CYP3A5*3 polymorphism and cancer risk: a meta-analysis and meta-regression

Abstract

CYP3A5 is a cytochrome P450 superfamily member which is involved in the metabolism of drugs, steroid hormones, and other xenobiotics. Emerging evidences suggest that CYP3A5*3 (rs776746 A>G) polymorphism may play a role in the etiology of carcinogenesis and affect an individual's susceptibility to cancer in humans, but individually published studies showed inconclusive results. This meta-analysis aimed to derive a more accurate estimation of the correlation between CYP3A5*3 polymorphism and cancer risk. A literature search of PubMed, Embase, Web of Science, and China BioMedicine databases was conducted on articles published before January 1, 2013. Seventeen case-control studies were included with a total of 7,458 cancer patients and 7,166 healthy controls. The meta-analysis results showed that CYP3A5*3 polymorphism may increase the risk of cancer, especially in acute leukemia, chronic leukemia, and colorectal cancer. However, no statistically significant associations were found in prostate cancer, liver cancer, and other cancers. Further subgroup analysis by ethnicity indicated that CYP3A5*3 polymorphism was associated with an increased risk of cancer among Asian and Caucasian populations, but not among African populations. In conclusion, the current meta-analysis suggests that CYP3A5*3 polymorphism may play an important role in the development of acute and chronic leukemia and colorectal cancer, especially among Asian and Caucasian populations.

CYP3A5*3Polymorphism and Its Clinical Implications and Pharmacokinetic Role

“…[30,31] Based on the assumption that CYP3A5 plays a role in the modulation of steroid hormone levels, many scientists have evaluated the role of CYP3A5 polymorphisms in cancer risk, including in the following cancers: acute or chronic leukemia, prostate cancer, colorectal cancer, gastric cancer, esophageal cancer, testicular cancer, and breast cancer. [16,[32][33][34][35][36][37][38] A recent meta-analysis revealed that CYP3A5*3 polymorphism may increase the risks of acute leukemia, chronic leukemia, and colorectal cancers. [33] However, no evidence was found of association in prostate cancer, liver cancer, and other cancers with CYP3A5*3 polymorphisms.…”

“…[16,[32][33][34][35][36][37][38] A recent meta-analysis revealed that CYP3A5*3 polymorphism may increase the risks of acute leukemia, chronic leukemia, and colorectal cancers. [33] However, no evidence was found of association in prostate cancer, liver cancer, and other cancers with CYP3A5*3 polymorphisms. Additionally, the finding was more striking among Asian and Caucasian populations, suggesting ethnic differences in the occurrence of cancers.…”

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

“…So far, at least 34 SNPs of the CYP3A5 gene have been identified [27]. Among them, the most frequent and functional polymorphism is the A to G transition in intron 3 at position 6986 (CYP3A5*3, rs776746 A>G), which can result in a truncated protein with fully lost enzyme activity [27].…”

“…So far, at least 34 SNPs of the CYP3A5 gene have been identified [27]. Among them, the most frequent and functional polymorphism is the A to G transition in intron 3 at position 6986 (CYP3A5*3, rs776746 A>G), which can result in a truncated protein with fully lost enzyme activity [27]. Because CYP450 participated in inactivation process of irinotecan, it is reasonable to hypothesize that due to abolished function, the homozygous mutated variant (GG) genotype cannot deactivate irinotecan, which results in the accumulation of the drug in vivo and, thus, leads to higher response rate and longer PFS.…”

“…CYP3A5*3 polymorphism may also play a critical role in determining an individual's susceptibility to cancer at various sites, owing to involvement of the metabolism of exogenous carcinogens. Based on the meta-analysis, CYP3A5*3 polymorphism may increase the risk of acute leukemia, chronic leukemia, and colorectal cancer, but not prostate cancer, liver cancer, or other cancers [27].…”