Non-homologous End-joining Genotype, mRNA Expression, and DNA Repair Capacity in Childhood Acute Lymphocytic Leukemia.

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.

Interleukin-8 Rs4073 Genotypes as Prognostic Predictors for Childhood Acute Lymphocytic Leukemia.

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.

Impact of Mir196a-2 Genotypes on Colorectal Cancer Risk in Taiwan.

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.

Involvement of Mitochondrial Damage and Oxidative Stress in Apoptosis Induced by Betulin Plus Arsenic Trioxide in Neuroblastoma Cells.

BACKGROUND/AIM: Arsenic trioxide (As2O3), 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 As2O3 and betulin in neuroblastoma cells. MATERIALS AND METHODS: SK-N-SH cells were treated with As2O3 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 As2O3 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 As2O3 plus betulin was revealed as ROS elevation and relative loss of MMP, leading to the cleavage of caspase-3 and -9. As2O3 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 As2O3 plus betulin has the potential to serve as a practical anti-neuroblastoma drug.

Significant Contribution of Interleukin-18 Genotypes to Childhood Acute Lymphocytic Leukemia Risk in Taiwanese.

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.

The Contribution of Matrix Metalloproteinase-7 Promoter Genotypes to Hepatocellular Carcinoma Susceptibility.

BACKGROUND/AIM: Metalloproteinase-7 (MMP-7) has been previously found to be up-regulated in hepatocellular carcinoma (HCC) specimens and cells, favoring epithelial-mesenchymal transition. However, the contribution of MMP-7 genotypes to HCC has not been revealed to date. The study aimed to evaluate the contribution of MMP-7 promoter A-181G (rs11568818) and C-153T (rs11568819) genotypes on the risk of HCC in Taiwan, where HCC incidence is extremely high compared to worldwide data. MATERIALS AND METHODS: In this case-control study, MMP-7 genotypes and their association with cigarette smoking and alcohol drinking habits were determined in 298 HCC patients and 889 healthy subjects by a typical polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) methodology. RESULTS: Ever smokers and alcohol drinkers were represented with higher percentages in the case group compared to the control group. MMP-7 rs11568818 genotypes were not found differentially distributed in case and control groups (p for trend=0.5246). People of the analyzed cohort of the present study were all of CC genotypes at their rs11568819 polymorphic sites, without any CT or TT genotypes. As for gene-lifestyle interactions, people with variant genotypes at MMP-7 rs11568818 had the same odds for HCC development compared to the wild-type AA genotype, no matter whether the subjects belonged to the smoker, non-smoker alcohol drinker, or non-drinker groups. CONCLUSION: MMP-7 variant genotypes did not present any significance towards being a marker for HCC risk in Taiwanese.

Role of Matrix Metallopeptidase-2 Genotypes in Taiwanese Patients With Colorectal Cancer.

BACKGROUND/AIM: Matrix metalloproteinase-2 (MMP2) has been reported to plays a critical role in the metastatic behaviors of cancer via regulation of the extracellular matrix. However, its genotypes have seldom been examined in colorectal cancer (CRC). We examined the role of MMP2 promoter -1306 (rs243865) and -735 (rs2285053) genotypes in colorectal cancer (CRC). MATERIALS AND METHODS: Genotypes of MMP2 were determined by typical polymerase chain reaction-restriction fragment length polymorphism methodology in 362 CRC cases and 362 age-, sex- and behavior-matched controls. RESULTS: The genotypic analysis showed that MMP2 -1306 CT and TT genotypes were significantly associated with an increased CRC risk (odds ratios=1.41 and 3.55, 95% confidence intervals=1.02-1.96 and 1.75-7.19, and p=0.0482 and p=0.0004, respectively). The allelic frequency analysis showed that the T allele for MMP2 -1306 increased CRC risk (odds ratio=1.71, 95% confidence interval=1.32-2.23, p=4.89×105). Stratification analysis showed that MMP2 -1306 genotypes were specifically associated with alcohol drinking, and metastatic status among patients with CRC. There was no association with MMP2 -735. CONCLUSION: The MMP2 -1306 genotype serves as a novel predictive marker for CRC risk among Taiwanese, and patients who have a tendency to undergo metastasis.

