Coffee consumption and risk of lung cancer: a meta-analysis.
ABSTRACT Epidemiologic studies have evaluated the potential association between coffee consumption and lung cancer risk. However, results were inconsistent. To clarify the role of coffee in lung cancer, we conducted a meta-analysis on this topic. We searched PubMed and EMBASE databases (from 1966 to January 2009) and the reference lists of retrieved articles. Study-specific risk estimates were pooled using random-effects model. Five prospective studies and 8 case-control studies involving 5347 lung cancer cases and 104,911 non-cases were included in this meta-analysis. The combined results indicated a significant positive association between highest coffee intake and lung cancer [relative risk (RR)=1.27, 95% confidence interval (CI)=1.04-1.54). Furthermore, an increase in coffee consumption of 2 cups/day was associated with a 14% increased risk of developing lung cancer (RR=1.14, 95% CI=1.04-1.26). In stratified analyses, the highest coffee consumption was significantly associated with increased risk of lung cancer in prospective studies, studies conducted in America and Japan, but borderline significantly associated with decreased risk of lung cancer in non-smokers. In addition, decaffeinated coffee drinking was associated with decreased lung cancer risk, although the number of studies on this topic was relative small. In conclusion, results from this meta-analysis indicate that high or an increased consumption of coffee may increase the risk of lung cancer. Because the residual confounding effects of smoking or other factors may still exist, these results should be interpreted with caution.
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ABSTRACT: It has been proposed that p53 tumor-suppressor plays a key role in maintaining genome integrity in mammalian cells. We analyzed karyotype alterations in human and murine cell sublines expressing various exogenous human mutant (His175, Trp248, His273) or wild-type (wt) p53 cDNAs. In human pseudodiploid LIM1215 cells that contain two endogenous wt-p53 gene alleles, p53 mutants caused both an increase in the frequency of chromosome breaks and an emergence of hyperdiploid cells. Murine T12-/- and 10(1) fibroblasts lacking endogenous p53 expression have very unstable karyotypes and show a strong tendency to increase their ploidy levels during growth in culture. Transduction of a wt-p53 construct into p53-deficient cells inhibited an accumulation of highly polyploid cell variants. Transduction of mutant p53 did not show such an effect. Modification of endogenous and exogenous p53 expression by caffeine, which interferes with normal induction of p53 in response to DNA damage, showed no correlation between the induction of chromosome breaks and heteroploidy. We conclude that the caffeine- or mutant p53-induced increase in the frequency of chromosomal breaks in dividing LIM1215 cells is assonated with inactivation of wt-p53 function(s) responsible for control of G1 checkpoint and/or DNA repair, while numerical chromosome changes in these cells may be a result of elimination or modification of a separate p53 function, or due to gain-of-function activities of p53 mutants. p53 modifications may therefore cause chromosome instability by different pathways: (1) through changes in the system(s) preventing proliferation of cells with genomic alterations; and (2) by increasing the probability of events, such as chromosome non-disjunction and/or endoreduplication that can lead to chromosome gains.Mutation Research/Fundamental and Molecular Mechanisms of Mutagenesis 08/1996; 354(1):129-38. · 3.90 Impact Factor
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ABSTRACT: Caffeine metabolism by hepatic microsomal P450 enzymes is well documented in experimental animals and humans. However, its induction effect on P450 enzymes has not been thoroughly studied. In a preliminary experiment, the time-dependent incubation of 1 mM caffeine with rat hepatocyte culture resulted in an increase of its own metabolic rate. The dose-dependent expression of rat hepatic and renal cytochromes (CYP) 1A1/1A2 was then investigated after per os administration of caffeine. P450 expression was monitored by using specific enzymatic activities and Northern blot analysis. Caffeine caused a dose-dependent elevation of hepatic CYP1A1/1A2 activities in microsomal preparations, which ranged from 1.7- to 6-fold for ethoxyresorufin O-deethylase and 3- to 8.9-fold for methoxy-resorufin O-demethylase according to the dose regimen of 50 and 150 mg caffeine/kg/day for 3 days, respectively. Northern blot analysis demonstrated that caffeine treatment increased liver CYP1A1 and CYP1A2 mRNA levels over the dose regimen of 50–150 mg caffeine/kg/day for 3 days, respectively. The result of this study demonstrates that caffeine increases its own metabolism in a dosedependent manner and induces CYP1A1/1A2 expression through either transcriptional activation or mRNA stabilization.Biochemical Pharmacology 01/1997; 52(12):1915-1919. · 4.58 Impact Factor
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ABSTRACT: We have studied the effect of caffeine on gene- and strand-specific DNA repair after exposure of Chinese hamster ovary cells and human xeroderma pigmentosum complementation group C (XPC) cells to ultraviolet irradiation (UV). In hamster cells, caffeine inhibited the repair of cyclobutane dimers (CPDs) in the dihydrofolate reductase (DHFR) gene by up to 66% after 8 h of repair incubation. This effect was dose-dependent, with more inhibition at 10 than at 1.5 mM caffeine. The inhibition was due to decreased repair in the transcribed strand of the hamster DHFR gene. This decrease in repair of CPDs in the DHFR gene correlated with an enhancement of UV-induced cell killing by caffeine. DNA repair was also measured in the overall genome by repair-replication analysis. In hamster cells, caffeine caused a modest enhancement of repair. Caffeine did not produce a significant effect on cell cycle progression up to 8 h after UV irradiation, but it caused a distinct block in early S phase during the 24 h post-irradiation period. In XPC cells, 10 mM caffeine inhibited the removal of CPDs from the transcribed strand of the DHFR gene by 92%. The removal of all photoproducts from the overall genome was inhibited by 26% in these cells. Since the residual repair in XPC cells is thought to occur in active genomic regions, we propose that caffeine preferentially inhibits gene-specific repair.Carcinogenesis 06/1995; 16(5):1149-55. · 5.64 Impact Factor