In thalassemia major or transfusion-dependent thalassemia patients, osteoporosis-related bone complications such as fracture events are common. However, no studies have investigated the risk of ...fracture in transfusion-naïve thalassemia population. Therefore, we conducted a longitudinal nationwide cohort study to determine whether this population has an increased risk of fracture. This nationwide, population-based cohort study analyzed data from 1998 to 2010 obtained from the Taiwanese National Health Insurance Research Database, with a follow-up period extending until the end of 2011. We identified cases with transfusion-naïve thalassemia and selected a comparison cohort that was frequency-matched according to age and year of diagnosis of thalassemia at a ratio of one subject with thalassemia to four subjects in the control group. We analyzed the risk of fracture events to occur in transfusion-naïve thalassemia cases by using Cox proportional hazards regression models. Totally, the study recruited 1369 transfusion-naïve thalassemia subjects and 5416 controls. We identified a total of 71 cases with fracture events within the thalassemia group and 204 within the control group. The overall risks for developing fracture events were 1.35-fold higher in transfusion-naïve thalassemia individuals than the comparison cohort after adjusting for age, sex and comorbidities. Most fracture events were observed in male transfusion-naïve thalassemia individuals rather than the normal population. In subgroup analysis, there was a 1.46-fold higher risk to develop upper-limb fracture in the thalassemia group than in the control groups. In conclusion, our long-term, cohort study results showed that there was a higher risk for the development of fractures in transfusion-naïve thalassemia individuals, particularly in male cases.
•In Transfusion-naïve thalassemia individuals, the risk of fractures was higher.•The risk for upper limb fractures was significantly higher.•The risk of fractures is 1.78 fold in male transfusion-naïve thalassemia cases.•Physicians should be aware of the possibility of fractures in this population.
Background/Aim: Evidence has shown that interleukin-18 (IL-18) has both antitumor and pro-tumor effects in various types of leukemia. The current study aimed at investigating the contribution of ...IL-18 polymorphisms to the risk of childhood acute lymphocytic leukemia (ALL) in Taiwan. Materials and Methods: IL-18 promoter −656 (rs1946519), −607 (rs1946518), and −137 (rs187238) genotypes of 266 childhood ALL cases and 266 controls were determined by polymerase chain reaction-restriction fragment length polymorphism methodology. Results: The distributions of genotypic and allelic frequencies of IL-18 rs1946519, rs1946518 or rs187238, were not significantly different between childhood ALL cases and controls (all p>0.05). However, in the stratification analysis among the cases, IL-18 rs187238 GC and CC genotypes were associated with increased childhood ALL risk and shorter survival (OR=4.19 and 2.93, 95%CI=2.04-8.64 and 1.19-7.23, p=0.0001 and 0.0250, respectively). No association was found with rs1946519 and rs1946518 (all p>0.05). Conclusion: IL-18 rs187238 GC and CC genotypes can serve as predictors for childhood ALL prognosis among Taiwanese. Validation in larger and various populations can greatly extend the feasibility of this novel predictor.
Sleep disorder (SD), especially sleep apnea, and its effect on atrial fibrillation (AF) are gathering attention. However, other SDs may also play an essential role in AF. The aim of the study is to ...investigate the effects of other SDs on the risk of atrial fibrillation development.
This study investigated the risk of AF in people diagnosed with SD compared with that in age and sex-matched unaffected individuals. This longitudinal, nationwide, population-based cohort study was conducted using data from the Taiwan National Health Insurance Research Database (NHIRD) of individuals diagnosed with SD from January 1, 2001, to December 31, 2012.
The sample consisted of 193,288 people with the SD, which include of 4406 people with sleep apnea, 73,704 people with insomnia, 107,395 people with sleep disturbance, 7,783 people with other SD, and 193,288 matched controls. A Cox proportional hazard regression was used to compute the risk of AF in people with SD and subgroup of SD, relative to that in people without SD. The AF incidences were 1.21-fold higher (95% CI 1.15–1.27) in the SD cohort, 1.19-fold higher (95% CI 0.91–1.56) in the sleep apnea cohort, 1.26-fold higher (95% CI 1.19–1.34) in the insomnia cohort, 1.15-fold higher (95% CI 1.08–1.22) in the sleep disturbance cohort, and 1.30-fold higher (95% CI 1.11–1.53) in other SDs, than in the control cohort, after age, sex, and comorbidities were adjusted.
This nationwide population-based cohort study indicates a strong relationship between SD and incident AF, and insomnia has a higher impact on AF compared with other SD.
•Risk of atrial fibrillation (AF) is associated with sleep disorders.•Insomnia potentially has highest impact on AF occurrence.•The risk of AF among insomnia patients is independent with ages and comorbidities.
