Genetic polymorphisms of cytochrome P450 in patients with hepatitis C virus‐associated hepatocellular carcinoma

Mochizuki, Junko; Murakami, S; Sanjo, Akira; Takagi, Ichiro; Akizuki, Setsuko; Ohnishi, Akihiro

doi:10.1111/j.1440-1746.2005.03808.x

Cited by 19 publications

(9 citation statements)

References 44 publications

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“…Among the 71 included studies, 42 were population-based case-control studies, 28 hospital-based case-control studies and one genome-wide association study, including total of 47,413 cancer cases and 58,546 controls (Table 1 ). The total investigated SNPs were six, of which 62 studies on the rs762551 [ 4 , 7 – 21 , 23 , 24 , 26 – 46 , 48 – 50 , 52 , 61 – 65 , 67 , 68 , 72 – 75 , 77 – 79 , 81 – 84 ]. Thirty five studies out of 62 were conducted on Caucasians (56.5 %), 17 on mixed populations (27.4 %) and 10 on Asians (16.1 %), including 33,181 cancer cases and 40,195 controls.…”

Section: Resultsmentioning

confidence: 99%

Lack of association between polymorphisms in the CYP1A2 gene and risk of cancer: evidence from meta-analyses

et al. 2016

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BackgroundPolymorphisms in the CYP1A2 genes have the potential to affect the individual capacity to convert pre-carcinogens into carcinogens. With these comprehensive meta-analyses, we aimed to provide a quantitative assessment of the association between the published genetic association studies on CYP1A2 single nucleotide polymorphisms (SNPs) and the risk of cancer.MethodsWe searched MEDLINE, ISI Web of Science and SCOPUS bibliographic online databases and databases of genome-wide association studies (GWAS). After data extraction, we calculated Odds Ratios (ORs) and 95 % confidence intervals (CIs) for the association between the retrieved CYP1A2 SNPs and cancer. Random effect model was used to calculate the pooled ORs. Begg and Egger tests, one-way sensitivity analysis were performed, when appropriate. We conducted stratified analyses by study design, sample size, ethnicity and tumour site.ResultsSeventy case-control studies and one GWA study detailing on six different SNPs were included. Among the 71 included studies, 42 were population-based case-control studies, 28 hospital-based case-control studies and one genome-wide association study, including total of 47,413 cancer cases and 58,546 controls. The meta-analysis of 62 studies on rs762551, reported an OR of 1.03 (95 % CI, 0.96–1.12) for overall cancer (P for heterogeneity < 0.01; I2 = 50.4 %). When stratifying for tumour site, an OR of 0.84 (95 % CI, 0.70–1.01; P for heterogeneity = 0.23, I2 = 28.5 %) was reported for bladder cancer for those homozygous mutant of rs762551. An OR of 0.79 (95 % CI, 0.65–0.95; P for heterogeneity = 0.09, I2 = 58.1 %) was obtained for the bladder cancer from the hospital-based studies and on Caucasians.ConclusionsThis large meta-analysis suggests no significant effect of the investigated CYP1A2 SNPs on cancer overall risk under various genetic models. However, when stratifying according to the tumour site, our results showed a borderline not significant OR of 0.84 (95 % CI, 0.70–1.01) for bladder cancer for those homozygous mutant of rs762551. Due to the limitations of our meta-analyses, the results should be interpreted with attention and need to be further confirmed by high-quality studies, for all the potential CYP1A2 SNPs.

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Section: Resultsmentioning

confidence: 99%

Lack of association between polymorphisms in the CYP1A2 gene and risk of cancer: evidence from meta-analyses

et al. 2016

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“…Above all, ethnic differences may attribute to these different results, since the distributions of the CYP2C19 polymorphism were different between various ethnic populations. For instance, the frequencies of CYP2C19*3 polymorphism allele differs from less than 0.5% in Caucasian population [36], 12% in Chinese population [22], to 16% in Japanese populations [17]. However, several studies conducted among Middle East populations which shown a similar PMs genotypes prevalence as Caucasians found a significant association between CYP2C19 PMs genotype and cancer susceptibility [21,27].…”