Contribution of Cyclin-dependent Kinase Inhibitor 1B Genotypes to Childhood Leukemia Risk.

BACKGROUND/AIM: Although genetic differences in cell-cycle control genes have been associated with cancer risk, to our knowledge, no report has specifically examined the role of gene variants in childhood acute lymphoblastic leukemia (ALL). Cyclin-dependent kinase inhibitor 1B (CDKN1B; also known as p27/KIP1) is a cell-cycle regulating gene. This study aimed at investigating the association between CDKN1B genotypes and childhood ALL risk. MATERIALS AND METHODS: In 266 childhood ALL cases and 266 healthy controls, the CDKN1B rs34330 and 2066827 polymorphisms were genotyped, and the association of CDKN1B genotypes with childhood ALL risk were analyzed. RESULTS: The genotypes of CDKN1B rs34330 and 2066827 were similarly distributed between the control and case groups (p for trend=0.8718 and 0.4030, respectively). The allelic frequency also exhibited no statistical difference (p=1.0000 and 0.6666, respectively). There was no significant interaction between CDKN1B genotypes and age or sex. CONCLUSION: CDKN1B genotypes were not found to be minor contributors to childhood ALL susceptibility in Taiwan.

Contribution of 5-Methyltetrahydrofolate-Homocysteine Methyltransferase Reductase Genotypes to Colorectal Cancer in Taiwan.

BACKGROUND/AIM: 5-methyltetrahydrofolate-homocysteine methyltransferase reductase (MTRR) is responsible for folate metabolism, and we aimed to investigate its genetic role in colorectal cancer (CRC) among Taiwanese. MATERIALS AND METHODS: A total of 362 cases and 362 controls were recruited and their MTRR rs1801394 (A66G) and rs1532268 (C524T) genotypes were examined. The behavioral factors and clinicalpathological factors were also analyzed. RESULTS: MTRR rs1801394 genotypes were associated with CRC risk (p for trend=0.0087). In detail, G/G genotype was associated with lower risk (p=0.0049, OR=0.39, 95%CI=0.20-0.76). As for allelic frequency analysis, G allele was also associated with decreased CRC risk (p=0.0026, OR=0.68, 95%CI=0.53-0.88). There was no significant association as for MTRR rs1532268. Among non-smokers and non-alcohol drinkers, those with G/G genotype were at 0.38- and 0.46-fold odds of having CRC. There were no significant protective effects among smokers or alcohol drinkers. CONCLUSION: MTRR rs1801394 GG genotype can be a protective marker for CRC risk in Taiwan.

Association of Matrix Metallopeptidase-2 Genotypes With Risk of Gastric Cancer in Taiwan.

BACKGROUND/AIM: Matrix metalloproteinase-2 (MMP-2) plays a critical role in the regulation of the extracellular matrix; however, its genotypes have seldom been examined in gastric cancer (GC). This study aimed to investigate the contribution of MMP-2 promoter -1306 (rs243865) and -735 (rs2285053) genotypes to GC risk in a cohort of Taiwanese individuals. MATERIALS AND METHODS: This study included 121 GC cases and 363 age- and sex-matched controls. The genotypes of MMP-2 were determined by typical polymerase chain reaction-restriction fragment length polymorphism. RESULTS: The genotypic and allelic frequency analysis showed that MMP-2 rs243865 variant genotypes decreased the risk of GC. Stratification analysis showed that MMP-2 rs243865 genotypes associate with smoking, alcohol drinking, and Helicobacter pylori infection status to confer personal susceptibility to GC. There is no such association for MMP-2 rs2285053 genotype with GC risk. CONCLUSION: The MMP-2 rs243865 genotypes may serve as a novel predictive marker for GC personal susceptibility among Taiwanese.

