The clinical use of Skype—For which patients, with which problems and in which settings? A snapshot review of the literature

DNA double-strand breaks (DSBs) are deleterious DNA lesions that if left unrepaired or are misrepaired, potentially result in chromosomal aberrations, known drivers of carcinogenesis. Pathways that direct the repair of DSBs are traditionally believed to be guardians of the genome as they protect cells from genomic instability. The prominent DSB repair pathway in human cells is the non-homologous end joining (NHEJ) pathway, which mediates template-independent re-ligation of the broken DNA molecule and is active in all phases of the cell cycle. Its role as a guardian of the genome is supported by the fact that defects in NHEJ lead to increased sensitivity to agents that induce DSBs and an increased frequency of chromosomal aberrations. Conversely, evidence from tumors and tumor cell lines has emerged that NHEJ also promotes chromosomal aberrations and genomic instability, particularly in cells that have a defect in one of the other DSB repair pathways. Collectively, the data present a conundrum: how can a single pathway both suppress and promote carcinogenesis? In this review, we will examine NHEJ’s role as both a guardian and a disruptor of the genome and explain how underlying genetic context not only dictates whether NHEJ promotes or suppresses carcinogenesis, but also how it alters the response of tumors to conventional therapeutics.

https://www.mdpi.com/2072-6694/9/7/81/pdf

The Role of the Core Non-Homologous End Joining Factors in Carcinogenesis and Cancer

Lung cancer is both the most common diagnosed cancer and the leading cause of cancer related deaths in China. During the past three decades, the incidence and mortality of lung cancer in China are increasing rapidly. According to data from National Central Cancer Registry (NCCR) in 2010, the crude incidence of lung cancer in China was 46.08 per 100,000 population (61.86 per 100,000 men and 29.54 per 100,000 women), with an estimated over 600,000 new diagnosed lung cancer patients (416,333 males and 189,613 females). Meanwhile, the crude mortality of lung cancer in China was 37.00 per 100,000 population (50.04 per 100,000 men and 23.33 per 100,000 women). Consistent with the change in developed countries, adenocarcinoma has become the most predominant histological subtype of lung cancer in China. For the majority advanced non-small-cell lung cancer (NSCLC) patients, especially patients with adenocarcinoma, targeted therapy became increasing important in the treatment. Chinese researcher have done a lot work in terms of lung cancer molecular epidemiology, therefore, in this review, we further summarized the epidemiology of driver genes in NSCLC, hoping to help clinicians to better screen certain driver genes in China for treatment decisions.

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Lung cancer molecular epidemiology in China: recent trends.

OBJECTIVE To estimate the cost of kidney stone disease (KSD) in England. PATIENTS AND METHODS We conducted a retrospective cohort study of patients with KSD, referred to a metabolic stone clinic between 1990 and 2007 using electronic records of patients with KSD in a tertiary referral centre, to determine cost using UK National Health Service (NHS) tariff, with subsequent extrapolation to the entire England population. Those with no documentation and <5 years follow-up were excluded. The outcome measure was calculation of cost (as per 2018 NHS tariff) presented as lower and higher estimates for: per episode; total within the cohort; and estimation of initial, 5-,10- and 15-year costs for the cohort and total population in England. Linear regression was used to examine for significant predictors of per episode and total cost. RESULTS A total of 781 patients were included in the study after 1000 records were screened for inclusion, with a mean follow-up of 19 years. The mean (SD) overall costs per episode were between £1277 (1724) and £2887 (2492). Total initial costs for the cohort were between £950 842 and £2 336 442, rising to between £1.43 million and £3.02 million at 15 years of follow-up. Estimated cost in 2010 in England alone was between £190 million and £324 million. CONCLUSION KSD is a costly disease, comparable to the combined cost of prostate and bladder cancer in UK.

Evaluation of the Economic Burden of Kidney Stone Disease in the UK: A Retrospective Cohort study with a mean follow‐up of 19 years

