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Jen-Sheng Pei,1,* Wen-Shin Chang,2,* Pei-Chen Hsu,1,* Chao-Chun Chen,1 Shun-Ping Cheng,3 Yun-Chi Wang,2 Chia-Wen Tsai,2,* Te-Chun Shen,2,4,* Da-Tian Bau2,5,6,* 1Department of Pediatrics, Taoyuan General Hospital, Ministry of Health and Welfare, Taoyuan, Taiwan, Republic of China; 2Terry Fox Cancer Research Laboratory, Translational Medicine Research Center, China Medical University Hospital, Taichung, Taiwan, Republic of China; 3Department of Physical Medicine and Rehabilitation, Taoyuan General Hospital, Ministry of Health and Welfare, Taoyuan, Taiwan, Republic of China; 4Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, China Medical University Hospital, Taichung, Taiwan, Republic of China; 5Graduate Institute of Biomedical Sciences, China Medical University, Taichung, Taiwan, Republic of China; 6Department of Bioinformatics and Medical Engineering, Asia University, Taichung, Taiwan, Republic of China *These authors contributed equally to this work Purpose: A growing body of evidence shows an association between DNA repair protein genotypes and susceptibility to various cancers. However, few studies have assessed the contribution of the genotype of XRCC3, a homologous repair gene, to the occurrence or prognosis of childhood acute lymphoblastic leukemia (ALL). In this study, we investigated the contribution of seven XRCC3 polymorphisms to childhood ALL.Patients and methods: We recruited 266 patients with childhood ALL and 266 healthy controls. Genomic DNA was isolated from peripheral blood samples. The XRCC3 rs1799794, rs45603942, rs1799796, rs861530, rs28903081, rs861539, and rs3212057 polymorphic genotypes of each subject were determined through conventional polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) analysis.Results: Genotypes with the rs861539 polymorphism were significantly associated with the risk of childhood ALL. The allelic distribution analyses suggested a significant association between the T allele at rs861539 with an increased risk of childhood ALL in the Taiwanese population. Polymorphic variants of XRCC3 at rs3212057 or rs28903081 did not exist in the study population. XRCC3 rs1799794, rs45603942, rs1799796, and rs861530 were not significantly associated with the risk of childhood ALL in the Taiwanese population.Conclusion: Our findings suggest that XRCC3 genotypes with polymorphisms at rs861539 may play a role in determining individual susceptibility to childhood ALL in this Taiwanese population. The polymorphism may be a potential detector and predictor of childhood ALL. Keywords: acute lymphoblastic leukemia, ALL, childhood, genotype XRCC3, polymorphism, Taiwan

Chung-Yu Huang,1,2 Wen-Shin Chang,3 Chia-Wen Tsai,3 Te-Chun Hsia,3 Te-Chun Shen,3,* Da-Tian Bau,3–5,* Hao-Ai Shui1,* 1Graduate Institute of Medical Sciences, National Defense Medical Center, Taipei, Taiwan; 2Taoyuan Armed Forces General Hospital, Taoyuan, Taiwan; 3Terry Fox Cancer Research Laboratory, Translational Medicine Research Center, China Medical University Hospital, Taichung, Taiwan; 4Graduate Institute of Biomedical Sciences, China Medical University, Taichung, Taiwan; 5Department of Bioinformatics and Medical Engineering, Asia University, Taichung, Taiwan *These authors contributed equally to this work Background: The incidence rate of nasopharyngeal carcinoma (NPC) has been documented to be high in Southeast Asia. Interleukin-18 (IL-18) is a multifunctional cytokine that augments interferon-γ production and acts as an important immunomediator in the development of several types of cancer.Patients and methods: This case–control study evaluated the role of IL-18 in NPC at the DNA level by genotyping its promoter polymorphisms at positions -656, -607, and -137 in a Taiwanese population. A total of 176 patients with NPC and age- and gender-matched 352 noncancer controls were included in this study.Results: The CC genotype of the IL-18-607 polymorphism was found to be associated with significantly decreased risks of NPC compared to the AA genotype (crude OR =0.50, 95% CI =0.29–0.84, P=0.0093). This significant difference persisted even in the dominant and recessive models. A significantly lower C allele frequency at position -607 was detected in the NPC group (41.8% vs 50.3%; OR =0.77; 95% CI =0.63–1.04, P=0.0089). Regarding IL-18-656 and -137 polymorphisms, there were no differential distributions of their genotypes between the NPC and control groups. After substratification of the subjects according to their smoking, alcohol consumption, and areca chewing status, the genotype distribution of the IL-18-607 polymorphism was found to be different only among nonsmokers between the NPC and control subgroups.Conclusion: This study suggests that IL-18 plays an important role in the carcinogenesis of NPC in Taiwan and that the genotype–phenotype correlation of IL-18-607 polymorphism and its contribution to NPC need to be investigated further. Keywords: genotype, IL-18, nasopharyngeal carcinoma (NPC), polymorphism, Taiwan

Background/aim: The dysregulation of matrix metalloproteinase (MMP) proteins has been reported to be involved in the etiology of pterygium. However, studies about the role of matrix metalloproteinase-11 (MMP-11) are lacking. This study is the first to examine the genomic role of MMP-11 in pterygium., Materials and Methods: The genotypes of MMP-11 rs738791, rs2267029, rs738792, and rs28382575 were determined in 140 pterygium cases and 280 non-pterygium controls by utilizing polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) and direct sequencing., Results: The genotypic frequencies of MMP-11 rs738792 TT, CT and CC were 40.0%, 50.7%, and 9.3% in the pterygium group, significantly different from those in the non-pterygium group (55.0%, 37.1%, and 7.9%, respectively; p for trend=0.0139). Specifically, individuals carrying the variants CT and CC had a 1.88- and 1.63-fold odds ratio of pterygium risk [95% confidence interval (CI)=1.22-2.89 and 0.77-3.44, p=0.0054 and 0.2834, respectively]. In the dominant model, individuals carrying CT+CC had significantly higher pterygium risk (odds ratio=1.83, 95%CI=1.21-2.77, p=0.0052). No association was found for other MMP-11 polymorphisms. Allelic analysis showed that MMP-11 rs738792 C allele was significantly associated with pterygium risk (odds ratio=1.48, 95%CI=1.08-2.01, p=0.0169). for the variant alleles of other MMP-11 polymorphisms were not associated with pterygium risk., Conclusion: The MMP-11 rs738792 genotypes can serve as a predictive marker for pterygium risk in Taiwanese. Additionally, elucidating the role of MMP-11 in the pathogenesis of pterygium could inform targeted therapies based on MMP-11 modulation., (Copyright © 2024 International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Background/aim: In gastric cancer (GCa) tissues, the mRNA and protein levels of tissue inhibitor of metalloproteinase-1 (TIMP-1) are significantly elevated compared to adjacent non-cancerous tissues. Moreover, the abnormal up-regulation of TIMP-1 has been associated with a poor prognosis. However, the role of TIMP-1 genotypes in susceptibility to GCa has seldom been investigated. This study aimed to evaluate the influence of TIMP-1 genotypes on GCa susceptibility and their potential interactions with clinico-pathological factors, including age, sex, body mass index, smoking, alcohol consumption, Helicobacter pylori (H. pylori) infection, and metastasis status., Materials and Methods: TIMP-1 rs4898, rs6609533, and rs2070584 genotypes were analyzed in 161 patients with GCa and 483 non-cancer control subjects from a Taiwanese population using PCR-RFLP methodology and direct sequencing., Results: The genotypic (p for trend=0.1987) and allelic (p=0.0733) frequencies of TIMP-1 rs4898 did not differ significantly between GCa cases and controls. Under the dominant model, combined CT+CC genotypes were not associated with GCa risk [odds ratio (OR)=0.74, 95% confidence interval (95%CI)=0.51-1.07, p=0.1272]. Similarly, no significant association was found for TIMP-1 rs6609533 or rs2070584 polymorphisms. Importantly, patients with GCa carrying the TIMP-1 rs4898 TT genotype exhibited a significantly enhanced risk of GCa when they had smoking (p=0.0140) and alcohol drinking habits (p=0.0011). Furthermore, the CC genotype of TIMP-1 rs4898 was linked to a lower risk of distant metastasis., Conclusion: The TIMP-1 rs4898 CC genotype may serve as a prognostic biomarker and could inform lifestyle modifications aimed at GCa prevention. Validation of TIMP-1 genotypic profile in diverse populations is warranted., (Copyright © 2024 International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Background/aim: The administration of contrast agents can adversely affect kidney function. Nevertheless, the nephrotoxicity of iopromide in human renal cells, potential therapeutic agents, and the underlying molecular mechanisms have not been thoroughly investigated., Materials and Methods: The proliferation of HEK-293 kidney cells was assessed using the 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazoliumbromide (MTT) assay. Apoptotic cell death was examined using the TUNEL assay and caspase-3 activity measurements. The impacts and potential pathways of epigallocatechin-3-gallate (EGCG) on iopromide-induced renal damage were analyzed through whole transcriptome sequencing. The redox state was assessed by measuring reactive oxygen species (ROS) production and 2,2-Diphenyl-1-picrylhydrazyl (DPPH) radical scavenging activity., Results: Iopromide-induced inhibition of cell proliferation and apoptosis in HEK-293 cells was counteracted by EGCG co-treatment. Pathway analysis revealed that molecules related to antioxidant and anti-inflammatory responses, such as ERK1/2, STAT1, and NF-[Formula: see text]B, were pivotal in the action of EGCG., Conclusion: Iopromide-induced ROS production, decreased DPPH scavenging ability, DNA strand breaks, elevated caspase-3 activity, and reduced cell proliferation were all reversed by EGCG co-treatment in HEK-293 cells. The mechanisms likely involve the attenuation of oxidative stress, inflammatory responses, and apoptosis, with regulation through the ERK1/2, STAT1, and NF-[Formula: see text]B pathways. Further research is necessary to confirm the protective effects of EGCG on renal function, particularly against damage induced by contrast agents like iopromide., (Copyright © 2024, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Naringin, a bioflavonoid compound from grapefruit or citrus, exerts anticancer activities on cervical, thyroid, colon, brain, liver, lung, thyroid, and breast cancers. The present investigation addressed exploring the anticancer effects of naringin on nasopharyngeal carcinoma (NPC) cells. Naringin exhibits a cytotoxic effect on NPC-TW 039 and NPC-TW 076 cells with IC 50 372/328 and 394/307 μM for 24 or 48 h, respectively, while causing little toxicity toward normal gingival epithelial (SG) cells (>500/500 μM). We established that naringin triggered G 1 arrest is achieved by suppressing cyclin D1, cyclin A, and CDK2, and upregulating p21 protein in NPC cells. Exposure of NPC cells to naringin caused a series of events leading to apoptosis including morphology change (cell shrinkage and membrane blebbing) and chromatin condensation. Annexin V and PI staining indicated that naringin treatment promotes necrosis and late apoptosis in NPC cells. DiOC 6 staining showed a decline in the mitochondrial membrane potential by naringin treatment, which was followed with cytochrome c release, Apaf-1/caspase-9/-3 activation, PARP cleavage, and EndoG expression in NPC cells. Naringin upregulated proapoptotic Bax and decreased antiapoptotic Bcl-xL expression, and dysregulated Bax/Bcl-xL ratio in NPC cells. Notably, naringin enhanced death receptor-related t-Bid expression. Furthermore, an increased Ca 2+ release by naringin treatment which instigated endoplasmic reticulum stress-associated apoptosis through increased IRE1, ATF-6, GRP78, GADD153, and caspase-12 expression in NPC cells. In addition, naringin triggers ROS production, and inhibition of naringin-induced ROS generation by antioxidant N-acetylcysteine resulted in the prevention of G 1 arrest and apoptosis in NPC cells. Naringin-induced ROS-mediated G 1 arrest and mitochondrial-, death receptor-, and endoplasmic reticulum stress-mediated apoptosis may be a promising strategy for treating NPC., (© 2024 Wiley Periodicals LLC.)

