Abstract
BackgroundCytochrome P450 1A1 (CYP1A1) is a member of the CYP1 family, which is a key enzyme in the metabolism of many endogenous substrates and exogenous carcinogens. To date, many studies have examined the association between CYP1A1 MspI and Ile462Val polymorphisms and cancer risk in various populations, but their results have been conflicting rather than consistent.MethodsTo assess this relationship more precisely, a meta-analysis based on 198 publications was performed. Odds ratios (OR) and corresponding 95% confidence intervals (CIs) were used to assess the association. The statistical heterogeneity across studies was examined with a chi-square-based Q-test.ResultsOverall, a significant elevated risk of cancer was associated with CYP1A1 MspI and Ile462Val polymorphisms for all genetic models studied. Further stratified analysis by cancer types revealed that the MspI polymorphism may increase the risk of lung cancer and cervical cancer whereas the Ile462Val polymorphism may contribute to a higher risk of lung cancer, leukemia, esophageal carcinoma, and prostate cancer. In the subgroup analysis by ethnicity, obvious associations were found in the Asian population for the MspI polymorphism while an increased risk of cancer was observed in Asians and Caucasians for the Ile462Val polymorphism.ConclusionsThe results of this meta-analysis suggest that CYP1A1 MspI and Ile462Val polymorphisms contribute to increased cancer susceptibility among Asians. Additional comprehensive system analyses are required to validate this association and other related polymorphisms.
Highlights
Cytochromes P450 (CYP450s) are heme-containing enzymes important to phase I-dependent metabolism of drugs and other xenobiotics [1]
There were 32 lung cancer studies, 29 breast cancer studies, 15 leukemia studies, 10 prostate cancer studies, 10 head and neck cancer studies, 9 colorectal cancer studies, 7 endometrial cancer studies, 6 cervical cancer studies, 5 ovarian cancer studies, 4 gastric cancer studies, 4 esophageal carcinoma studies, 3 hepatocellular cancer studies, 3 lymphoma studies and other cancers were categorized into the “others” group
There were 26 lung cancer studies, 25 breast cancer studies, 8 leukemia studies, 9 prostate cancer studies, 12 head and neck cancer studies, 8 colorectal cancer studies, 6 endometrial cancer studies, 3 cervical cancer studies, 4 ovarian cancer studies, 4 gastric cancer studies, 10 esophageal carcinoma studies, 3 hepatocellular cancer studies, 6 oral cancer studies and other cancers were categorized into the “others” group
Summary
Cytochromes P450 (CYP450s) are heme-containing enzymes important to phase I-dependent metabolism of drugs and other xenobiotics [1]. Cytochrome P450 1A1 (CYP1A1) is a member of the CYP1 family, which is a key enzyme in the metabolism of many endogenous substrates and exogenous carcinogens. Many studies have examined the association between CYP1A1 MspI and Ile462Val polymorphisms and cancer risk in various populations, but their results have been conflicting rather than consistent. Results: Overall, a significant elevated risk of cancer was associated with CYP1A1 MspI and Ile462Val polymorphisms for all genetic models studied. In the subgroup analysis by ethnicity, obvious associations were found in the Asian population for the MspI polymorphism while an increased risk of cancer was observed in Asians and Caucasians for the Ile462Val polymorphism. Conclusions: The results of this meta-analysis suggest that CYP1A1 MspI and Ile462Val polymorphisms contribute to increased cancer susceptibility among Asians. Additional comprehensive system analyses are required to validate this association and other related polymorphisms
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