There is still debate on whether high uric acid increases bone mineral density (BMD) against osteoporotic fracture or bone resorption caused by gout inflammation. This study aimed to evaluate whether ...gout offers a protective effect on bone health or not. We conducted a nationwide population-based retrospective cohort study to evaluate the association between gout history and risk factors of fracture.A retrospective cohort study was designed using the claim data from Longitudinal Health Insurance Database (LHID). A total of 43,647 subjects with gout and a cohort of 87,294 comparison subjects without gout were matched in terms of age and sex between 2001 and 2009, and the data were followed until December 31, 2011. The primary outcome of the study was the fracture incidence, and the impacts of gout on fracture risks were analyzed using the Cox proportional hazards model.After an 11-year follow-up period, 6992 and 11,412 incidents of fracture were reported in gout and comparison cohorts, respectively. The overall incidence rate of fracture in individuals with gout was nearly 23%, which was higher than that in individuals without gout (252 vs 205 per 10,000 person-years) at an adjusted hazard ratio of 1.17 (95% confidence interval = 1.14-1.21). Age, sex, and fracture-associated comorbidities were adjusted accordingly. As for fracture locations, patients with gout were found at significant higher fracture risks for upper/lower limbs and spine fractures. In gout patient, the user of allopurinol or benzbromarone has significantly lower risk of facture than nonusers.Gout history is considered as a risk factor for fractures, particularly in female individuals and fracture sites located at the spine or upper/lower limbs.
Chondrosarcoma, a common malignant tumour, develops in bone. Effective adjuvant therapy remains inadequate for treatment, meaning poor prognosis. It is imperative to explore novel remedies. ...Angiogenesis is a rate-limiting step in progression that explains neovessel formation for blood supply in the tumour microenvironment. Numerous studies indicate that EPCs (endothelial progenitor cells) promote angiogenesis and contribute to tumour growth. bFGF (basic fibroblast growth factor), a secreted cytokine, regulates biological activity, including angiogenesis, and correlates with tumorigenesis. However, the role of bFGF in angiogenesis-related tumour progression by recruiting EPCs in human chondrosarcoma is rarely discussed. In the present study, we found that bFGF induced VEGF (vascular endothelial growth factor) expression via the FGFR1 (fibroblast growth factor receptor 1)/c-Src/p38/NF-κB (nuclear factor κB) signalling pathway in chondrosarcoma cells, thereby triggering angiogenesis of endothelial progenitor cells. Our in vivo data revealed that tumour-secreted bFGF promotes angiogenesis in both mouse plug and chick CAM (chorioallantoic membrane) assays. Xenograft mouse model data, due to bFGF-regulated angiogenesis, showed the bFGF regulates angiogenesis-linked tumour growth. Finally, bFGF was highly expressed in chondrosarcoma patients compared with normal cartilage, positively correlating with VEGF expression and tumour stage. The present study reveals a novel therapeutic target for chondrosarcoma progression.
Tissue inhibitor of metalloproteinase-2 (TIMP-2) is an endogenous inhibitor of matrix metalloproteinase-2 and is highly expressed in breast cancer (BC) cases at diagnosis. However, the genetic ...investigations for the association of
genotypes with BC risk are rather limited. In this study, contribution of
rs8179090, rs4789936, rs2009196 and rs7342880 genotypes to BC risk was examined among Taiwan's BC population.
genotypic profiles were revealed among 1232 BC cases and 1232 controls about their contribution to BC using a PCR-based RFLP methodology. The
rs8179090 homozygous variant CC genotype was significantly higher in BC cases than controls (odds ratio (OR) = 2.76, 95% confidence interval (95%CI) = 1.78-4.28,
= 0.0001). Allelic analysis showed that C allele carriers have increased risk for BC (OR = 1.39, 95%CI = 1.20-1.62,
= 0.0001). Genotypic together with allelic analysis showed that
rs4789936, rs2009196 or rs7342880 were not associated with BC risk. Stratification analysis showed that
rs8179090 genotypes were significantly associated with BC risk among younger (≤55) aged women, not among those of an elder (>55) age. Last, rs8179090 genotypes were also associated with triple negative BC. This study sheds light into the etiology of BC in Taiwanese women. Rs8179090 may be incorporated into polygenic risk scores and risk prediction models, which could aid in stratifying individuals for targeted breast cancer screening.
Matrix metalloproteinase-9 (MMP-9) is responsible for modifying extracellular components and plays a crucial role in the metastatic behavior of cancer. This study aimed at examining the role of MMP-9 ...rs3918242 genotypes on colorectal cancer (CRC) risk.
A total of 362 CRC patients and 362 healthy subjects in Taiwan, were examined by the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) methodology.