We conducted the first genome-wide association study (GWAS) of colorectal cancer (CRC) in Taiwan with 5342 cases and 61,015 controls. Ninety-two SNPs in three genomic regions reached genome-wide significance (p < 5 × 10 -8 ). The lead SNPs in these three regions were: rs12778523 (OR = 1.18, 95% CI, 1.15-1.23, p = 4.51 × 10 -13 ), an intergenic SNP between RNA5SP299 and LINC02676 at chromosome 10p14; rs647161 (OR = 1.14, 95% CI, 1.09-1.19, p = 2.21 × 10 -9 ), an intronic SNP in PITX1 at 5q31.1, and rs10427139 (OR = 1.20, 95% CI, 1.14-1.28, p = 3.62 × 10 -9 ), an intronic SNP in GPATCH1 at 19q13.1. We further validated CRC susceptibility SNPs previously identified through GWAS in other populations. A total of 61 CRC susceptibility SNPs were confirmed in Taiwanese. The top validated putative CRC susceptibility genes included: POU2AF2, HAO1, LAMC1, EIF3H, BMP2, ZMIZ1, BMP4, POLD3, CDKN1A, PREX1, CDKN2B, CDH1, and LRIG1. The top enriched pathways included TGF-β signaling, BMP signaling, extracellular matrix organization, DNA repair, and cell cycle control. We could not validate SNPs in HLA-G at 6p22.1 and in NOTCH4 at 6p21.32. We generated a weighted genetic risk score (GRS) using the 61 SNPs and constructed receiver operating characteristic (ROC) curves using the GRS to predict CRC. The area under the ROC curve (AUC) was 0.589 for GRS alone and 0.645 for GRS, sex, and age. These susceptibility SNPs and genes provide important insights into the molecular mechanisms of CRC development and help identify high-risk individuals for CRC in Taiwan., (© 2024 Wiley Periodicals LLC.)

Background/aim: In gastric cancer (GCa) tissues, mRNA expression of matrix metalloproteinase-8 (MMP-8) is notably reduced compared to healthy tissues. Furthermore, abnormally low or elevated serum levels of MMP-8 have been linked to a significantly poor prognosis. The involvement of MMP-8 genotypes in susceptibility to GCa remains underexplored. We aimed to assess the influence of MMP-8 genotypes on GCa susceptibility and their potential interactions with smoking, alcohol consumption, and Helicobacter pylori (H. pylori) infection., Patients and Methods: The study utilized polymerase chain reaction-based restriction fragment length polymorphism (PCR-RFLP) to analyze MMP-8 rs11225395, rs34009635, and rs35866072 genotypes in 161 GCa patients and 483 controls., Results: No statistically significant difference was detected in the distribution of genotypic (p for trend=0.3635) or allelic (p=0.1954) frequencies of MMP-8 rs11225395. Under a dominant model, combined CT+TT genotypes showed no association with GCa risk [odds ratio (OR)=0.77, 95% confidence interval (95%CI)=0.54-1.10, p=0.1852]. Similarly, no association was observed for MMP-8 rs34009635 or rs35866072. Importantly, individuals with the MMP-8 rs11225395 CC genotype demonstrated a significant increase in GCa risk when exposed to smoking (OR=4.04, 95%CI=2.28-7.16, p=0.0001), alcohol consumption (OR=2.83, 95%CI=1.64-4.89, p=0.0002), and H. pylori infection (OR=3.53, 95%CI=2.12-5.90, p=0.0001)., Conclusion: The findings indicate that individuals carrying the MMP-8 rs11225395 CC genotype have increased susceptibility to GCa, especially when combined with risk factors, such as smoking, alcohol consumption, and H. pylori infection. These results suggest that MMP-8 genotype-based preventive strategies, including lifestyle alterations and targeted infection treatments, may be valuable in mitigating GCa development., (Copyright © 2024 International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Background/aim: The role of alcohol consumption and aldehyde dehydrogenase 2 (ALDH2) genotype in hepatocellular carcinoma (HCC) development remains uncertain., Materials and Methods: We conducted genotyping of the ALDH2 rs671 single nucleotide polymorphism in 298 patients with HCC and 889 non-cancerous healthy controls. We assessed associations stratified by sex and alcohol consumption status., Results: Distribution of ALDH2 rs671 variant genotypes differed significantly between HCC patients and controls (p trend =0.0311). Logistic regression analyses indicated that compared to the wild-type GG genotype, the heterozygous variant AG genotype and homozygous variant AA genotype conferred 1.22- and 1.77-fold increases in HCC risk (p=0.1794 and 0.0150, respectively). Allelic frequency analysis showed that the A allele was associated with a 1.29-fold increased HCC risk (p=0.0123). Additionally, AA genotype carriers had significantly higher HCC risk than GG genotype carriers among males (p=0.0145) and non-alcohol drinkers (p<0.001)., Conclusion: HCC risk is influenced by ALDH2 genotype, with effects modified by sex and alcohol consumption. Particularly, individuals with the ALDH2 rs671 AA genotype should avoid alcohol consumption, especially males., Competing Interests: All the Authors declare no conflicts of interest regarding this study., (©2024 The Author(s). Published by the International Institute of Anticancer Research.)