Novel Contribution of Long Non-coding RNA MEG3 Genotype to Prediction of Childhood Leukemia Risk.

BACKGROUND/AIM: Acute lymphoblastic leukemia (ALL) is frequent among children. Few studies have researched the relationship between maternally expressed gene 3 (MEG3) and cancer risk. We hypothesized long non-coding RNA MEG3 polymorphisms might influence the risk of childhood ALL. MATERIALS AND METHODS: In a total of 266 patients with childhood ALL and 266 healthy controls, genotypes of MEG3 rs7158663, rs3087918, rs11160608 and rs4081134 single nucleotide polymorphisms were investigated for their associations with childhood ALL. RESULTS: MEG3 rs7158663 AG and AA genotypes were significantly associated with ALL [odds ratio=1.61 (95% confidence interval=1.12-2.31) and 2.21 (1.16-4.22), respectively]. The A allele also exhibited a statistical association with higher risk of ALL (p=0.0015). There was no positive association as for rs3087918, rs11160608 or rs4081134. Interestingly, a significant interaction between MEG3 rs7158663 and age (≥3.5 years) and gender (male) was found. CONCLUSION: MEG3 rs7158663 AG/AA genotypes were associated with higher susceptibility to childhood ALL. These novel findings should be validated in larger populations and different ethnicities.

Significant Association of CCND1 Genotypes With Susceptibility to Childhood Acute Lymphoblastic Leukemia.

BACKGROUND/AIM: This study investigated whether genetic variations in cyclin D1 (CCND1) are associated with susceptibility to childhood acute lymphoblastic leukemia (ALL). MATERIALS AND METHODS: A total of 266 childhood ALL cases and 266 healthy controls were genotyped for CCND1 rs9344 and rs678653. RESULTS: There was a significant difference in the genotypic distribution of rs9344 between childhood ALL patients and healthy controls (p=0.0077). Compared to the AA genotype, AG and GG genotypes were associated with significantly decreased risks of childhood ALL with odds ratio (OR) of 0.65 [95% confidence interval (CI)=0.44-0.94, p=0.0234] and 0.45 (95%CI=0.26-0.78, p=0.0040), respectively. Supporting this, allelic frequency distributions between childhood ALL patients and controls was significantly different (OR=0.68, 95%CI=0.53-0.88, p=0.0025). There was no significant difference in the genotypic and allelic distributions of rs678653 between cases and controls. CONCLUSION: CCND1 rs9344, but not rs678653, may serve as a predictive marker of susceptibility for childhood ALL.

The Association of MMP9 Promoter Rs3918242 Genotype With Gastric Cancer.

BACKGROUND/AIM: Matrix metalloproteinase 9 (MMP9) is highly expressed in gastric cancer but the role of MMP9 is unclear. This study aimed at revealing the association of MMP9 promoter rs3918242 genotypes with gastric cancer risk. MATERIALS AND METHODS: MMP9 rs3918242 genotypes of 121 patients with gastric cancer and 363 healthy individuals were examined by polymerase chain reaction-restriction fragment length polymorphism methodology using serum samples. RESULTS: MMP9 rs3918242 TT genotype carriers had an elevated gastric cancer risk compared to wild-type CC carriers (odds ratio=3.92, 95% confidence interval=1.28-11.99; p=0.0103). Patients with CT/TT genotypes were at higher risk of metastasis (p=0.0178) than those with CC. No correlation was found between MMP9 rs3918242 genotype and gastric cancer risk with smoking or alcohol behavior, nor Helicobacter pylori infection. No correlation was observed for MMP9 rs3918242 genotypic distributions with age, gender, or body mass index. CONCLUSION: Carrying a T allele for MMP9 rs3918242 may be predictive for higher gastric cancer risk, and as a predictor for higher risk of metastasis.

Significant Associations of lncRNA H19 Genotypes with Susceptibility to Childhood Leukemia in Taiwan.

