Serum level and single-nucleotide polymorphisms of toll-like receptor-7 among urinary bladder cancer Iraqi patients

Abstract

Background: 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. Results: 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). Conclusions: 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.

GENE EXPRESSION AND SINGLE NUCLEOTIDE POLYMORPHISM (rs1140713) OF MICRORNA-126

“…The interaction between sex hormones, the environment, and genotype during individual development, as well as the fact that all cases were adult, are the two most plausible explanations for the female predominance in SLE. This finding is consistent with earlier research that showed that females are more likely than males to develop SLE after puberty due to elevated levels of circulating oestrogen (4,29). The regulating role of microRNAs in the immune system occurs in a delicate tune.…”

“…Hardy-Weinberg equilibrium. Most studies agree that SLE affects women more frequently than it does men, and the findings from the studies given show a risk effect for female sex and age in the aetiology of SLE (33,28,4). The interaction between sex hormones, the environment, and genotype during individual development, as well as the fact that all cases were adult, are the two most plausible explanations for the female predominance in SLE.…”

Evaluation of Gene Expression Level of miRNA-29c, miRNA-125, miRNA-141, miRNA-145 and miRNA-205 as Predisposing Factors for Transitional Cell Carcinoma-Bladder Cancer in Iraqi Patients

“…An Iraqi study from Urology Clinic of Baghdad Teaching Hospital in 2019 included 66 patients with TCC with the age ranging 24-90 years. Male percentage was 89.4% 59 while for females it was 10.6% [18].…”

Assessment of miR-146a Gene Polymorphisms in Patients with Systemic Lupus Erythematosus

“…So the twentieth decade of age is considered a crucial risk factor for SLE exception before puberty age [22]. The female gender is an additional risk factor, and most studies agree that SLE occurs more frequently in women than in men [23][24][25]. Two important explanations may justify the female-gender dominancy in SLE; the interaction between the environment, genotype, and sex hormones during individual development, and all cases were adult and this is similar to previous research clarified, that females with SLE have a higher prevalence than males after puberty age due to high levels of circulating estrogen [25,26].…”