Bladder cancer (BCa) is an exophytic tumor that presents as either noninvasive confined to the mucosa (NMIBC) or invading the detrusor muscle (MIBC), and was recently further subgrouped into molecular subtypes. Arylamines, major BCa environmental and occupational risk factors, are mainly metabolized by the genetically polymorphic N‐acetyltransferases 1, NAT1  and NAT2 . In this study, we investigated the association between N‐acetyltransferases genetic polymorphism and key MIBC and NMIBC tumor biomarkers and subtypes. A cohort of 250 males with histologically confirmed urothelial BCa was identified. Tumors were genotyped for NAT1 and NAT2 using real‐time polymerase chain reaction (PCR), and characterized for mutations in TP53, RB1 , and FGFR3 by PCR‐restriction fragment length polymorphism. Pathology data and patients' smoking status were obtained from medical records. Pearson χ ² and Fisher exact tests were used to check for associations and interactions. Results show that NAT1 G⁵⁶⁰A polymorphism is significantly associated with higher muscle‐invasiveness (MIBC vs NMIBC; P  = .001), higher tumor grade (high grade vs low grade; P  = .011), and higher FGFR3 mutation frequency within the MIBC subgroup (P = .042; .027). NAT2 G⁸⁵⁷A polymorphism is also found to be significantly associated with higher muscle‐invasiveness (MIBC vs NMIBC; P  = .041). Our results indicate that slow N‐acetylation is a contributor to bladder carcinogenesis and muscle‐invasiveness. These findings highlight NAT1 as a biomarker candidate in BCa and a potential target for drug development.

中文翻译：

---

缓慢的N-乙酰化可能是导致膀胱癌发生的原因。

膀胱癌（BCa）是一种外生性肿瘤，以无创性局限于粘膜（NMIBC）或侵犯逼尿肌（MIBC）出现，最近被进一步细分为分子亚型。芳香胺是BCA的主要环境和职业危险因素，主要由遗传多态性N乙酰转移酶1，  NAT1 和NAT2代谢。在这项研究中，我们调查了N-乙酰基转移酶基因多态性与关键MIBC和NMIBC肿瘤生物标记物和亚型之间的关系。鉴定了250名经组织学证实尿路上皮BCa的男性。对NAT1和NAT2的肿瘤进行基因分型使用实时聚合酶链反应（PCR），并通过PCR限制性片段长度多态性表征TP53，RB1和FGFR3中的突变。从病历中获取病理数据和患者吸烟状况。皮尔逊χ ²和Fisher精确测试是用来检查关联和相互作用。结果显示NAT1 G ⁵⁶⁰ A多态性与较高的肌肉侵袭性（MIBC vs NMIBC; P  = .001），较高的肿瘤等级（高等级与低等级; P  = .011）和FGFR3突变频率较高相关。 MIBC亚组（P = .042; .027）。NAT2 G ⁸⁵⁷ A多态性也被发现与更高的肌肉侵袭性显着相关（MIBC vs NMIBC；P  = .041）。我们的研究结果表明，缓慢的N乙酰化是膀胱癌发生和肌肉侵袭的原因。这些发现强调了NAT1作为BCa中的生物标志物候选物和药物开发的潜在靶标。