The purpose of our study was to investigate whether genetic variations in lncRNA H19 were associated with susceptibility to childhood leukemia. Two hundred and sixty-six childhood leukemia patients and 266 healthy controls were enrolled in Taiwan, and two single nucleotide polymorphisms (SNPs), rs2839698 and rs217727, in H19 were genotyped and analyzed. There was a significant difference in the genotypic distribution of rs2839698 between patients and healthy controls (p = 0.0277). Compared to the wild-type CC genotype, the heterozygous variant CT and homozygous variant TT genotypes were associated with significantly increased risks of childhood leukemia with an adjusted odd ratio (OR) of 1.46 (95% confidence interval (CI), 1.08-2.14, p = 0.0429) and 1.94 (95%CI, 1.15-3.31, p = 0.0169), respectively (pfor tread = 0.0277). The difference in allelic frequencies between childhood leukemia patients and controls was also significant (T versus C, adjusted OR = 1.53, 95%CI, 1.13-1.79, p = 0.0077). There were no significant differences in the genotypic and allelic distributions of rs217727 between cases and controls. Interestingly, the average level of H19 rs2839698 was statistically significantly higher for patients with CT and TT genotypes than from those with the CC genotype (p < 0.0001). Our results indicate that H19 SNP rs2839698, but not rs217727, may serve as a novel susceptibility marker for childhood leukemia.

MiR-196a-2 Genotypes Determine the Susceptibility and Early Onset of Childhood Acute Lymphoblastic Leukemia.

BACKGROUND/AIM: The roles of microRNAs (miRNAs) in tumorigenesis have attracted a lot of attention. The current study aimed at examining the association of the miR-196a-2 rs11614913 genotypes with susceptibility to childhood acute lymphoblastic leukemia (ALL) in Taiwan. MATERIALS AND METHODS: This case-control investigation recruited 266 patients with childhood ALL and 266 healthy controls, and the miR-196a-2 rs11614913 genotypes of each participant were examined via the polymerase chain reaction-restriction fragment length polymorphism methodology. RESULTS: The frequency of miR-196a-2 C allele in controls was 0.440 compared with 0.423 in ALL patients. In addition, there was no significant association between CT or CC genotypes with susceptibility to childhood ALL (OR=0.89 and 0.89, 95%CI=0.60-1.30 and 0.54-1.45, p=0.5427 and 0.6302). Furthermore, the frequencies of miR-196a-2 polymorphisms were not associated with age, gender and clinical outcomes in ALL cases. CONCLUSION: The miR-19a-2 genotypes are not associated with susceptibility to childhood ALL in Taiwan.

Association of Adiponectin Genotypes With Colorectal Cancer Susceptibility in Taiwan.

AIM: To investigate the association between adiponectin (ADIPOQ) genotypes and colorectal cancer (CRC) risk among Taiwanese. MATERIALS AND METHODS: Polymerase chain reaction-restriction fragment length polymorphism was adopted to identify ADIPOQ rs266729, rs2241766 and rs1501299 genotypes among 362 CRC patients and 362 healthy controls. RESULTS: ADIPOQ rs266729 GG genotype (p=0.0075) and G allele (p=0.0061) are associated with a significantly increased CRC risk. There is no differential distribution of rs2241766 and rs1501299 genotypes. As for the gene-lifestyle interaction, there are obvious joint effects of rs266729 genotype on the CRC risk among non-smoker, non-alcohol drinker, while not on smoker or non-drinker subgroups. No significant correlation was observed between rs266729 genotypic distributions and age, gender, tumor size, location or metastasis status. Interestingly, a correlation of rs266729 genotype and larger BMI on CRC risk was found. CONCLUSION: G allele at ADIPOQ rs266729 may serve as a determiner for CRC risk, especially for those with BMI ≥24.

Significant Association Between the MiR146a Genotypes and Susceptibility to Childhood Acute Lymphoblastic Leukemia in Taiwan.