Background/aim: Upregulation of matrix metallo-proteinase-8 (MMP-8) serves as a protein-based indicator for predicting nasopharyngeal carcinoma (NPC) metastasis. Nevertheless, the role of MMP-8 genotypes in NPC has never been investigated. This study aimed to explore the involvement of MMP-8 genotypes in NPC development., Materials and Methods: We employed the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) technique to analyze MMP-8 genotypes, specifically C-799T (rs11225395), Val436Ala (rs34009635), and Lys460Thr (rs35866072), in a Taiwanese cohort comprising 208 NPC cases and 416 healthy controls., Results: Individuals with either heterozygous or homozygous variant genotypes of MMP-8 rs11225395 showed no significant change in NPC risk compared to those with the wild-type genotype [odds ratio (OR)=0.97 and 0.79, 95% confidence intervals (95%CI)=0.68-1.38 and 0.46-1.36; p=0.9304 and 0.4736, respectively]. Similarly, there was no significant association between the heterozygous genotypes of MMP-8 rs34009635 and NPC risk (OR=0.66, 95%CI=0.24-1.84; p=0.5738). For MMP-8 rs35866072, all individuals in the study were of the TT genotype. Furthermore, the presence of variant alleles at MMP-8 rs11225395 or rs34009635 did not result in altered NPC risk (OR=0.91 and 0.66, 95%CI=0.71-1.16 and 0.24-1.84, p=0.4876 and 0.5769, respectively). Additionally, no significant association was observed between MMP-8 rs11225395 variant genotypes and NPC risk among individuals regardless of smoking, alcohol consumption, or betel quid chewing habits (all p>0.05)., Conclusion: There was no association between the MMP-8 genotypes rs11225395, rs34009635, or rs35866072 and NPC risk among Taiwanese individuals. Moreover, no combined effects of MMP-8 genotype with smoking, alcohol consumption, or betel quid chewing habits on NPC risk were observed., (Copyright © 2024 International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Background/aim: In current literature, there is a notable lack of studies investigating the role of radiation-sensitive protein 51 (RAD-51) in pterygium diagnosis. Nevertheless, reports indicate elevated expression levels of RAD-51 among recurrent pterygium cases compared to those with primary pterygium. However, the genomic involvement of RAD-51 has yet to be explored in any population. This study aimed to assess the contribution of RAD-51 genotypes to pterygium risk in a representative Taiwanese population., Materials and Methods: RAD-51 rs1801320 genotyping was successfully conducted in a Taiwanese cohort comprising 140 pterygium cases and 280 non-pterygium controls using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) technology., Results: The distribution of RAD-51 rs1801320 genotypes (GG, CG, and CC) in the pterygium group (70.0%, 25.7%, and 4.3%, respectively) did not significantly differ from that in the non-pterygium group (73.6%, 23.6%, and 2.8% for GG, CG, and CC genotypes, respectively; p for trend=0.6337). Carriers of the variant CG and CC RAD-51 rs1801320 genotypes exhibited 1.15- and 1.58-fold increased pterygium risk, respectively (95%CI=0.72-1.84 and 0.53-4.67, p=0.6552 and p=0.5914, respectively). In the dominant model, there appeared to be a slight association between variant genotypes CG and CC and pterygium risk (OR=1.19, 95%CI=0.76-1.87, p=0.0223). Allelic analysis revealed that the RAD-51 rs1801320 variant C allele was not significantly linked to pterygium risk (17.1% versus 14.6%, OR=1.20, 95%CI=0.82-1.78, p=0.3991)., Conclusion: Variant genotypes at RAD-51 rs1801320 were firstly identified to associate with susceptibility to pterygium among Taiwanese individuals. Nonetheless, these findings warrant validation in larger and more diverse populations., (Copyright © 2024, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Background/aim: The overexpression of matrix metalloproteinase-9 (MMP9) has been observed in asthmatic patients, yet the role of MMP9 genotype in determining asthma susceptibility remains unresolved. This study aimed to elucidate the contribution of MMP9 promoter rs3918242 genotype to asthma risk in Taiwan., Materials and Methods: A cohort comprising 453 non-asthmatic healthy controls and 198 asthmatic cases was assembled, and the MMP9 rs3918242 genotypes were determined using polymerase chain reaction-restriction fragment length polymorphism methodology., Results: Our findings indicated that people carrying the variant CT or TT genotype of MMP9 rs3918242 did not demonstrate an elevated risk of asthma compared to wild-type CC carriers (odds ratio=1.28 and 1.72, 95% confidence interval=0.87-1.87 and 0.72-4.13; p=0.2417 and 0.3201, respectively). Furthermore, individuals carrying the T allele at MMP9 rs3918242 did not exhibit a higher risk of asthma than those carrying the C allele (odds ratio=1.31, 95% confidence interval=0.96-1.79, p=0.0869). Interestingly, a positive association was observed between MMP9 rs3918242 CT or TT genotypes and the severity of asthma symptoms among asthmatic patients (p=0.0035)., Conclusion: Although the T allele at MMP9 rs3918242 was not associated with asthma risk, it may serve as a predictor for asthma symptom severity. These findings warrant validation in larger and more diverse populations to further elucidate the significance of MMP9 in asthma etiology., (Copyright © 2024, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Background/aim: Matrix metalloproteinase-2 (MMP-2) has been implicated in the pathogenesis of breast cancer (BC). However, there is limited research on the role of MMP-2 genotypes in BC risk. This study aimed to investigate the associations between two MMP-2 promoter polymorphisms, rs243865 and rs2285053, and BC risk., Materials and Methods: MMP-2 genotypes were analyzed using PCR-based RFLP methodology in a cohort comprising 1,232 BC cases and 1,232 controls., Results: Genotypic frequencies of MMP-2 rs243865 and rs2285053 in controls were consistent with Hardy-Weinberg equilibrium (p=0.3702 and 0.2036, respectively). There were no significant differences in the distribution of rs243865 and rs2285053 genotypes between BC cases and controls (p for trend=0.1602 and 0.2170, respectively). Variant genotypes at rs243865 and rs2285053 appeared to confer a protective effect, although not statistically significant (all p>0.05). Similarly, the variant T allele at rs243865 and rs2285053 showed a non-significant trend towards decreased BC risk (OR=0.84 and 0.89, 95%CI=0.69-1.02 and 0.78-1.02, p=0.0811 and 0.1043, respectively). There was no interaction observed between MMP-2 rs243865 or rs2285053 genotypes and age. Stratified analysis did not reveal significant associations between MMP-2 rs243865 or rs2285053 genotypes and triple-negative breast cancer (TNBC) (p=0.6458 and 0.8745, respectively). Among both TNBC and non-TNBC cases, none of the variant genotypes at rs243865 or rs2285053 showed significant associations with TNBC (all p>0.05)., Conclusion: MMP-2 rs243865 and rs2285053 genotypes appear to have a minimal impact on individual susceptibility to BC or TNBC., (Copyright © 2024, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Prostate cancer (PCa) is a multifactorial disease influenced by genetic, environmental, and immunological factors. Genetic polymorphisms in the interleukin-10 ( IL-10 ) gene have been implicated in PCa susceptibility, development, and progression. This study aims to assess the contributions of three IL-10 promoter single nucleotide polymorphisms (SNPs), A-1082G (rs1800896), T-819C (rs3021097), and A-592C (rs1800872), to the risk of PCa in Taiwan. The three IL-10 genotypes were determined using PCR-RFLP methodology and were evaluated for their contributions to PCa risk among 218 PCa patients and 436 non-PCa controls. None of the three IL-10 SNPs were significantly associated with the risks of PCa ( p all > 0.05) in the overall analyses. However, the GG at rs1800896 combined with smoking behavior was found to significantly increase the risk of PCa by 3.90-fold (95% confidence interval [95% CI] = 1.28-11.89, p = 0.0231). In addition, the rs1800896 AG and GGs were found to be correlated with the late stages of PCa (odds ratio [OR] = 1.90 and 6.42, 95% CI = 1.05-3.45 and 2.30-17.89, p = 0.0452 and 0.0003, respectively). The IL-10 promoter SNP, A-1082G (rs1800896), might be a risk factor for PCa development among smokers and those at late stages of the disease. These findings should be validated in larger and more diverse populations.

