Department of Urology, Tianjin Medical University General Hospital, Tianjin, 300052, China.
Department of Urology, Linzi District People's Hospital, Zibo 255400, China.
Gene. 2020 Oct 5;757:144924. doi: 10.1016/j.gene.2020.144924. Epub 2020 Jul 2.
N-acetyltransferase 2 (NAT2) polymorphism could participate in the metabolism of carcinogens through regulating the activity of a series of critical enzymes. However, the effects of NAT2 polymorphism on bladder cancer (BCa) risk were still inconclusive. In order to illustrate whether NAT2 polymorphism may influence the susceptibility to BCa, we conducted this updated meta-analysis.
Databases including PubMed, Medline, Embase, Web of Science, Cochrane Library, and China National Knowledge Infrastructure(CNKI) were systematically retrieved and we applied MetaGenyo to perform final meta-analysis. Odds ratios (ORs) as well as 95% confidence intervals (CIs) were calculated and Bonferroni method was applied to correct the P-value for multiple comparisons. The registration of this study protocol is at PROSPERO and ID is CRD42019133957.
Ultimately, 54 case-control studies were identified for final meta-analysis (13343 BCa cases and 18,586 controls). Overall analysis indicated that the slow genotype in NAT2 polymorphism was obviously associated with BCa risk (P < 0.001). Subgroup analyses demonstrated that significant risk with the slow genotype was observed in Caucasians, Asians, smokers, non-exposed individuals, high grade bladder cancer (HGBC) patients and muscle-invasive bladder cancer (MIBC) patients. In addition, the intermediate NAT2 genotype was revealed to increase the BCa risk of Asians and transitional cell carcinoma (TCC) patients. However, no correlation was identified in Africans with the NAT2 polymorphism.
The slow NAT2 genotype was identified to be the risk genotype for BCa. The intermediate genotype could serve as the candidate risk genotype. The gene-smoking interaction with NAT2 polymorphism might accelerate the tumor progression.
N-乙酰基转移酶 2（NAT2）多态性可通过调节一系列关键酶的活性参与致癌物的代谢。然而，NAT2 多态性对膀胱癌（BCa）风险的影响仍不确定。为了阐明 NAT2 多态性是否可能影响 BCa 的易感性，我们进行了这项更新的荟萃分析。
系统检索了 PubMed、Medline、Embase、Web of Science、Cochrane Library 和中国知网（CNKI）等数据库，并应用 MetaGenyo 进行最终的荟萃分析。计算了比值比（OR）及其 95%置信区间（CI），并应用 Bonferroni 方法校正了多重比较的 P 值。本研究方案的注册在 PROSPERO 上进行，ID 为 CRD42019133957。
最终有 54 项病例对照研究纳入最终的荟萃分析（13343 例 BCa 病例和 18586 例对照）。总体分析表明，NAT2 多态性中的慢基因型与 BCa 风险明显相关（P<0.001）。亚组分析表明，在白种人、亚洲人、吸烟者、非暴露人群、高级别膀胱癌（HGBC）患者和肌层浸润性膀胱癌（MIBC）患者中，存在明显的慢基因型与风险相关。此外，中间 NAT2 基因型被发现增加了亚洲人和移行细胞癌（TCC）患者的 BCa 风险。然而，在非洲人中没有发现 NAT2 多态性与膀胱癌之间的相关性。
慢 NAT2 基因型被确定为 BCa 的风险基因型。中间基因型可能是候选风险基因型。NAT2 多态性与基因-吸烟的相互作用可能会加速肿瘤的进展。
