer are scarce, especially in comparison with the bulk of studies on other genes involved in carcinogen activation/detoxification [Houlston, 2000;Raimondi et al, 2006;Chen et al, 2011;Cui et al, 2011]. Furthermore, contradictory results exist, with studies arguing both for [Pavanello et al, 2007;B'Chir et al, 2009;Singh et al, 2011] and against [Osawa et al, 2007;Zienolddiny et al, 2008] the involvement of CYP1A2 genetics in lung cancer. Our results show that only the 22467delT variant was moderately associated with risk for the disease.…”

Section: Discussionmentioning

confidence: 99%

Haplotypes in the 5′‐untranslated region of the CYP1A2gene are inversely associated with lung cancer risk but do not correlate with caffeine metabolism

Gervasini

Ghotbi

Aklillu

et al. 2012

Environ and Mol Mutagen

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In this study, we analyzed the influence of CYP1A2 genetic variation and enzyme activity on lung cancer risk in a high-incidence area. A total of 95 lung cancer patients and 196 controls were genotyped for the -3860G/A, -3113A/G, -2467T/delT, -739T/G, and -163C/A polymorphisms in the 5'-untranslated region of the gene. In addition, a subset of 70 patients and 115 controls were phenotyped by high-performance liquid chromatography determination of the caffeine metabolic ratio (CMR). The -2467T/delT polymorphism and the CYP1A2*1V haplotype (-163C>A, -2467T>delT) were inversely associated with lung cancer risk (odds ratio [OR] = 0.47 [0.2-0.9]; P = 0.02 and OR = 0.13 [0.02-1.0]; P = 0.04; respectively). In addition, the CYP*1A/*1V and *1F (-163C>A)/*1D (-163C>A, -2467T>delT) diplotypes were absent in the patients group, whereas accounting for 7.1% (P = 0.017) and 5.6% (P = 0.037) of controls, respectively. Mean CMR was significantly higher in patients than in controls (10.50 ± 17.31 vs. 6.52 ± 6.26, P = 0.01) but regression analyses did not yield significant ORs for the association with lung cancer risk. Similarly, no significant correlations were found between any genetic variant and enzyme activity. Several CYP1A2 haplotypes and diplotypes containing the -2467delT variant were associated with lower lung cancer risk; however, they did not correlate with significant changes in CYP1A2 metabolic activity toward caffeine.

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Interaction between CYP1A2-T2467DELT polymorphism and smoking in adenocarcinoma and squamous cell carcinoma of the lung

Cited by 24 publications

References 33 publications

Genetic Polymorphism of Metabolic Enzymes P450 (CYP) as a Susceptibility Factor for Drug Response, Toxicity, and Cancer Risk

Genetic Polymorphism of Metabolic Enzymes P450 (CYP) as a Susceptibility Factor for Drug Response, Toxicity, and Cancer Risk

CYP1A2 polymorphisms, occupational and environmental exposures and risk of bladder cancer

Haplotypes in the 5′‐untranslated region of the CYP1A2gene are inversely associated with lung cancer risk but do not correlate with caffeine metabolism

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