Urology Department, University Hospital Fuenlabrada, Fuenlabrada, Madrid, Spain.
Urology Department, University Hospital Virgen de las Nieves, Av. de las Fuerzas Armadas 2, 18014 Granada, Spain.
Sci Total Environ. 2022 Oct 15;843:156965. doi: 10.1016/j.scitotenv.2022.156965. Epub 2022 Jun 25.
Bladder cancer (BC) is one of the top 10 most common tumours worldwide; however, no molecular markers are currently available for tumour management and follow-up. BC could benefit from molecular biomarkers in environmental disease, which provide mechanistic understanding of individual susceptibility to exposure-related cancers and allow characterizing genetic alterations in the molecular pathway for malignancy. This case-control study performed a molecular analysis in 99 BC and 125 controls. Buccal swabs were collected to assess SNPs in eleven genes coding for xenobiotic detoxification enzymes, cellular antioxidant defences, and hormone synthesis and signalling (NAT2 (rs1801280), GPX1 (rs1050450 and rs17650792), TXNRD1 (rs7310505), PRDX3 (rs3740562), PON1 (rs662), SOD1 (rs10432782), SOD2 (rs4880), CAT (rs1001179), CYP17A1 (rs743572) and ESR1 (rs746432)). A structured questionnaire was administered to study participants to assess environmental and dietary chemical exposures. Several miRNAs associated with BC and detoxification/antioxidant pathways were analysed in a subsample of the study population, including miR-93-5p, miR-221-3p, miR-126, miR-27a-3p, miR-193b, and miR-193a-5p. Levels of selected environmental pollutants (polycyclic aromatic hydrocarbons and endocrine disrupting chemicals) were determined in urine from a subsample of BC cases and controls. We found that CYP17A1, CAT, SOD1, ESR1, PON1, and GPX1 (rs17650792) were associated with BC risk. Furthermore, exposure to smoke and/or dust, and alcohol intake were identified as risk factors for BC. Increased urinary levels of benzo[a]pyrene and bisphenol A were observed in BC patients relative to controls, along with an increased expression of miR-193b, miR-27a and miR-93-5p in BC. Nevertheless, further studies with a larger sample size are warranted to confirm these exploratory results. This study also shows that the combination of genetic markers (PON1 and CYP17A1) and miRNA (miR-221-3p and miR-93-5p) open a new scenario in the use of non-invasive biomarkers in the stratification of BC to guide personalized medicine, which is extremely urged in the current clinical setting.
膀胱癌 (BC) 是全球十大最常见肿瘤之一；然而，目前尚无用于肿瘤管理和随访的分子标志物。BC 可以从环境疾病的分子生物标志物中受益，这些标志物提供了对个体易感性与暴露相关癌症的机制理解，并允许对恶性肿瘤分子途径中的遗传改变进行特征描述。这项病例对照研究对 99 例 BC 患者和 125 例对照者进行了分子分析。采集口腔拭子以评估编码外源性解毒酶、细胞抗氧化防御和激素合成及信号转导的 11 个基因中的 SNPs（NAT2(rs1801280)、GPX1(rs1050450 和 rs17650792)、TXNRD1(rs7310505)、PRDX3(rs3740562)、PON1(rs662)、SOD1(rs10432782)、SOD2(rs4880)、CAT(rs1001179)、CYP17A1(rs743572)和 ESR1(rs746432)）。研究参与者接受了一份结构化问卷，以评估环境和饮食化学暴露情况。在研究人群的一个亚样本中分析了与 BC 和解毒/抗氧化途径相关的几个 miRNA，包括 miR-93-5p、miR-221-3p、miR-126、miR-27a-3p、miR-193b 和 miR-193a-5p。在 BC 病例和对照者的尿液亚样本中测定了几种选定的环境污染物（多环芳烃和内分泌干扰化学物质）的水平。我们发现 CYP17A1、CAT、SOD1、ESR1、PON1 和 GPX1(rs17650792) 与 BC 风险相关。此外，发现暴露于烟雾和/或灰尘以及饮酒是 BC 的危险因素。与对照组相比，BC 患者的尿液中苯并[a]芘和双酚 A 的水平升高，同时 miR-193b、miR-27a 和 miR-93-5p 的表达增加。然而，需要更大样本量的进一步研究来证实这些探索性结果。这项研究还表明，遗传标记物（PON1 和 CYP17A1）和 miRNA（miR-221-3p 和 miR-93-5p）的组合为使用非侵入性生物标志物在 BC 分层中开辟了新的前景，以指导精准医学，这在当前临床环境中是极其迫切的。
