Dataset Information

Variant alleles of the CYP1B1 gene are associated with colorectal cancer susceptibility.

ABSTRACT: BACKGROUND: CYP1B1 is a P450 enzyme which is involved in the activation of pro-carcinogens to carcinogens as well as sex hormone metabolism. Because differences in the activity of the enzyme have been correlated with variant alleles of single nucleotide polymorphisms (SNPs), it represents an attractive candidate gene for studies into colorectal cancer susceptibility. METHODS: We genotyped 597 cancer patients and 597controls for three CYP1B1 SNPs, which have previously been shown to be associated with altered enzymatic activity. Using the three SNPs, eight different haplotypes were constructed. The haplotype frequencies were estimated in cases and controls and then compared. The odds ratio for each tumour type, associated with each haplotype was estimated, with reference to the most common haplotype observed in the controls. RESULTS: The three SNPs rs10012, rs1056827 and rs1056836 alone did not provide any significant evidence of association with colorectal cancer risk. Haplotypes of rs1056827 and rs10012 or rs1056827 and rs1056836 revealed an association with colorectal cancer which was significantly stronger in the homozygous carriers. One haplotype was under represented in the colorectal cancer patient group compared to the control population suggesting a protective effect. CONCLUSION: Genetic variants within the CYP1B1 that are associated with altered function appear to influence susceptibility to a colorectal cancer in Poland. Three haplotypes were associated with altered cancer risk; one conferred protection and two were associated with an increased risk of disease. These observations should be confirmed in other populations.

SUBMITTER: Trubicka J

PROVIDER: S-EPMC2929240 | biostudies-literature | 2010

REPOSITORIES: biostudies-literature

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Variant alleles of the CYP1B1 gene are associated with colorectal cancer susceptibility.

Trubicka Joanna J Grabowska-Kłujszo Ewa E Suchy Janina J Masojć Bartłomiej B Serrano-Fernandez Pablo P Kurzawski Grzegorz G Cybulski Cezary C Górski Bohdan B Huzarski Tomasz T Byrski Tomasz T Gronwald Jacek J Złowocka Elzbieta E Kładny Józef J Banaszkiewicz Zbigniew Z Wiśniowski Rafał R Kowalska Elzbieta E Lubinski Jan J Scott Rodney J RJ

BMC cancer 20100811

<h4>Background</h4>CYP1B1 is a P450 enzyme which is involved in the activation of pro-carcinogens to carcinogens as well as sex hormone metabolism. Because differences in the activity of the enzyme have been correlated with variant alleles of single nucleotide polymorphisms (SNPs), it represents an attractive candidate gene for studies into colorectal cancer susceptibility.<h4>Methods</h4>We genotyped 597 cancer patients and 597controls for three CYP1B1 SNPs, which have previously been shown to ...[more]

PMID: 20701755

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Project description:The aim of this study was to investigate the association between polymorphism of the cytochrome P450 1B1 (CYP1B1) gene, a metabolic enzyme gene, and the susceptibility to laryngeal cancer among the Chinese Han population.In a case-control study, we investigated polymorphisms in the CYP1B1 gene (rs10012, rs1056827, and rs1056836) with a real-time quantitative polymerase chain reaction (PCR) assay (TaqMan). The study was conducted with 300 Chinese Han patients with laryngeal cancer and 300 healthy Chinese Han subjects in a control group. We also studied the interactions between genetic polymorphism and risk factors such as smoking and alcohol consumption in the pathogenesis of laryngeal cancer.There were statistically significant differences in the distributions of the rs1056827 and rs1056836 genotypes between the 2 groups. Regarding rs1056827, carriers of the T allele had a significantly higher risk of laryngeal cancer than the G-allele carriers (OR=1.4339, 95% CI: 1.1268-1.8247; P=0.0034). The difference was still statistically significant after adjusting for factors such as age, sex, smoking, and drinking (adjusted OR=1.743, 95% CI: 1.124-3.743, P<0.001). However, regarding rs1056836, the G allele carriers had a significantly lower risk of laryngeal cancer than the C allele carriers (OR=0.5557, 95% CI: 0.3787-0.8154; P=0.0027). The difference was statistically significant even after adjusting for factors such as age, sex, smoking, and drinking (adjusted OR=0.5641, 95% CI: 0.3212-0.8121, P=0.001). Subjects who carry the C-T-C haplotype have a significantly increased incidence of laryngeal cancer. We also found that CYP1B1 rs1056827 polymorphism had synergistic effects with smoking or alcohol consumption regarding the risk of laryngeal cancer.CYP1B1 gene polymorphism is closely related to the onset of laryngeal cancer. There is a mutually synergistic effect between smoking, alcohol consumption, and CYP1B1 gene polymorphisms regarding laryngeal cancer.

Project description:BackgroundStudies investigating the association between single-nucleotide polymorphisms (SNPs) of the cytochrome P450 1B1 (CYP1B1) and prostate cancer (PCa) risk report conflicting results. To derive a more precise estimation of the relationship between CYP1B1 polymorphisms and PCa risk, a meta-analysis was performed.Methodology/principal findingsA comprehensive literature search was conducted to identify all eligible studies of CYP1B1 polymorphisms and PCa risk. A total of 14 independent studies, including 6380 cases and 5807 controls, were identified. We investigated by meta-analysis the effects of 5 polymorphisms in CYP1B1 L432V (12 studies, 5999 cases, 5438 controls), R48G (6 studies, 1647 cases, 1846 controls), N453S (4 studies, 1407 cases, 1499 controls), -13C/T (4 studies, 1116 cases, 1114 controls), and A119S (4 studies, 1057 cases, 1018 controls). There was no evidence that L432V had significant association with PCa in overall population. After subgroup analyses by ethnicity, we found that L432V was significantly associated with PCa risk in Asians (additive: OR?=?2.38, 95%CI?=?1.31-4.33, P?=?0.004; recessive: OR?=?2.11, 95%CI?=?1.17-3.79, P?=?0.01; dominant: OR?=?1.52, 95%CI?=?1.14-2.01, P?=?0.004; allelic: OR?=?1.52, 95%CI?=?1.20-1.92, P?=?0.0006). When stratified by source of controls, significantly elevated PCa risk was found in all genetic models in population based studies (additive: OR?=?1.34, 95%CI?=?1.14-1.57, P?=?0.0003; recessive: OR?=?1.25, 95%CI?=?1.09-1.43, P?=?0.002; dominant: OR?=?1.25, 95%CI?=?1.11-1.41, P?=?0.0002; allelic: OR?=?1.18, 95%CI?=?1.09-1.28, P<0.0001). For N453S, there was a significant association between N453S polymorphism and PCa risk in both overall population (dominant: OR?=?1.18, 95%CI?=?1.00-1.38, P?=?0.04) and mixed population (domiant: OR?=?1.31, 95%CI?=?1.06-1.63, P?=?0.01; allelic: OR?=?1.27, 95%CI?=?1.05-1.54, P?=?0.01). For A119S, our analysis suggested that A119S was associated with PCa risk under recessive model in overall population (OR?=?1.37, 95%CI?=?1.04-1.80, P?=?0.03).ConclusionsThe results suggest that L432V, N453S, and A119S polymorphisms of CYP1B1 might be associated with the susceptibility of PCa. Further larger and well-designed multicenter studies are warranted to validate these findings.

Dataset Information

Variant alleles of the CYP1B1 gene are associated with colorectal cancer susceptibility.

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Variant alleles of the CYP1B1 gene are associated with colorectal cancer susceptibility.

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