Section: Discussionmentioning

confidence: 99%

Poor Metabolizers at the Cytochrome P450 2C19 Loci Is at Increased Risk of Developing Cancer in Asian Populations

et al. 2013

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BackgroundCYP2C19 encodes a member of the cytochrome P450 superfamily of enzymes, which play a central role in activating and detoxifying many carcinogens and endogenous compounds thought to be involved in the development of cancer. In the past decade, two common polymorphisms among CYP2C19 (CYP2C19*2 and CYP2C19*3) that are responsible for the poor metabolizers (PMs) phenotype in humans and cancer susceptibility have been investigated extensively; however, these studies have yielded contradictory results.Methods and ResultsTo investigate this inconsistency, we conducted a comprehensive meta-analysis of 11,554 cases and 16,592 controls from 30 case-control studies. Overall, the odds ratio (OR) of cancer was 1.52 [95% confidence interval (CI): 1.23–1.88, P<10-4] for CYP2C19 PMs genotypes. However, this significant association vanished when the analyses were restricted to 5 larger studies (no. of cases ≥ 500 cases). In the subgroup analysis for different cancer types, PMs genotypes had an effect of increasing the risks of esophagus cancer, gastric cancer, lung cancer and hepatocellular carcinoma as well as head neck cancer. Significant results were found in Asian populations when stratiﬁed by ethnicity; whereas no significant associations were found among Caucasians. Stratiﬁed analyses according to source of controls, significant associations were found only in hospital base controls.ConclusionsOur meta-analysis suggests that the CYP2C19 PMs genotypes most likely contributes to cancer susceptibility, particularly in the Asian populations.

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“…In fact, Kondoh et al (1999) reported that CYP3A4 mRNA is highly induced in nontumorous liver and maintained at variable levels in carcinoma tissues from hepatocarcinoma patients but barely detectable in normal liver from non hepatocarcinoma patients. Moreover, genetic alterations of CYPs have been reported in the development and/or progression of a subset of various cancers (Mochizuki et al, 2005;Shin et al, 2007). However, factors regulating CYP3A activity and expression have been remained limited.…”

Section: Discussionmentioning

confidence: 99%

An NH2-terminal truncated cytochrome P450 CYP3A4 showing catalytic activity is present in the cytoplasm of human liver cells

et al. 2008

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Cytochrome P450 3A4 (CYP3A4), is the dominant human liver hemoprotein enzyme localized in the endoplasmic reticulum (ER), and is responsible for the metabolism of more than 50% of clinically relevant drugs. While we were studying CYP3A4 expression and activity in human liver, we found that anti-CYP3A4 antibody cross-reacted with a lower band in liver cytoplasmic fraction. We assessed the activities of CYP3A4 and its truncated form in the microsomal and cytoplasmic fraction, respectively. In the cytoplasmic fraction, truncated CYP3A4 showed catalytic activity when reconstituted with NADPH-cytochrome P-450 reductase and cytochrome b5. In order to determine which site was deleted in the truncated form in vitro, we transfected cells with N-terminal tagged or C-terminal tagged human CYP3A4 cDNA. The truncated CYP3A4 is the N-terminal deleted form and was present in the soluble cytoplasmic fraction. Our result shows, for the first time, that N-terminal truncated, catalytically active CYP3A4 is present principally in the cytoplasm of human liver cells.

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Genetic polymorphisms of cytochrome P450 in patients with hepatitis C virus‐associated hepatocellular carcinoma

Cited by 19 publications

References 44 publications

Lack of association between polymorphisms in the CYP1A2 gene and risk of cancer: evidence from meta-analyses

Lack of association between polymorphisms in the CYP1A2 gene and risk of cancer: evidence from meta-analyses

Poor Metabolizers at the Cytochrome P450 2C19 Loci Is at Increased Risk of Developing Cancer in Asian Populations

An NH2-terminal truncated cytochrome P450 CYP3A4 showing catalytic activity is present in the cytoplasm of human liver cells

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