Urothelial carcinoma (UC) arises extensively from the renal pelvis, ureter, urinary bladder, and urethra. UC represents a clinical and social challenge because of its incidence, post-treatment recurrence rate, and prognosis. Combinations of urine cytology, cystoscopy, and conventional imaging such as computed tomography are currently used for diagnosis and monitoring modalities of UC. Both the poor diagnostic accuracy of urine cytology and poor cost performance of cystoscopy and conventional imaging modalities emphasize the urgent need for advancement in clinical guidance for UC. Urine- and blood-based biomarkers for detection of UC of the bladder and upper urinary tract represent a considerable research area. Biomarkers can help to improve UC diagnosis with the aim of replacing cystoscopy and other imaging examinations in future and may enable individualizing risk stratification regarding therapy and follow-up. Over the decades, numerous studies have focused on the potential application of biomarkers for UC, including urine, circulating tumor DNA, RNAs, proteins, and extracellular vesicles. Although some biomarkers such as ImmunoCyt/uCyt+, UroVysion, NMP-22, bladder tumor antigen, CxBladder, and Xpert Bladder Cancer are currently available in clinical practice, few biomarkers achieve high sensitivity and specificity. Emerging biomarkers are continuously developed and reported in medical journals. However, there is a significant lack on following external validation using different cohorts. The positive results are needed to be confirmed by more studies with large-scale cohorts and long follow-up periods to prove the true value of novel biomarkers, followed by their adoption in clinical practice. The present paper provides an overview of the evidence based on high-impact studies regarding urine- and blood-based biomarkers and their clinical applications in bladder cancer and upper tract UC.

/pdf/emerging-biomarkers-for-the-diagnosis-and-monitoring-of-2k5tklvyqk.pdf

Emerging biomarkers for the diagnosis and monitoring of urothelial carcinoma.

Objectives

To investigate whether patients with urolithiasis are at an increased risk of anxiety and depression.



Methods

We used universal insurance claims data in Taiwan from 2000 to 2011 to identify patients with newly diagnosed urolithiasis (n = 32 617) and those without urolithiasis (n = 130 465). Incidences, hazard ratios, and incidence rate ratios of anxiety and depression were determined in both cohorts in terms of baseline demographic characteristics and comorbidities until December 2011.



Results

The urolithiasis cohort yielded a higher incidence of anxiety (11.9 vs 6.91 per 1000 person-years) with an adjusted hazard ratio of 1.5 (95% confidence interval 1.42–1.57) than the non-urolithiasis cohort. The urolithiasis cohort also showed a higher incidence of depression (5.79 vs 3.95 per 1000 person-years) with an adjusted hazard ratio of 1.26 (95% confidence interval 1.18–1.35) than the non-urolithiasis cohort. Regardless of the patients' baseline comorbidities, patients with urolithiasis showed a higher incidence rate ratio of anxiety and depression than those without urolithiasis (with no comorbidities: adjusted hazard ratio 1.62, 95% confidence interval 1.49–1.76] for anxiety and adjusted hazard ratio 1.37, 95% confidence interval 1.23–1.54 for depression).



Conclusion

Urolithiasis is recurrent, and significantly associated with anxiety and depression. Therefore, urologists should diagnose patients suspected with this disease and provide proper medical care.

Increased risk of anxiety among patients with urolithiasis: A nationwide population-based cohort study.

Background: The DNA non-homologous end- joining repair gene XRCC6 (Ku70) plays a key role in both the DNA double-strand break (DSB) repair and cell cycle arrest. Defects in DSB repair capacity can lead to genomic instability. We hypothesized that a variant in the XRCC6 gene was associated with susceptibility to renal cell carcinoma (RCC). Materials and Methods: In a hospital- based case-control study of 92 patients with RCC and 580 cancer-free controls, the frequency matched by age and sex, the associations of XRCC6 promoter T-991C (rs5751129), promoter G-57C (rs2267437), promoter A-31G (rs132770), and intron 3 (rs132774) polymorphisms with RCC risk were investigated in a Taiwanese population. At the same time, 30 adjacent renal tissue samples were tested to estimate the XRCC6 mRNA expression by real-time quantitative reverse transcription. Results: Compared with the TT genotype, the TC genotype had a significantly increased risk of RCC (adjusted odds ratio=2.24, 95% confidence interval=1.25- 4.08, p=0.0175). The in vivo mRNA expression in renal tissues revealed a statistically significant lower XRCC6 mRNA expression in samples with TC/CC genotypes compared to those with the TT genotype (p=0.0039). Conclusion: These evidence suggests that the XRCC6 T-991C genotype together with its mRNA expression are involved in the etiology of RCC and may be a marker for susceptibility to RCC in the population of Taiwan. Renal cell carcinoma (RCC) is the predominant form of malignancy of the kidney (>80%), and its frequency is increasing in both men and women. RCC occurs worldwide,

