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

Abstract

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.

Meta-analysis of the CYP1A2 -163C＞A Polymorphism and Lung Cancer Risk

“…After deleted duplicate and non-relevant studies, finally seven casecontrol studies (Gemignani et al, 2007;Osawa et al, 2007;Zienolddiny et al, 2008;Aldrich et al, 2009;B'Chir et al, 2009;Singh et al, 2010;Gervasini et al, 2013) and one nested case-control study (Pavanello et al, 2012) involving 1675 lung cancer patients and 2393 controls were included.…”

“…Lung cancer is one of the six different cancers in this meta-analysis; however, there are histopathological types of lung cancer and different cancer site of body has its histological properties. In addition, there are three studies (Zienolddiny et al, 2008;Pavanello et al, 2012;Gervasini et al, 2013) investigate CYP1A2 -163 C>A polymorphism and risk of lung cancer have been searched since the meta-analysis (Wang et al, 2012). Thus, we performed this meta-analysis to address the association between CYP1A2 -163 C>A polymorphism and overall and subgroups risk in the development of lung cancer.…”

Meta-analysis of correlation between the CYP1A2 -3860 G > A polymorphism and lung cancer risk

“…A previous study estimated approximately 228,190 people to be diagnosed with lung cancer, as well as 159,480 lung cancer-related deaths to occur, in 2013 in the United States alone (Gervasini et al, 2013). Lung cancer is a fatal disease with a complex carcinogenesis.…”

“…A systematic database search and manual review of the reference lists in eligible studies yielded a total of 119 publications; these were rigorously analyzed by the reviewers for conformance with the inclusion criteria, leading to the selection of six articles, comprising 1168 lung cancer patients and 1598 controls, for this meta-analysis (Osawa et al, 2007;Zienolddiny et al, 2008;B'chir et al, 2009;Singh et al, 2010Singh et al, -2011Pavanello et al, 2012;Gervasini et al, 2013). The year of publication of these studies ranged from 2007 to 2013.…”

The perspective of caffeine and caffeine derived compounds in therapy

“…The meaning of caffeine ability to inhibit poly(ADP-ribose)polymerase is not fully explored. Though some apprehensions that caffeine would initiate cancer were stated in the past, clinical tests either did notconfi rm or even excluded the hypothesis (78). Contrary, some anti-cancer effects of caffeine are mentioned in the current literature (79,80).…”