The MMP-9 rs3918242 TT genotype carriers had a slightly increased risk of CRC compared to CC carriers (p=0.1642, OR=1.88, 95% CI=0.84-4.16). Patients of CT/TT genotypes were on significantly higher risk of metastasis (p=0.0027) than those of CC genotype. No obvious association was found between MMP-9 genotype and CRC risk among ever-smokers, non-smokers, non-alcohol drinkers or alcohol drinkers. No significant correlation was observed between MMP-9 genotypic distributions with age, gender, tumor size or location.
MMP-9 rs3918242 genotypes may interact with BMI to serve as a predictor for higher CRC risk, and independently as a predictor for metastasis.
Elevated serum interleukin-16 (IL-16) levels have been reported in gastric cancer (GC) tissues; however, the role of IL-16 genotypes in GC susceptibility remains largely unexplored. This study aimed ...to investigate the contribution of IL-16 genotypes to GC susceptibility and to assess their interactions with smoking, alcohol drinking, and Helicobacter pylori (H. pylori) infection.
Polymerase chain reaction-based restriction fragment length polymorphism (PCR-RFLP) methodology was employed to determine IL-16 rs4778889, rs11556218, and rs4072111 genotypic characteristics in 161 patients with GC and 483 controls.
Significant differences were observed in the distribution of genotypic (p=0.0009) and allelic (p=0.0002) frequencies of IL-16 rs11556218 among cases and controls. Specifically, the frequencies of TG and GG genotypes of IL-16 rs11556218 were 37.3% and 6.8% among patients with GC, respectively, which were higher than those among the controls (26.7% and 2.7%). In contrast, no significant differences were found concerning IL-16 rs4778889 or rs4072111. Notably, individuals with IL-16 rs11556218 TT genotypes exhibited significant protective effects against GC when exposed to risk factors, such as smoking, alcohol drinking, and H. pylori infection.
IL-16 rs11556218 T allele was associated with reduced susceptibility to GC. Furthermore, carriers of the TT genotype showed protection against GC risk factors, including smoking, alcohol drinking, and H. pylori infection. These findings provide valuable insights into the potential role of IL-16 genotypes in GC development and their interactions with lifestyle and infectious factors.
Background/Aim: A single study has shown positive association and genotype-phenotype correlation between metalloproteinase-9 (MMP-9) promoter genotypes and adult acute lymphocytic leukemia (ALL). ...However, there is no report about childhood ALL. Thus, this study aimed at examining the role of MMP-9 rs3918242 genotypes in childhood ALL risk. Patients and Methods: A total of 266 childhood ALL cases and 266 healthy controls in Taiwan were examined for their MMP-9 rs3918242 genotypes via polymerase chain reaction-restriction fragment length polymorphism methodology. Results: The MMP-9 rs3918242 CT or TT genotype carriers only had a slightly increased risk compared with CC carriers (p=0.6386 and 0.6005, respectively). The allelic frequency analysis also supported the idea that the variant T allele at MMP-9 rs3918242 is not differentially distributed between the case and control groups (p=0.4834). Conclusion: MMP-9 rs3918242 genotypes may indirectly influence the risk of childhood ALL. Further validations in other populations and analysis of the detail mechanisms are needed.
Chondrosarcomas are primary malignant bone tumors that have a poor prognosis. WNT1-inducible signaling pathway protein-3 (WISP-3, also termed CCN6) belongs to the CCN family of proteins and is ...implicated in the regulation of various cellular functions, such as cell proliferation, differentiation, and migration. It is unknown as to whether CCN6 affects human chondrosarcoma metastasis. We show how CCN6 promotes chondrosarcoma cell migration and invasion via matrix metallopeptidase-9 (MMP)-9 expression. These effects were abolished by pretreatment of chondrosarcoma cells with PI3K, Akt, mTOR, and NF-κB inhibitors or short interfering (si)RNAs. Our investigations indicate that CCN6 facilitates metastasis through the PI3K/Akt/mTOR/NF-κB signaling pathway. CCN6 and MMP-9 expression was markedly increased in the highly migratory JJ012(S10) cell line compared with the primordial cell line (JJ012) in both in vitro and in vivo experiments. CCN6 knockdown suppressed MMP-9 production in JJ012(S10) cells and attenuated cell migration and invasion ability. Importantly, CCN6 knockdown profoundly inhibited chondrosarcoma cell metastasis to lung. Our findings reveal an important mechanism underlying CCN6-induced metastasis and they highlight the clinical significance between CCN6 and MMP-9 in regard to human chondrosarcoma. CCN6 appears to be a promising therapeutic target in chondrosarcoma metastasis.
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