The Role of XRCC6 T-991C Functional Polymorphism in Renal Cell Carcinoma

Aim The DNA repair gene X-ray repair complementing defective repair in Chinese hamster cells 6 (XRCC6) is thought to play an important role in the repair of DNA double-strand breaks. It is known that defects in double-strand break repair capacity can lead to irreversible genomic instability. However, the association of polymorphic variants of XRCC6 with lung cancer susceptibility has never been reported. In this hospital-based case-control study, the association of XRCC6 promoter T-991C (rs5751129), promoter G-57C (rs2267437), promoter G-31A (rs132770), and intron 3 (rs132774) polymorphisms with lung cancer risk in a Taiwanese population, was studied. Materials and methods In total, 358 patients with lung cancer and 716 healthy controls recruited from the China Medical Hospital in Taiwan were genotyped. Results The results showed that there were significant differences between lung cancer and control groups in the distribution of their genotypic (p=3.7×10(-4)) and allelic frequency (p=2.7×10(-5)) in the XRCC6 promoter T-991C polymorphism. Individuals who carried at least one C allele (TC or CC) had a 2.03-fold increased odds ratio of developing lung cancer compared to those who carried the wild-type TT genotype (95% conference internal=1.42-2.91, p=0.0001). For the other three polymorphisms, there was no difference between the case and control groups in the distribution of either genotypic or allelic frequency. Conclusion In conclusion, the XRCC6 promoter T-991C, but not the promoter C-57G, promoter G-31A or intron 3, is associated with lung cancer susceptibility.

Association of DNA double-strand break gene XRCC6 genotypes and lung cancer in Taiwan

AIM Bladder cancer is the sixth most common cancer worldwide and its incidence is particularly high in southwestern Taiwan. However, the genetic contribution to its etiology is not well-understood. The aim of this study is to evaluate the association of cyclooxygenase 2 (Cox-2) polymorphic genotypes with Taiwan bladder cancer patients. MATERIALS AND METHODS Six polymorphic variants of Cox-2 were analyzed regarding their association with bladder cancer risk, and three hundred and seventy-five patients with bladder cancer and same amount of age- and gender-matched healthy controls recruited were genotyped by the PCR-RFLP method. RESULTS Among the six polymorphic sites examined, only the Cox-2 promoter G-765C (rs20417) genotypes were positively associated with bladder cancer risk (p=0.0102). Individuals with the Cox-2 -765GC genotypes were associated with higher prostate cancer risk than those with -765GG. CONCLUSION Our findings provide evidence that the C allele of Cox-2 promoter G-765C may be associated with the overexpression of COX-2 during bladder cancer development and may be a useful marker for the early detection of bladder cancer.

Associations of cyclooxygenase 2 polymorphic genotypes with bladder cancer risk in Taiwan.

AIM Upper urothelial tract cancer is unusually of high incidence in Taiwan and it is valuable to study the specificity of this disease in Taiwan and compare the corresponding findings with those of Western countries. In the literature, it has been reported that single nucleotide variation of caveolin-1 gene (CAV1) plays an important role in risk of several types of cancer, such as hepatoma, leukemia, nasopharyngeal carcinoma, oral, breast, bladder and prostate cancer, but we are not aware of any reports on upper urothelial tract cancer. The aim of this study was to evaluate the association of six polymorphic genotypes of CAV1 with upper urothelial tract cancer within a Taiwanese population. MATERIALS AND METHODS A total of 218 patients with upper urothelial tract cancer and 580 healthy controls in central Taiwan were genotyped by polymerase chain reaction and restriction fragment length polymorphism (PCR-RFLP) for six CAV1 polymorphic genotypes, C521A (rs1997623), G14713A (rs3807987), G21985A (rs12672038), T28608A (rs3757733), T29107A (rs7804372), and G32124A (rs3807992), and their association with upper urothelial tract cancer susceptibility was examined. RESULTS The distribution of genotypes of CAV1 rs3807987 and rs7804372 were significantly different between cancer patient and control groups (p=0.0188 and 0.0090, respectively), while those for CAV1 rs1997623, rs12672038, rs3757733 and rs3807992 were not significant (p>0.05). The haplotype analysis of the two polymorphic genotypes showed that compared with the GG/AT, and GG/AA haplotypes of CAV1 rs3807987/rs7804372, those carrying GG/TT, AG/TT and AA/TT variants have a significantly increased risk of upper urothelial tract cancer (odds ratio=1.61, 1.50 and 2.67, 95% confidence interval=1.05-2.47, 1.18-1.90, and 1.37-5.18, respectively). On the contrary, other haplotype variants conferred non-significant elevated risk. CONCLUSION Our results suggest that individual and combined CAV1 rs3807987/rs7804372 genotypes are involved in predisposition to upper urothelial tract cancer in the Taiwanese population.

Chi-Shun Lien

Papers

Increased risk of anxiety among patients with urolithiasis: A nationwide population-based cohort study.

The Role of XRCC6 T-991C Functional Polymorphism in Renal Cell Carcinoma

Association of DNA double-strand break gene XRCC6 genotypes and lung cancer in Taiwan

Associations of cyclooxygenase 2 polymorphic genotypes with bladder cancer risk in Taiwan.

Significant Association of Caveolin-1 (CAV1) Genotypes with Upper Urothelial Tract Cancer