Background/aim: The activity and expression of matrix metalloproteinase-7 (MMP7) have been found to be upregulated in the late stages of endometriosis. However, the contribution of MMP7 genotype to endometriosis has seldom been examined. This study aimed to investigate the role of MMP7 promoter A-181G (rs11568818) and C-153T (rs11568819) genotypes in determining personal susceptibility to endometriosis in a Taiwanese cohort., Patients and Methods: In this hospital-based case-control study, MMP7 genotypes were analyzed in 153 endometriosis and 636 individuals without endometriosis using typical polymerase chain reaction-restriction fragment length polymorphism methodology., Results: The statistical analysis revealed that MMP7 rs11568818 genotypes were differentially distributed between the endometriosis and control groups (p for trend=0.0048). Specifically, the MMP7 rs11568818 homozygous variant GG was associated with endometriosis risk compared to the wild-type AA genotype (OR=4.59, 95% CI=1.46-14.48, p=0.0136). However, the MMP7 rs11568818 heterozygous variant AG was not associated with endometriosis risk (OR=1.57, 95% CI=0.97-2.53, p=0.0854). The frequency of than variant allele G of MMP7 rs11568818 was 12.7% in the endometriosis group, significantly higher than the 7.2% observed in the control group (OR=1.90, 95% CI=1.27-2.82, p=0.0021)., Conclusion: MMP7 rs11568818 GG genotype was found to be a novel marker for endometriosis risk in Taiwanese., (Copyright © 2024 International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Background/aim: Hallux valgus (HV) is the most prevalent deformity affecting the forefoot; however, its genetic etiology remains unclear. In the literature, vitamin D receptor (VDR) genotypes have been reported to be associated with the risk of skeletal malformations accompanied by inflammation. This study aimed to examine the hypothesis that VDR genotypes are associated with the risk of HV., Materials and Methods: The VDR rs731236, rs1544410, rs2228570 and rs7975232 genotypes of 150 HV patients and 600 non-HV subjects were determined using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) methodology and examined regarding their associations with HV risk., Results: The results showed that none of the genetic frequency distributions of VDR rs731236, rs1544410, rs2228570, or rs7975232 were significant between the HV cases and non-HV controls (p for trend=0.4055, 0.2170, 0.7220, 0.5509, respectively). Additionally, allelic frequency analysis showed that none of the allelic frequencies of VDR rs731236, rs1544410, rs2228570, or rs7975232 were significantly distributed (p=0.2285, 0.1572, 0.9278, and 0.5547, respectively). Furthermore, stratified analysis showed that no correlation was observed between VDR rs731236 and different age groups (either younger or older than 51) or sex (p=0.3953 and p=0.9576). Moreover, no correlation was found between VDR rs731236 genotype and the risk of HV in individuals within subgroups of height, weight, or body mass index (BMI) (p=0.8317, 0.5346, and p=0.8783, respectively)., Conclusion: VDR rs731236, rs1544410, rs2228570, and rs7975232 may not serve as indicators for a higher risk of HV., (Copyright © 2024, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Background/aim: The up-regulation of matrix metalloproteinase-9 (MMP-9) expression is a characteristic feature observed across various malignancies, including nasopharyngeal carcinoma (NPC). Nevertheless, the influence of MMP-9 genotype in the context of NPC remains underexplored. This study examined the implications of MMP-9 promoter rs3918242 genotypes on the susceptibility to NPC in Taiwan., Materials and Methods: In a cohort comprising 208 NPC cases and 416 healthy controls, genotyping of MMP-9 rs3918242 was conducted utilizing polymerase chain reaction-restriction fragment length polymorphism methodology., Results: Individuals harbouring the variant CT or TT genotype of MMP-9 rs3918242 did not demonstrate a discernible alteration in NPC risk when compared to wild-type CC carriers [odds ratio (OR)=0.83 and 0.79, with 95% confidence intervals (95%CI)=0.56-1.24 and 0.27-2.29; p=0.4205 and 0.8675, respectively]. Moreover, the presence of the variant T allele did not confer a modified risk of NPC (OR=0.84, 95%CI=0.60-1.19, p=0.3761). Intriguingly, a protective effect associated with the MMP-9 rs3918242 CT genotype against NPC risk was discerned among individuals abstaining from betel quid chewing behaviour (OR=0.51, 95%CI=0.30-0.87, p=0.0166). Notably, no significant association was established between the MMP-9 rs3918242 CT or TT genotype and NPC risk among individuals with or without smoking or alcohol consumption habits., Conclusion: Presence of the variant CT or TT genotype at MMP-9 rs3918242 did not appear to substantially contribute to an elevated risk of NPC. Notably, a protective effect against NPC risk was observed in individuals carrying the CT genotype, particularly in those abstaining from betel quid chewing., (Copyright © 2024, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Bladder cancer is an age-related disease, with over three-quarters of cases occurring in individuals aged 65 years and older. Accelerated biological aging has been linked to elevated cancer risks. Epigenetic clocks serve as excellent predictors of biological age, yet it remains unclear whether they are associated with bladder cancer risk. In this large case-control study, we assessed the associations between four well-established epigenetic clocks-HannumAge, HorvathAge, GrimAge, and PhenoAge-and bladder cancer risk. Utilizing single nucleotide polymorphisms (SNPs), which were identified in a genome-wide association study (GWAS), linked to these clocks as instruments, we constructed a weighted genetic risk score (GRS) for each clock. We discovered that higher HannumAge and HorvathAge GRS were significantly associated with increased bladder cancer risk (OR = 1.69 per SD increase, 95% CI, 1.44-1.98, p = 1.56 × 10 -10 and OR = 1.09 per SD increase, 95% CI, 1.00-1.19, p = 0.04, respectively). Employing a summary statistics-based Mendelian randomization (MR) method, inverse-variance weighting (IVW), we found consistent risk estimates for bladder cancer with both HannumAge and HorvathAge. Sensitivity analyses using weighted median analysis and MR-Egger regression further supported the validity of the IVW method. However, GrimAge and PhenoAge were not associated with bladder cancer risk. In conclusion, our data provide the first evidence that accelerated biological aging is associated with elevated bladder cancer risk.

Matrix metalloproteinase (MMP)-2 and -9, which degrade type IV collagen, are linked to cancer invasion and metastasis. Gene polymorphisms in MMP-2 and MMP-9 can influence their function, impacting cancer development and progression. This study analyzed the association between polymorphisms MMP-2 rs243865 (C-1306T), rs2285053 (C-735T), and MMP-9 rs3918242 (C-1562T) with serum concentrations of these enzymes in upper tract urothelial cancer (UTUC) patients. We conducted a case-control study with 218 UTUC patients and 580 healthy individuals in Taiwan. Genotyping was performed using PCR/RFLP on DNA from blood samples, and MMP-2 and MMP-9 serum levels and mRNA expressions in 30 UTUC patients were measured using ELISA and real-time PCR. Statistical analysis showed that MMP-2 rs2285053 and MMP-9 rs3918242 genotypes were differently distributed between UTUC patients and controls ( p = 0.0199 and 0.0020). The MMP-2 rs2285053 TT genotype was associated with higher UTUC risk compared to the CC genotype (OR = 2.20, p = 0.0190). Similarly, MMP-9 rs3918242 CT and TT genotypes were linked to increased UTUC risk (OR = 1.51 and 2.92, p = 0.0272 and 0.0054). In UTUC patients, TT carriers of MMP-2 rs2285053 and MMP-9 rs3918242 showed higher mRNA and protein levels ( p < 0.01). These findings suggest that MMP-2 rs2285053 and MMP-9 rs3918242 genotypes are significant markers for UTUC risk and metastasis in Taiwan.

Background/aim: Renal cell carcinoma (RCC) presents a formidable clinical challenge due to its aggressive behavior and limited therapeutic options. Matrix metalloproteinase-8 (MMP-8) has recently emerged as a potential biomarker and therapeutic target for various cancers. However, the genetic involvement of MMP-8 in RCC has remained largely obscure. This study aimed to elucidate the role of MMP-8 genotypes in RCC susceptibility., Materials and Methods: The polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) technique was employed to scrutinize the genotypes of MMP-8 C-799T (rs11225395), Val436Ala (rs34009635), and Lys460Thr (rs35866072) among 118 RCC patients and 590 controls. Furthermore, potential associations between MMP-8 genotypes and age, sex, smoking, alcohol consumption, hypertension, diabetes, and family history status in relation to RCC risk were assessed., Results: No significant disparities in the distribution of MMP-8 rs11225395, rs34009635, and rs35866072 genotypes were observed between the RCC case and control cohorts (p>0.05). Individuals with CT and TT genotypes at MMP-8 rs11225395 exhibited 0.86- and 0.80-fold RCC risks, respectively (OR=0.57-1.31 and 0.42-1.55, p=0.5585 and 0.6228, respectively). Intriguingly, hypertensive individuals carrying the MMP-8 rs11225395 CT or TT genotype demonstrated an elevated risk for RCC compared to those with wild-type CC genotype (p=0.0440). No interactions of MMP-8 genotypes with age, sex, smoking, alcohol consumption, or diabetes status were evident (all p>0.05). No significant association was discerned for MMP-8 rs34009635 or rs35866072 genotypes., Conclusion: MMP-8 genotypes appear to have a modest influence on individual susceptibility to RCC. Hypertensive patients with the CT or TT MMP-8 rs11225395 genotype may have an elevated risk of RCC., (Copyright © 2024 International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Background/aim: Matrix metalloproteinase-9 (MMP-9) expression is upregulated in various diseases, including lung cancer. However, the role of MMP-9 genotype in lung cancer susceptibility remains uncertain. This study aimed to clarify the contribution of MMP-9 promoter rs3918242 genotypes to the risk of lung cancer in Taiwan., Materials and Methods: The MMP-9 rs3918242 genotypes of 358 lung cancer patients and 716 healthy controls were determined using polymerase chain reaction-restriction fragment length polymorphism methodology., Results: Individuals carrying the variant CT or TT genotype of MMP-9 rs3918242 did not demonstrate an increased risk of lung cancer compared to wild-type CC carriers [odds ratio (OR)=1.11 and 1.85, 95% confidence interval (95%CI)=0.82-1.48 and 0.91-3.76; p=0.5541 and 0.1280, respectively]. Moreover, individuals carrying the T allele did not show a higher lung cancer risk compared to those with the C allele (OR=1.21, 95%CI=0.95-1.54, p=0.1444). However, a significant association was observed between the MMP-9 rs3918242 TT genotype and lung cancer risk among non-smokers (OR=5.48, 95%CI=1.31-22.89, p=0.0181)., Conclusion: The presence of the TT genotype for MMP-9 rs3918242 may indicate an elevated risk of lung cancer among non-smokers., (Copyright © 2024 International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Background/aim: Given the characteristics of Serratia marcescens (S. marcescens), this study aimed at investigating its presence in the hands and contact lens cases of orthokeratology wearers, along with the status of bacterial contamination., Patients and Methods: The 39 patients received the questionnaires about the background of orthokeratology and hygiene habits. A total of 39 contact lens cases and 39 hand samples from the patients were collected at Show Chwan Memorial Hospital from June to August in 2020 and sent to National Chung Cheng University for DNA extraction and PCR identification., Results: The results indicated a detection rate of 5.13% for S. marcescens in the contact lens cases and 12.82% in the hand samples. Additionally, 66.67% of contact lens case samples and 30.77% of hand samples found positive for 16s bacterial amplicons. The relationship between hand contamination and the duration of contact lens usage were revealed for both S. marcescens (p=0.021) and 16s bacterial amplicons (p=0.048)., Conclusion: The results indicated that hand hygiene is more critical than focusing on contact lens hygiene when it comes to preventing S. marcescens infections. Nevertheless, both proper hand and contact lens hygiene practices can reduce the detection of bacterial eye pathogens, especially a common intestinal bacterium., (Copyright © 2024, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

