Toll-like receptor 7 (TLR7), a member of TLR family, plays a pivotal role in pathogenesis of different malignancies. Among these is urinary bladder cancer (UBC), which has not been extensively studied. Therefore, it was aimed to determine TLR7 serum level in UBC patients and evaluate its association with some demographic and clinicopathological characteristics. In addition, four TLR7 single-nucleotide polymorphisms (SNPs: rs179018, rs179019, rs179020, and rs179021) were investigated to determine their susceptibility role in UBC and inspect SNP’s impact on TLR7 level. Sixty-six UBC Iraqi patients were enrolled in this case-control study. Two control samples were also involved, 40 urinary tract infection (UTI) patients, and 48 healthy control subjects. Male gender, older age, and cigarette-smoking are risk factors for UBC. TLR7 level showed a significant decreased median in UBC patients compared to UTI patients or control (1.4 vs. 8.1 and 9.5 ng/ml, respectively; p < 0.001). The decrease was more pronounced in males, age group ≥ 48 years, cigarette-smokers, alcohol non-consumers, clinical stages I–II, and superficial tumor, as well as patients with family history of cancer and untreated patients. Mitomycin C and Bacillus Calmette–Guérin therapies tended to increase TLR7 level. Among the four investigated SNPs, only rs179019 C allele showed significantly uncorrected increased frequency in UBC males compared to control males (p = 0.038), while among UTI females, C allele frequency maintained a significantly corrected decreased frequency compared to control females (p = 0.005). Some SNPs influenced serum level of TLR7, but a significant impact was recorded for rs179019 in UTI females (p = 0.006). Downregulation of TLR7 is suggested to have a role in etiology and pathogenesis of UBC, especially the male, elderly and smoker patients. Mitomycin C and Bacillus Calmette–Guérin may enhance TLR7 production in the blood of UBC patients. TLR7 SNPs are suggested to influence susceptibility to develop UBC, and their potential in impacting TLR7 serum level is augmented.

中文翻译：

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伊拉克膀胱癌患者血清toll样受体7的水平及单核苷酸多态性

Toll 样受体 7 (TLR7) 是 TLR 家族的成员，在不同恶性肿瘤的发病机制中起关键作用。其中包括尚未得到广泛研究的膀胱癌 (UBC)。因此，旨在确定 UBC 患者的 TLR7 血清水平并评估其与一些人口统计学和临床​​病理学特征的关联。此外，研究了四个 TLR7 单核苷酸多态性（SNP：rs179018、rs179019、rs179020 和 rs179021）以确定它们在 UBC 中的易感性作用并检查 SNP 对 TLR7 水平的影响。66 名 UBC 伊拉克患者参加了这项病例对照研究。还涉及两个对照样本，40 名尿路感染 (UTI) 患者和 48 名健康对照受试者。男性、年龄较大和吸烟是 UBC 的危险因素。与 UTI 患者或对照组相比，UBC 患者的 TLR7 水平显着降低（分别为 1.4 与 8.1 和 9.5 ng/ml；p < 0.001）。在男性、年龄组≥ 48 岁、吸烟者、不饮酒者、临床 I-II 期和浅表肿瘤，以及有癌症家族史的患者和未经治疗的患者中，这种下降更为明显。丝裂霉素 C 和卡介苗-Guérin 疗法倾向于增加 TLR7 水平。在四个研究的 SNP 中，只有 rs179019 C 等位基因在 UBC 男性中显示出与对照男性相比显着未校正的频率增加（p = 0.038），而在 UTI 女性中，与对照女性相比，C 等位基因频率保持了显着校正的降低频率（p = 0.005 ）。一些 SNP 影响 TLR7 的血清水平，但在 UTI 女性中记录了 rs179019 的显着影响（p = 0.006）。TLR7 的下调被认为在 UBC 的病因和发病机制中起作用，尤其是男性、老年和吸烟患者。丝裂霉素 C 和卡介苗芽孢杆菌可能会增加 UBC 患者血液中 TLR7 的产生。建议 TLR7 SNP 影响发展 UBC 的易感性，并且它们影响 TLR7 血清水平的潜力得到增强。