BACKGROUND/AIM: Mounting evidence has shown that miRNAs play a critical role in the regulation of hematopoiesis of cell proliferation and apoptosis as well as in tumorigenesis. The miR146a rs2910164 polymorphism, which is closely responsive for its expression, has been reported to associate with the risk of several solid cancers. The study aimed at examining the association of the it with susceptibility to childhood acute lymphoblastic leukemia (ALL) in Taiwan. MATERIALS AND METHODS: We recruited 266 patients with childhood ALL and 266 healthy controls, and rs2910164 genotypes were determined by the polymerase chain reaction-restriction fragment length polymorphism methodology. RESULTS: The allele G was associated with decreased childhood ALL risk (OR=0.66, 95%CI=0.52-0.85, p=0.0011). Consistently, the GG genotype was associated with a decreased susceptibility (OR=0.40, 95%CI=0.23-0.67, p=0.0004). Patients with CG and GG genotypes were of earlier onset than those with CC genotype (p=0.0255 and p=0.0001). CONCLUSION: MiR146a rs2910164 G allele serves as a protective marker for childhood ALL in Taiwan.

Association of Matrix Metalloproteinase-9 rs3918242 Promoter Genotypes With Colorectal Cancer Risk.

BACKGROUND/AIM: 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. MATERIALS AND METHODS: 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. RESULTS: 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. CONCLUSION: MMP-9 rs3918242 genotypes may interact with BMI to serve as a predictor for higher CRC risk, and independently as a predictor for metastasis.

HOGG1 rs1052133 Genotypes and Risk of Childhood Acute Lymphoblastic Leukemia in a Taiwanese Population.

BACKGROUND/AIM: Cells suffer from oxidative DNA damage which leads to the accumulation of 8-oxoguanine (8-oxoG) adducts in our genome that can become carcinogenic. The human 8-oxoG DNA glycosylase 1 (hOGG1) plays a central role in repairing these 8-oxoGs via the base excision repair pathway. Mounting evidence has suggested that hOGG1 polymorphisms may affect the activity of hOGG1 and serve as genomic markers for the prediction of personal susceptibility to several cancers. To determine whether the commonly examined hOGG1 rs1052133 (Ser326Cys) polymorphism is associated with the risk of childhood acute lymphoblastic leukemia (ALL) among Taiwanese children, we genotyped the hOGG1 rs1052133 (Ser326Cys) in 266 cases and 266 controls. RESULTS: The distributions of the GG, CG and CC genotypes at the hOGG1 rs1052133 were 49.2, 39.1 and 11.7% in the control group and 48.1, 36.1 and 15.8% in the case group (p=0.3656). The combined genotypes CG+CC were not associated with increased risk of childhood ALL (odds ratio [OR]=1.05, 95% confidence interval [CI]=0.74-1.47, p=0.7947). CONCLUSION: The hOGG1 rs1052133 polymorphism is not associated with susceptibility to childhood ALL in the Taiwanese population.

Association of Matrix Metallopeptidase-2 Promoter Polymorphisms With the Risk of Childhood Leukemia.

BACKGROUND/AIM: The association of matrix metalloproteinase-2 (MMP-2) genotypes with adult leukemia has been reported only once, but never for childhood leukemia. This study aimed to determine the role of MMP-2 promoter -1306 (rs243865) and -735 (rs2285053) genotypes in childhood leukemia risk. MATERIALS AND METHODS: This case-control study included 266 patients and 266 age- and gender-matched healthy controls. The polymorphic sites of MMP-2 were genotyped by typical polymerase chain reaction-restriction fragment length polymorphism. RESULTS: The CC, CT and TT of rs243865 genotype were 75.2, 23.7 and 1.1% in the case group and 69.2, 28.9 and 1.9% in the control group, respectively. The CT and TT genotypes caused a 0.75- and 0.55-fold increase in the risk of childhood leukemia, respectively. There was no differential distribution of rs2285053 genotypes. Allelic frequency analysis showed that the T allele of MMP-2 promoter -1306 and -735 conferred lower susceptibility than the C allele. CONCLUSION: The MMP-2 promoter genotypes play a minor role in determining personal susceptibility to childhood leukemia among the Taiwanese.