We conducted the first genome-wide association study (GWAS) of prostate cancer (PCa) in Taiwan with 1844 cases and 80,709 controls. Thirteen independent single-nucleotide polymorphisms (SNPs) reached genome-wide significance (p < 5 × 10 -8 ). Among these, three were distinct from previously identified loci: rs76072851 in CORO2B gene (15q23), odds ratio (OR) = 1.54, 95% confidence interval (CI), 1.36-1.76, p = 5.30 × 10 -11 ; rs7837051, near two long noncoding RNA (lncRNA) genes, PRNCR1 and PCAT2 (8q24.21), OR = 1.41 (95% CI, 1.31-1.51), p = 8.77 × 10 -21 ; and rs56339048, near an lncRNA gene, CASC8 (8q24.21), OR = 1.25 (95% CI, 1.16-1.35), p = 2.14 × 10 -8 . We refined the lead SNPs for two previously identified SNPs in Taiwanese: rs13255059 (near CASC8), p = 9.02 × 10 -43 , and rs1456315 (inside PRNCR1), p = 4.33 × 10 -42 . We confirmed 35 out of 49 GWAS-identified East Asian PCa susceptibility SNPs. In addition, we identified two SNPs more specific to Taiwanese than East Asians: rs34295433 in LAMC1 (1q25.3) and rs6853490 in PDLIM5 (4q22.3). A weighted genetic risk score (GRS) was developed using the 40 validated SNPs and the area under the receiver-operating characteristic curve for the GRS to predict PCa was 0.67 (95% CI, 0.63-0.71). These identified SNPs provide valuable insights into the molecular mechanisms of prostate carcinogenesis in Taiwan and underscore the significant role of genetic susceptibility in regional differences in PCa incidence., (© 2024 Wiley Periodicals LLC.)

Background/aim: Numerous studies have reported the over-expression of the radiation-sensitive protein 51 (RAD51) in various types of cancer. However, the role of RAD51 genotypes in lung cancer remains largely unknown. This study aimed to assess the impact of the common variant RAD51 rs1801320 (G-135C) genotypes on the risk of lung cancer in Taiwan., Materials and Methods: The contribution of RAD51 rs1801320 genotypes to lung cancer risk was investigated in a cohort comprising 358 lung cancer patients and 716 age- and sex-matched healthy controls, utilizing polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) methodology., Results: The analysis revealed that among the control subjects, the percentages of GG, CG, and CC genotypes of RAD51 rs1801320 were 73.2%, 24.3%, and 2.5%, respectively. Among the lung cancer patients, these percentages were 71.0%, 25.1%, and 3.9%, respectively (p for trend=0.4075). Allelic frequency distributions showed no significant association between the C allele of RAD51 rs1801320 and lung cancer risk determination (p=0.2987). Specifically, the RAD51 rs1801320 CC genotypes were associated with an elevated risk of lung cancer among males [adjusted odds ratio (aOR)=2.28, 95% confidence interval (95%CI)=1.03-4.87] and smokers (aOR=2.93, 95%CI=1.23-5.87), but not among females and non-smokers., Conclusion: The RAD51 rs1801320 CC genotype was identified as a risk factor for elevated lung cancer risk in males and smokers. This genotype may serve as a molecular biomarker at the DNA level for early detection and prediction of lung cancer in Taiwan., (Copyright © 2024 International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Background/aim: The capacity for non-homologous end-joining (NHEJ) repair plays a pivotal role in maintaining genome stability and in carcinogenesis. However, there is little literature on the involvement of NHEJ-related genes in childhood acute lymphocytic leukemia (ALL). Our study aimed to elucidate the impact of polymorphisms of X-ray repair cross-complementing group 4 (XRCC4) (rs6869366, rs2075685, rs2075686, rs28360071, rs3734091, rs28360317, rs1805377), XRCC5 (rs828907, rs11685387, rs9288518), XRCC6 (rs5751129, rs2267437, rs132770, rs132774), XRCC7 rs7003908, and DNA ligase IV (LIG4) rs1805388, on the odds of childhood ALL., Materials and Methods: Genotypes NHEJ-related genes of 266 cases and 266 controls were determined, and the genotype-phenotype correlation was investigated by examining mRNA transcript expression and the capacity for overall and precise NHEJ repair., Results: The variant genotypes of XRCC4 rs3734091, rs28360071, XRCC5 rs828907, and XRCC6 rs5751129 were significantly associated with increased odds of childhood ALL. Further analysis based on susceptibility genotypes showed no significant differences in mRNA transcript expression levels among childhood ALL cases with various putative high-risk genotypes, except XRCC6 rs5751129. Moreover, the overall NHEJ repair capacity was similar among carriers of different XRCC4, XRCC5, and XRCC6 genotypes. However, it is worth noting that individuals carrying the variant C allele at XRCC6 rs5751129 exhibited lower precise NHEJ repair capacity compared to those with the wild-type T allele., Conclusion: Our study identified significant associations between XRCC4 rs3734091, rs28360071, XRCC5 rs828907, and XRCC6 rs5751129 genotypes and childhood ALL. Notably, lower transcriptional expression and reduced precise NHEJ repair capacity were observed in patients carrying the C allele of XRCC6 rs5751129. Further investigations are required to gain deeper insights into childhood ALL development., (Copyright © 2024, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Background/aim: In the literature, the studies about the role of matrix metalloproteinase-2 (MMP-2) in pterygium diagnosis are mainly based on its protein expression. The role of MMP-2 variants has never been examined. The aim of this study was to examine the association of MMP-2 genotypes with pterygium risk., Materials and Methods: MMP-2 rs243865 and rs2285053 were genotyped in 140 pterygium cases and 280 non-pterygium controls by typical polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) genotyping technology., Results: The genotypic frequency of MMP-2 rs243865 CC, CT and TT were 86.4%, 12.9% and 0.7% in the pterygium group and 81.1%, 17.1% and 1.8% in the non-pterygium group (p for trend=0.3389). The variant CT and TT carriers had a 0.70- and 0.38-fold pterygium risk (95%CI=0.39-1.26 and 0.04-3.25, p=0.2982 and 0.6686, respectively). As for MMP-2 rs2285053, the genotypic frequency of CC, CT and TT were 67.1%, 28.6% and 4.3% in the pterygium group, non-significantly different from those in non-pterygium group (p for trend=0.7081). The CT and TT carriers had a 0.88- and 0.71-fold pterygium risk (95%CI=0.56-1.38 and 0.27-1.88, p=0.6612 and 0.6456, respectively). The allelic analysis results showed that MMP-2 rs243865 variant T allele was not associated with pterygium risk (7.1% versus 10.4%, OR=0.67, 95%CI=0.39-1.13, p=0.1649). As for MMP-2 rs2285053, the T allele was not associated with pterygium risk either (18.6% versus 21.1%, OR=0.85, 95%CI=0.59-1.23, p=0.4136)., Conclusion: The genotypes at MMP-2 rs243865 or rs2285053 played minor role in determining individual susceptibility for pterygium among Taiwanese., (Copyright © 2024, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Background/aim: Matrix metalloproteinase-1 (MMP-1) expression has been documented as an influential contributor to the intricate milieu of allergic airway inflammation, tissue remodeling, and the exacerbation of asthma's severity. However, the genetic role underlying MMP-1 in the context of asthma has remained enigmatic, with its full implications yet to be unveiled. Considering this, our research was designed to investigate the association of MMP-1 -1607 rs1799750 and the propensity for asthma severity., Patients and Methods: As a case-control investigation, our study enrolled 198 individuals diagnosed with asthma and age- and sex-matched 453 non-asthmatic controls. The genotypes of MMP-1 rs1799750 were determined utilizing the polymerase chain reaction-restriction fragment length polymorphism methodology., Results: The frequency distributions of 2G/2G, 1G/2G and 1G/1G genotypes at MMP-1 rs1799750 were 49, 42.9, and 8.1%, respectively, among the patients with asthma. This pattern was not different from that of controls (43.7, 46.8, and 9.5%, respectively) (p for trend=0.4486). The allelic frequency pertaining to the variant 1G allele within the asthma group was 29.5%, with a non-significant disparity compared to the 32.9% in the control group (p=0.2596). Noticeably, there was a positive association between MMP-1 rs1799750 2G/1G and 1G/1G genotypes with asthma severity (p=0.0060)., Conclusion: Our research indicated that the presence of MMP-1 rs1799750 1G allele might not be the sole arbiter of an individual's susceptibility to asthma, yet its potential to function as a discerning prognostic marker for the severity of asthma emerged as a noteworthy finding deserving attention and further exploration., (Copyright © 2024, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Background/aim: 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., Materials and Methods: 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., Results: 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., Conclusion: 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., (Copyright © 2024, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Background/aim: X-linked hypophosphatemia (XLH), the most common form of hereditary rickets, results from loss-of-function mutations in the phosphate-regulating PHEX gene. Elevated fibroblast growth factor 23 (FGF23) contributes to hypophosphatemia in XLH. This study aimed to characterize PHEX variants and serum FGF23 profiles in Taiwanese patients with XLH., Patients and Methods: We retrospectively reviewed the records of 102 patients clinically suspected of having hypophosphatemic rickets from 2006 to 2022. Serum intact Fibroblast growth factor-23 (iFGF23) levels were measured on clinic visit days. PHEX mutations were identified using Sanger sequencing, and negative cases were analyzed using whole-exome sequencing., Results: The majority (92.1%) of patients exhibited elevated FGF23 compared with normal individuals. Among 102 patients, 44 distinct PHEX mutations were identified. Several mutations recurred in multiple unrelated Taiwanese families. We discovered a high frequency of novel PHEX mutations and identified variants associated with extreme FGF23 elevation and tumorigenesis., Conclusion: Our findings revealed the PHEX genotypic variants and FGF23 levels in Taiwanese patients with XLH. These results are crucial given the recent approval of burosumab, a monoclonal FGF23 antibody, for XLH therapy. This study provides key insights into the clinical management of XLH in Taiwan., (Copyright © 2024, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Background/aim: While numerous biomarkers associated with genetic susceptibility to colorectal cancer (CRC) have been identified and validated through epidemiological studies, the specific influence of DNA ligase 4 (Lig4) genotypes remains unexplored. This study aimed to elucidate the hitherto unexamined relationship between Lig4 genotypes and CRC risk., Materials and Methods: The genotypes of Lig4 rs1805388 were determined applying the polymerase chain reaction-restriction fragment length polymorphism methodology. The potential association between these genotypes and CRC risk was assessed in a Taiwanese population comprising 362 CRC cases and an equal number of age- and sex-matched controls., Results: In the genotypic analysis, the distribution of CC, CT, and TT genotypes for Lig4 rs1805388 among CRC cases was 54.7%, 38.1%, and 7.2%, respectively. This distribution was not significantly different from the controls, which exhibited genotypic frequencies of 57.2%, 36.7%, and 6.1%, respectively (p for trend=0.7314). Analysis of allelic distribution indicated that individuals carrying the T allele of Lig4 rs1805388 displayed a slightly elevated CRC risk compared to those carrying the C allele (odds ratio=1.10, 95% confidence interval=0.87-1.39, p=0.4685)., Conclusion: The variant genotypes of Lig4 rs1805388 may not serve as predictive markers for CRC risk in the Taiwanese population., (Copyright © 2024, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Background/aim: Acid sphingomyelinase deficiency (ASMD) is a rare lysosomal storage disorder characterized by sphingomyelin accumulation causing progressive lung disease, respiratory failure, and death., Patients and Methods: This retrospective observational study used the TriNetX database of electronic health records for 15,108 patients with ASMD from 2000-2020. After exclusions, 8,980 individuals were followed for 10 or 20 years. Outcomes included incidence and prevalence of respiratory disorders. Associations of age, sex and race were assessed., Results: Nearly all respiratory outcomes increased significantly over 20 versus 10 years. Other respiratory disorders, specified respiratory disorders and secondary pulmonary hypertension exhibited the greatest increases, reflecting progressive lung damage in ASMD. While outcomes were poor overall, older age, male sex, and racial minority status associated with greater risks, indicating differences in disease progression or care., Conclusion: This study confirms the progressive nature of ASMD and need for close monitoring and treatment of pulmonary complications to reduce long-term morbidity and mortality. Genetic testing enabling diagnosis even for milder, adult-onset forms is critical to optimize outcomes., (Copyright © 2024, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

