Liang Ying, Han Wen, Yan Hongwei, Mao Qiqi
Department of Clinical Laboratory, First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi, China.
Institute of Information and Management, Guangxi Medical University, Nanning, Guangxi, China.
J Cancer Res Ther. 2018 Jun;14(Supplement):S463-S467. doi: 10.4103/0976-7800.179173.
The CYP3A53 allele (A6986G transition in intron 3) is the major member of cytochrome P450 subfamily, which plays a pivotal role in exogenous carcinogens of liver. Variation of the CYP3A53 (rs776746 A > G) can lead to oxidation and inactivation of testosterone, which may result in individual susceptibility to prostate cancer.
All eligible published studies about association between CYP3A5*3 polymorphisms and prostate cancer risk were searched in PubMed, Embase, Web of Science, and Cochrane Library, for the period up to August 2015. Odds ratios (ORs) together with 95% confidence intervals (95% CIs) were used to access the strength of the association.
Six case-control studies including 2522 cancer patients and 2444 healthy controls were finally included. The meta-analysis results suggested that CYP3A53 polymorphisms were significantly associated with an increased risk of prostate cancer under two genetic models (GG + AG vs. AA: OR = 1.53, 95% CI = 1.23-1.90, P = 0.000; GG vs. AA: OR = 1.46, 95% CI = 1.14-1.87, P = 0.000). Further subgroup analysis according to ethnicity indicated that CYP3A53 polymorphism may increase the risks of prostate cancer among African (G allele vs. A allele: OR = 1.34, 95% CI = 1.14-1.57, P = 0.000; GG + AG vs. AA: OR = 1.606, 95% CI = 1.27-2.04, P = 0.000). Sensitivity analysis indicated a reliable result and publication bias suggested no strong publication bias under the genetic models.
Our data support that the CYP3A5*3 polymorphism may be associated with increased risk of prostate cancer, particularly in African populations. Large and well-designed studies are needed to validate this association.
细胞色素P450亚家族主要成员CYP3A53等位基因(第3内含子A6986G转换)在肝脏外源性致癌物中起关键作用。CYP3A53(rs776746 A>G)变异可导致睾酮氧化失活,这可能导致个体对前列腺癌易感。
检索截至2015年8月的PubMed、Embase、Web of Science和Cochrane图书馆中所有关于CYP3A5*3基因多态性与前列腺癌风险关联的符合条件的已发表研究。采用比值比(OR)及95%置信区间(95%CI)评估关联强度。
最终纳入6项病例对照研究,包括2522例癌症患者和2444例健康对照。荟萃分析结果表明,在两种遗传模型下,CYP3A53基因多态性与前列腺癌风险增加显著相关(GG+AG vs. AA:OR=1.53,95%CI=1.23-1.90,P=0.000;GG vs. AA:OR=1.46,95%CI=1.14-1.87,P=0.000)。根据种族进行的进一步亚组分析表明,CYP3A53基因多态性可能增加非洲人患前列腺癌的风险(G等位基因vs. A等位基因:OR=1.34,95%CI=1.14-1.57,P=0.000;GG+AG vs. AA:OR=1.606,95%CI=1.27-2.04,P=0.000)。敏感性分析表明结果可靠,发表偏倚提示在遗传模型下无明显发表偏倚。
我们的数据支持CYP3A5*3基因多态性可能与前列腺癌风险增加相关,尤其是在非洲人群中。需要进行大规模、设计良好的研究来验证这种关联。