Quantitative Assessment of the Influence of Cytochrome P450 1A2 Gene Polymorphism and Colorectal Cancer Risk

Abstract

Cytochrome P450 1A2 (CYP1A2) 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 colorectal cancer (CRC). The CYP1A2*C (rs2069514) and CYP1A2*F (rs762551) polymorphism are two of the most commonly studied polymorphisms of the gene for their association with risk of CRC, but the results are conflicting. To derive a more precise estimation of the relationship between CYP1A2 and genetic risk of CRC, we performed a comprehensive meta-analysis which included 7088 cases and 7568 controls from 12 published case-control studies. In a combined analysis, the summary per-allele odds ratio for CRC was 0.91 (95% CI: 0.83–1.00, P = 0.04), and 0.91 (95% CI: 0.68–1.22, P = 0.53), for CYP1A2 *F and *C allele, respectively. In the subgroup analysis by ethnicity, significant associations were found in Asians for CYP1A2*F and CYP1A2*C, while no significant associations were detected among Caucasian populations. Similar results were also observed using dominant genetic model. Potential sources of heterogeneity were explored by subgroup analysis and meta-regression. No significant heterogeneity was detected in most of comparisons. This meta-analysis suggests that the CYP1A2 *F and *C polymorphism is a protective factor against CRC among Asians.

Caffeine Cytochrome P450 1A2 Metabolic Phenotype Does Not Predict the Metabolism of Heterocyclic Aromatic Amines in Humans

“…26-28,30,64 The expression of hepatic P450 1A2 is highly variable in humans. Both genetic and environmental factors influence the inducibility of the enzyme and the level of protein expression.…”

“…Collectively, the data from the studies have been inconsistent with no clear association found for any genetic polymorphisms in carcinogen metabolism enzymes and cancer risk. 26-31 A major limiting factor in the risk assessment is the uncertainty in quantitative estimates of chronic exposure to HAAs. 32 Some of the inconsistency also may be that the different genotypes in metabolizing enzymes do not accurately reflect appreciable changes in the level of protein expression or the phenotypic activity of the enzymes.…”

Genetic polymorphisms in cytochrome P450 and clinical outcomes of FOLFIRI chemotherapy in patients with metastatic colorectal cancer

“…The reasons may be genotyping errors, limited sample size, or that these SNPs are associated with the risk of colorectal cancer. As far as we know, CYP1A2 rs2069514 G>A has been confirmed by meta-analysis to be related to the risk of colorectal cancer in Asia [35]. But there is no report whether the other two SNPs are associated with the incidence of colorectal cancer.…”

Low penetrance genetic polymorphisms as potential biomarkers for colorectal cancer predisposition

“…For the CYP1A2 gene, two polymorphisms which have been the focus of widespread attention are the c.‐9‐154C>A (rs762551) polymorphism (conventionally known as the ‐164A>C or ‐163C>A polymorphism) and the rs2069514 (also known as the 3858G>A polymorphism). One meta‐analysis involving 11 studies with 6370 cases and 6837 controls showed a risk association of the rs762551 polymorphism, although with borderline significance . Another meta‐analysis of an overlapping set of 11 studies showed a lack of significant of the polymorphism .…”