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 TIMP-2 genotypes with BC risk are rather limited. In this study, contribution of TIMP-2 rs8179090, rs4789936, rs2009196 and rs7342880 genotypes to BC risk was examined among Taiwan's BC population. TIMP-2 genotypic profiles were revealed among 1232 BC cases and 1232 controls about their contribution to BC using a PCR-based RFLP methodology. The TIMP-2 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, p = 0.0001). Allelic analysis showed that C allele carriers have increased risk for BC (OR = 1.39, 95%CI = 1.20-1.62, p = 0.0001). Genotypic together with allelic analysis showed that TIMP-2 rs4789936, rs2009196 or rs7342880 were not associated with BC risk. Stratification analysis showed that TIMP-2 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.

Background/aim: Interleukin 8 (IL-8) is highly expressed in refractory acute lymphocytic leukemia (ALL) cells. This study aimed to investigate the contribution of IL-8 polymorphisms to the risk of childhood ALL., Materials and Methods: The genotypes of IL-8 rs4073, rs2227306, rs2227543, and rs1126647 were determined in 266 childhood ALL cases and 266 controls using the PCR-RFLP method. Additionally, we assessed whether the interactions of these genotypes with age and sex contributed to childhood ALL risk., Results: The distributions of genotypic and allelic frequencies of IL-8 rs4073, rs2227306, rs2227543, and rs1126647 were not significantly different between childhood ALL cases and controls (all p>0.05). However, carriers of the variant AA genotype at IL-8 rs4073 had a significantly higher risk of childhood ALL among those aged ≤3.5 years and among girls (OR=2.39 and 3.32, 95%CI=1.21-4.73 and 1.51-7.30, p=0.0182 and 0.0042, respectively). In the stratification analysis, IL-8 rs4073 AT and AA genotypes were associated with higher childhood ALL risk classification and shorter survival time (OR=2.21 and 4.13, 95%CI=1.29-3.78 and 1.87-9.10, p=0.0054 and 0.0002, respectively). There was no positive association for rs2227306, rs2227543, or rs1126647 (all p>0.05)., Conclusion: The A allele of IL-8 rs4073 can serve as a diagnostic predictor for childhood ALL, but only in girls and patients younger than or equal to 3.5 years old. More importantly, it can serve as a prognostic marker for high-risk classification and shorter survival time. Further validation studies can help extend the use of this prognostic predictor in clinical practice., (Copyright © 2023 International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Background/aim: Fabry disease, an X-linked lysosomal storage disorder, causes progressive globotriaosylceramide accumulation in cells throughout the body. Characteristic multiorgan manifestations include renal dysfunction (Fabry nephropathy) and associated urinary tract complications. Enzyme replacement therapy (ERT) has been available since 2001, but contemporary real-world data are lacking regarding Fabry nephropathy risks and treatment outcomes., Patients and Methods: This retrospective cohort study analyzed electronic medical records data for 10,637 Fabry disease patients from the TriNetX research database. Kidney and urinary tract outcomes were evaluated over two decades, 2000-2010 and 2011-2020. Outcomes assessed included chronic kidney disease (CKD), urinary tract infections, urinary incontinence, obstruction, renal insufficiency, and end-stage renal disease (ESRD)., Results: The prevalence of stage 4-5 CKD nearly doubled between 2000-2010 and 2011-2020, while ESRD prevalence rose over 4-fold. Incidence rates showed similar marked elevations across renal and urologic complications. Females and Black patients experienced disproportionate escalations in kidney and urinary tract morbidity., Conclusion: This large cohort study revealed significantly increased Fabry nephropathy and associated urologic complications over the past two decades, contradicting expectations of reduced morbidity with ERT availability. The findings highlight needs to optimize screening, treatment strategies, monitoring practices, and address disparities to curb rising disease burden and improve patient outcomes., (Copyright © 2023, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Background/aim: The expression of matrix metalloproteinase 9 (MMP9) is elevated in various renal diseases, including renal cell carcinoma. However, the role of MMP9 genotype in this context remains unclear. This study aimed to investigate the association between MMP9 promoter rs3918242 genotypes and the risk of renal cell carcinoma., Materials and Methods: The MMP9 rs3918242 genotypes of 118 patients with renal cell carcinoma and 590 healthy subjects were determined using the polymerase chain reaction-restriction fragment length polymorphism method., Results: The results indicated that individuals carrying the CT or TT genotype of MMP9 rs3918242 did not exhibit an increased risk of renal cell carcinoma compared to wild-type CC carriers (odds ratio=1.20 and 2.68, 95% confidence interval=0.75-1.92 and 0.89-8.03; p=0.5270 and 0.1420, respectively). However, individuals with the CT and TT genotypes had a higher prevalence of renal cell carcinoma than those with the CC genotype when they also had hypertension (p=0.0010), diabetes (p=0.0010), or a family history of cancer (p<0.00001). No correlation was observed between MMP9 rs3918242 genotypic distribution and age (60 years or younger vs. older than 60 years) or sex (both p>0.05). Additionally, no correlation was found between MMP9 rs3918242 genotype and the risk of renal cell carcinoma in individuals with smoking or alcohol consumption habits., Conclusion: Carrying the T allele for MMP9 rs3918242 may predict a higher risk of renal cell carcinoma among individuals diagnosed with hypertension, diabetes, or with a family history of cancer., (Copyright © 2023, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Background/aim: Turner syndrome confers increased cancer susceptibility; however, large-scale epidemiological evidence is lacking. This study aimed to analyze the incidence and prevalence of various malignancies in patients with Turner syndrome over 20 years of age to inform screening strategies., Patients and Methods: We performed a retrospective cohort analysis of 11,502 patients with Turner syndrome from 2000 to 2020 utilizing the TriNetX research network database. The outcomes encompassed the incidence and prevalence of 20 cancers. Stratified analyses were used to evaluate variations in age, sex, and race., Results: Key findings demonstrated markedly elevated risks of breast (1.7%), colon (1.0%), renal (0.4%), gonadoblastoma (0.4%), and other cancers. Significant demographic variations were observed in the incidence of cancers, such as gonadoblastoma, renal, and colon cancer., Conclusion: This large real-world study offers novel insights into the spectrum of cancer risk across adulthood in Turner syndrome. Our findings elucidate Turner syndrome's complex cancer phenotype to inform clinical decision-making, prognostication, and tailored screening strategies to ultimately advance patient care., (Copyright © 2023 International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Interleukin-8 (IL-8), a pro-inflammatory cytokine, is upregulated in CRC and plays an important role in its development and progression. Genetic variants in the IL-8 gene may impact the risk of CRC by modulating IL-8 levels. Our primary objective was to investigate the role of IL-8 genotypes in the development of CRC. To accomplish this, we employed the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method to analyze the genotypes of IL-8 rs4017, rs2227306, rs2227543, and rs1126647 in 362 CRC patients and 362 controls. Additionally, we evaluated the interactions between these genotypes and factors such as age, gender, smoking, alcohol consumption, and body mass index (BMI) status in relation to the risk of CRC. Furthermore, we utilized quantitative reverse transcription-PCR to measure the serum IL-8. The results demonstrated a significant difference in the distribution of rs4017 genotypes between the control and case groups ( p for trend = 0.0059). Logistic regression analysis revealed that individuals with variant AA genotype had a 1.92-fold higher CRC risk (95% confidence interval [CI] = 1.28-2.89, p = 0.0023). Moreover, carriers of the IL-8 rs4017 AT + AA genotypes exhibited a significant association with CRC risk (odds ratio [OR] = 1.39, 95% CI = 1.02-1.91, p = 0.0460). Additionally, individuals with IL-8 rs4017 AA genotype displayed significantly elevated serum IL-8 compared to those with TT genotype at a 1.73-fold level ( p < 0.0001), indicating a correlation between genotype and phenotype. In conclusion, the genotypes of IL-8 rs4017, along with their associated expression levels, can potentially serve as predictive markers for the risk of CRC.

The aberrant activation of signaling pathways contributes to cancer cells with metabolic reprogramming. Thus, targeting signaling modulators is considered a potential therapeutic strategy for cancer. Subcellular fractionation, coimmunoprecipitation, biochemical analysis, and gene manipulation experiments revealed that decreasing the interaction of kirsten rat sarcoma viral oncogene homolog (KRAS) with p110α in lipid rafts with the use of naringenin (NGN), a citrus flavonoid, causes lipid raft-associated phosphatidylinositol 3-kinase (PI3K)-GTP-ras-related C3 botulinum toxin substrate 1 (Rac1)-protein kinase B (Akt)-regulated metabolic dysfunction of glycolysis and mitochondrial oxidative phosphorylation (OXPHOS), leading to apoptosis in human nasopharyngeal carcinoma (NPC) cells. The use of lethal-7g ( let-7g ) mimic and let-7g inhibitor confirmed that elevated let-7g resulted in a decrease in KRAS expression, which attenuated the PI3K-Rac1-Akt-BCL-2/BCL-x L -modulated mitochondrial energy metabolic functions. Increased let-7g depends on the suppression of the RNA-specificity of monocyte chemoattractant protein-induced protein-1 (MCPIP1) ribonuclease since NGN specifically blocks the degradation of pre-let-7g by NPC cell-derived immunoprecipitated MCPIP1. Converging lines of evidence indicate that the inhibition of MCPIP1 by NGN leads to let-7g upregulation, suppressing oncogenic KRAS-modulated PI3K-Rac1-Akt signaling and thereby impeding the metabolic activities of aerobic glycolysis and mitochondrial OXPHOS., Competing Interests: The authors declare no conflict of interest.

Background/aim: Gaucher disease (GD) is a rare lysosomal storage disorder that can involve the lungs and pulmonary vasculature. The long-term effects of GD on respiratory health remain unclear due to limited data on the natural history of this disease. We analyzed electronic health records for 11,004 patients with GD over 10-20 years to determine the incidence of pulmonary hypertension (PH), lung disease, and other respiratory comorbidities and better understand disease course to guide management., Patients and Methods: We conducted a retrospective cohort study using the TriNetX research database of 130 million international patients. The incidence of primary/secondary PH, pulmonary heart disease, interstitial/obstructive/restrictive lung disease, pulmonary hemorrhage, and pulmonary embolism was assessed in patients with GD from 2000-2020., Results: Incidence rates of all conditions assessed increased from 10 to 20 years of follow-up. Excess risk of PH, lung disease, and pulmonary hemorrhage was significantly higher in GD patients after 20 versus 10 years., Conclusion: Extended follow-up in GD is associated with substantially higher risks of PH, lung disease and other respiratory comorbidities, highlighting the need for close monitoring and early intervention to mitigate long-term pulmonary decline. Improved understanding of mechanisms driving respiratory deterioration can support the development of novel treatments to optimize outcomes in this population at high risk of pulmonary morbidity and mortality., (Copyright © 2023, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Background/aim: This study aimed to investigate the involvement of matrix metalloproteinase-8 (MMP-8) genotypes in the development of colorectal cancer (CRC)., Materials and Methods: The polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) technique was used to analyze the genotypes of MMP-8 C-799T (rs11225395), Val436Ala (rs34009635), and Lys460Thr (rs35866072) in 362 patients with CRC and 362 controls. Additionally, the potential associations between these genotypes and factors such as age, sex, smoking, alcohol consumption, and body mass index (BMI) status in relation to CRC risk were also assessed., Results: No significant differences in the distribution of MMP-8 rs11225395 genotypes were found between the control and case groups (p for trend=0.3836). Logistic regression analysis demonstrated that individuals with the MMP-8 rs11225395 variant CT and TT genotypes had a 0.83 and 0.77-fold risk of CRC, respectively. Moreover, carriers of the rs11225395 CT+TT genotypes were not associated with CRC risk either (p=0.2063). Furthermore, individuals with the MMP-8 rs11225395 TT genotype exhibited significantly lower odds of CRC risk compared to those with the CC genotype among non-smokers (p=0.0379). No significant associations were observed with respect to MMP-8 rs34009635 or rs35866072., Conclusion: The analyzed genotypes of MMP-8 play a minor role in determining individual susceptibility to CRC risk., (Copyright © 2023 International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Background/aim: Impaired non-homologous end-joining DNA repair capacity may have a significant role in maintaining genome integrity and triggering carcinogenesis. However, the specific impact of DNA ligase 4 (Lig4) genotypes remains unclear. This study aimed to assess the contribution of Lig4 genotypes to the risk of developing lung cancer., Materials and Methods: Polymerase chain reaction-restriction fragment length polymorphism analysis was used to examine the genotypes of Lig4 rs1805388, and their association with lung cancer risk was evaluated in a case-control study consisting of 358 lung cancer cases and 716 age- and sex-matched cancer-free control subjects., Results: The distribution of CC, CT, and TT genotypes for Lig4 rs1805388 among the cases was 45.0%, 41.6%, and 13.4%, respectively, compared to 58.0%, 36.3%, and 5.7% among the controls (p for trend=1.98×10 -6 ). Allelic analysis indicated that individuals carrying the T-allele for Lig4 rs1805388 had a 1.66-fold higher risk of developing lung cancer compared to those carrying the wild-type C-allele [95% confidence interval (CI)=1.36-2.02, p=4.04×10 -7 ]. Moreover, a significant interaction was observed between the Lig4 rs1805388 genotype and smoking status (p=1.32×10 -7 )., Conclusion: These findings suggest that the CT and TT variant genotypes of Lig4 rs1805388, combined with cigarette smoking, may contribute to a higher risk of developing lung cancer., (Copyright © 2023 International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Prostate cancer (PCa) is the most prevalent men's cancer in America and Western countries. No effective therapies are currently available for PCa aggressiveness, including castration-resistant progression (CRPC). This study aims at evaluation of the prospective efficacy and the molecular mechanism of scandenolone (SCA), a natural isoflavone, in PCa progression. SCA suppressed cell viability and progression and induced apoptosis in PCa cells. SCA inhibited the expression of lipogenesis and cholesterogenesis related key genes. Through inhibition of these metabolic genes, SCA decreased the levels of fatty acids, lipid droplets and cholesterols in PCa cells. Moreover, SCA enhanced the expression of antioxidant factors, including Nrf2, HO-1, catalase and SOD-1, and reduced the ROS levels in PCa cells. Substantially, SCA displayed the potential efficacy on CRPC tumors. This paper offers a new insight into the underlying molecular basis of SCA in PCa cells. By coordinated impairment of the metabolic and signaling vulnerabilities, including lipogenesis, cholesterogenesis, ROS and the AR/PSA axis, SCA could be applied as a novel and promising remedy to cure malignant PCa., Competing Interests: Declaration of Competing Interest None., (Copyright © 2023 The Authors. Published by Elsevier Masson SAS.. All rights reserved.)

We aimed to investigate the association between genotypes for mir146a and mir196a-2 and the risk of developing colorectal cancer (CRC). We used polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) to determine the mir146a rs2910164 and mir196a-2 rs11614913 genotypes in 362 CRC patients and 362 controls. We also assessed the interactions between these genotypes and age, gender, smoking, alcohol consumption, and BMI status on CRC risk. Additionally, the serum expression level of mir196a-2 was quantified using quantitative reverse transcription-PCR. Our findings demonstrated that among the controls, the proportions of TT, CT, and CC genotypes of mir196a-2 rs11614913 were 32.3%, 48.1%, and 19.6%, respectively. As for the cases, the proportions were 24.6%, 45.0%, and 30.4%, respectively. Logistic regression analysis revealed that the CC genotype carriers had a 2.04-fold increased risk (95% confidence interval [CI] = 1.36-3.06, p = 0.0008). Furthermore, carriers of the CT + CC genotypes also exhibited a significant association with CRC risk (odds ratio [OR] = 1.46, 95% CI = 1.06-2.03, p = 0.0261). Moreover, carriers of the CC genotype had significantly higher serum levels of mir196a-2 compared to those with the TT genotype ( p < 0.0001), indicating a genotype-phenotype correlation. No association was found regarding mir146a rs2910164. In conclusion, mir196a-2 rs2910164 genotypes, along with their associated expression, can serve as predictive markers for CRC risk.

Background/aim: Impaired DNA repair capacity may play a critical role in genome instability and carcinogenesis. However, the impact of DNA ligase 1 (Lig1) genotypes on tumorigenesis remains unclear. This study aimed to investigate the contribution of Lig1 rs20579 genotypes to the risk of developing lung cancer, and review the related literature., Materials and Methods: Polymerase chain reaction-restriction fragment length polymorphism analysis was used to determine the genotypes of Lig1 rs20579 and evaluate their association with lung cancer risk among 358 lung cancer cases and 716 age- and sex-matched cancer-free control subjects., Results: The distribution of GG, AG, and AA genotypes for Lig1 rs20579 was 77.1%, 20.8%, and 2.1% among the controls, and 76.0%, 21.5%, and 2.5% among the lung cancer cases (p for trend=0.8686). There was no significant difference in the distribution of AG and AA genotypes between the two groups (p=0.8257 and 0.8098, respectively). Allelic frequency analysis indicated that individuals carrying the variant A allele for Lig1 rs20579 had a non-significant 1.07-fold higher risk of developing lung cancer than those carrying the wild-type G allele [95% confidence interval (CI)=0.82-1.40, p=0.6639]. Furthermore, no differential distribution of the Lig1 rs20579 genotype was found among non-smokers (p=0.9910) or smokers (p=0.9001)., Conclusion: In contrast to Americans, Lig1 rs20579 genotypes do not appear to play a critical role in determining susceptibility to lung cancer among Taiwanese individuals., (Copyright © 2023, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Defects in the non-homologous end-joining (NHEJ) DNA repair pathway lead to genomic instability and carcinogenesis. However, the roles of individual NHEJ genes in nasopharyngeal carcinoma (NPC) etiology are not well-understood. The aim of this study was to assess the contribution of NHEJ genotypes, including XRCC4 (rs6869366, rs3734091, rs28360071, rs28360317, rs1805377), XRCC5 (rs828907, rs11685387, rs9288518), XRCC6 (rs5751129, rs2267437, rs132770, rs132774), XRCC7 rs7003908, and Ligase4 rs1805388, to NPC risk, with 208 NPC patients and 416 controls. Genotype-phenotype correlations were also investigated by measuring mRNA and protein expression in adjacent normal tissues and assessing the NHEJ repair capacity in blood lymphocytes from 43 NPC patients. The results showed significant differences in the distributions of variant genotypes at XRCC4 rs3734091, rs28360071, and XRCC6 rs2267437 between the cases and controls. The variant genotypes of these three polymorphisms were associated with significantly increased NPC risks. NPC patients with the risk genotypes at XRCC6 rs2267437 had significantly reduced expression levels of both mRNA and protein, as well as a lower NHEJ repair capacity, than those with the wild-type genotype. In conclusion, XRCC4 rs3734091, rs28360071, and XRCC6 rs2267437 in the NHEJ pathway were associated with NPC susceptibility. XRCC6 rs2267437 can modulate mRNA and protein expression and the NHEJ repair capacity.

Background/aim: Arsenic trioxide (As 2 O 3 ), a potent toxin in traditional Chinese medicine, has been utilized as an anticancer agent in Chinese culture for over a millennium. Betulin, commonly extracted from the bark of birch trees, has been identified for its pharmacological properties, including antibacterial, anti-inflammatory, antitumor, and antiviral activities. The aim of this study was to determine the efficacy and underlying anticancer signaling cascade induced by As 2 O 3 and betulin in neuroblastoma cells., Materials and Methods: SK-N-SH cells were treated with As 2 O 3 with or without betulin. Cell viability and apoptotic signaling were assessed using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay, measurement of mitochondrial membrane potential (MMP) loss and reactive oxygen species (ROS), and quantitative western blotting analysis. Student's t-test in addition to one- or two-way analysis of variance was used to examine significant differences between comparison groups., Results: The combined treatment of As 2 O 3 plus betulin was more effective than single treatments in suppressing cell viability and induction of apoptosis, which correlated well with elevated ROS levels. The apoptotic signaling cascade of As 2 O 3 plus betulin was revealed as ROS elevation and relative loss of MMP, leading to the cleavage of caspase-3 and -9. As 2 O 3 plus betulin treatment also reduced the expression of BCL2 apoptosis regulator, BH3-interacting domain death agonist, and BCL2-like-1., Conclusion: The novel combination of As 2 O 3 plus betulin has the potential to serve as a practical anti-neuroblastoma drug., (Copyright © 2023 International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

The aim of this study was to investigate the association between single-nucleotide polymorphisms (SNPs) in mir146a and mir196a and bladder cancer (BLCA) risk in Taiwan. The genotypes of mir146a rs2910164 and mir196a rs11614913 were determined in 375 BLCA patients and 375 healthy controls using PCR-RFLP methodology, and their associations with BLCA risk were evaluated. The study also measured the serum expression level of mir146a using quantitative RT-PCR. The results showed that the distributions of CC, CG and GG genotypes of mir146a rs2910164 were 31.7%, 45.6% and 22.7% in the control group, and 21.9%, 44.3% and 33.8% in the case group, respectively. In logistic regression analyses, the heterozygous variant genotype CG carriers showed a marginally significant association with increased BLCA risk (OR = 1.41, 95% CI = 0.99-2.01), while the homozygous variant genotype GG carriers had a 2.17-fold increased risk of BLCA (OR = 2.17, 95%CI = 1.46-3.21). Moreover, carriers of the GG/CG genotypes had significantly higher serum levels of mir146a than those with the CC genotype ( p < 0.0001), indicating a genotype-phenotype correlation. In contrast, mir196a rs11614913 was not associated with BLCA risk. Therefore, the genotypes of mir146a rs2910164 may serve as a useful biomarker for predicting the risk of BLCA.