• Asian Pacific Journal of Cancer Prevention
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• v.15 no.12
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• pp.4843-4846
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• 2014

Background: Acute lymphoblastic leukemia (ALL) is most common in childhood. Inhibin (a non-steroidal glycoprotein hormone of gonadal origin) can be used as marker of fertility. The current study was conducted to evaluate inhibin levels in ALL patients and to estimate its correlation with some antioxidants in these in comparison with control subjects. Materials and Methods: This study was conducted on sixty patients with ALL and thirty children as controls. Fasting blood samples were taken from each subject and analyzed for haemoglobin, serum protein, vitamin E and C, in addition to glutathione and inhibin. Results: The results of the study showed highly significant decreases (p<0.001) in haemoglobin, glutathione and inhibin levels with significant decreases (p<0.05) in serum protein and vitamin E levels for patients group in comparison with controls while there was no significant differences in vitamin C. Moreover, there were significant correlations between inhibin levels and serum protein, glutathione and both vitamins (E and C) in the ALL patient group (r= 0.81, 0.80, 0.77 and 0.69, respectively). Conclusions: The present results indicated infertility in patients with ALL demonstrated by low inhibin level as a consequence of abnormality in anti-oxidative metabolism due to the cancer process. So, it can be suggested the need for routine measurement of inhibin for leukemic patients to estimate the action of hormones of gonadal origin.

• Asian Pacific Journal of Cancer Prevention
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• v.17 no.11
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• pp.4985-4989
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• 2016

Long non-coding RNAs (lncRNAs) are a novel class of non-protein coding RNAs that are involved in a wide variety of biological processes. There are limited data regarding the impact of lnc-LAMC2-1:1 rs2147578 as well as CASC8 rs10505477 T>C polymorphisms on cancer development. Here we examined for the first time whether rs2147578 and rs10505477 polymorphisms are associated with childhood acute lymphoblastic leukemia (ALL) in a total of 110 cases and 120 healthy controls. Genotyping was achieved by the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method. The rs2147578 variant increased the risk of ALL in codominant (OR=4.33, 95%CI=2.00-9.37, p<0.0001, CG vs CC, and OR=5.81, 95%CI=2.30-14.69, p=0.0002, GG vs CC), dominant (OR=4.63, 95%CI=2.18-9.86, p<0.0001, CG+GG vs CC), overdominant (OR=1.74, 95%CI=1.02-2.97, p=0.0444, CG vs CC+GG) and allele (OR=1.91, 95%CI=1.32-2.77, p=0.0008, G vs C) inheritance models tested. No significant association was found between the CASC8 rs10505477 T>C variant and risk of childhood ALL. In conclusion, the present study revealed that the lnc-LAMC2-1:1 rs2147578 polymorphism may be a risk factor for developing childhood ALL. Further studies with larger sample sizes with different ethnicities are now required to confirm our findings.

• Asian Pacific Journal of Cancer Prevention
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• v.16 no.11
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• pp.4727-4732
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• 2015

Background: Folylpolyglutamate synthetase (FPGS), an important enzyme in the folate metabolic pathway, plays a central role in intracellular accumulation of folate and antifolate in several mammalian cell types. Loss of FPGS activity results in decreased cellular levels of antifolates and consequently to polyglutamatable antifolates in acute lymphoblastic leukemia (ALL). Materials and Methods: During May 1997 and December 2003, 134 children diagnosed with ALL were recruited from one hospital in Thailand. We performed a mutation analysis in the coding regions of the FPGS gene and the association between single nucleotide polymorphisms (SNPs) within FPGS in a case-control sample of childhood ALL patients. Mutation screening was conducted by polymerase chain reaction-single strand conformation polymorphism (PCR-SSCP) and subsequently with direct sequencing (n=72). Association analysis between common FPGS variants and ALL risk was done in 98 childhood ALL cases and 95 healthy volunteers recruited as controls. Results: Seven SNPs in the FPGS coding region were identified by mutation analysis, 3 of which (IVS13+55C>T, g.1297T>G, and g.1508C>T) were recognized as novel SNPs. Association analysis revealed 3 of 6 SNPs to confer significant increase in ALL risk these being rs7039798 (p=0.014, OR=2.14), rs1544105 (p=0.010, OR= 2.24), and rs10106 (p=0.026, OR=1.99). Conclusions: These findings suggested that common genetic polymorphisms in the FPGS coding region including rs7039789, rs1544105, and rs10106 are significantly associated with increased ALL risk in Thai children.

• Asian Pacific Journal of Cancer Prevention
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• v.14 no.3
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• pp.1629-1633
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• 2013

Background: Gene set analysis (GSA) incorporates biological with statistical knowledge to identify gene sets which are differentially expressed that between two or more phenotypes. Materials and Methods: In this paper gene sets differentially expressed between acute lymphoblastic leukaemia (ALL) with BCR-ABL and those with no observed cytogenetic abnormalities were determined by GSA methods. The BCR-ABL is an abnormal gene found in some people with ALL. Results: The results of two GSAs showed that the Category test identified 30 gene sets differentially expressed between two phenotypes, while the Hotelling's $T^2$ could discover just 19 gene sets. On the other hand, assessment of common genes among significant gene sets showed that there were high agreement between the results of GSA and the findings of biologists. In addition, the performance of these methods was compared by simulated and ALL data. Conclusions: The results on simulated data indicated decrease in the type I error rate and increase the power in multivariate (Hotelling's $T^2$) test as increasing the correlation between gene pairs in contrast to the univariate (Category) test.

• Asian Pacific Journal of Cancer Prevention
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• v.16 no.17
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• pp.7613-7618
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• 2015

Childhood acute lymphoblastic leukemia (ALL) is one of the most common hematologic malignancies which accounts for one fourth of all childhood cancer cases. Exposure to environmental factors around the time of conception or pregnancy can increase the risk of ALL in the offspring. This study aimed to evaluate the influence of prenatal and postnatal exposure to high voltage power lines on the incidence of childhood ALL. It also examines the role of various factors such as environmental factors and alpha-amylase as a marker in the development of leukemia.This cross-sectional case control study was carried out on 22 cases and 100 controls who born and lived in low socioeconomic families in Tehran and were hospitalized for therapeutic purposes in different hospitals ofrom 2013-2014. With regard to the underlying risk factors; familial history and parental factors were detected as risk factors of ALL but in this age, socioeonomic and zonal matched case control study, prenatal and childhood exposure to high voltage power lines was considered as the most important environmental risk factor (p=0.006, OR=3.651, CI 95% 1.692-7.878). As the population study was from low socioeconomic state, use of mobiles, computers and microwaves was negligible. Moreover prenatal and postnatal exposure to all indoor electrically charged objects were not detected as significant environmental factors in the present study. This work defined the risk of environmental especially continuous pre and postnatal exposure to high voltage power lines and living in pollutant regions through the parents or children as well as the previously described risk factors of ALL for the first time in low socioeconomic status Iranian population.

• Asian Pacific Journal of Cancer Prevention
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• v.13 no.7
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• pp.3461-3464
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• 2012

Methotrexate (MTX) is an important drug for the treatment of childhood acute lymphoblastic leukemia (ALL). However, related toxicity occurs in many organs which may cause interruption of treatment, morbidity, and mortality. Single nucleotide polymorphisms (SNPs) of dihydrofolate reductase (DHFR) and gamma glutamyl hydrolase (GGH) are known to alter their enzymatic activity and thus affect the metabolism of MTX and influence the effectiveness. Therefore, we hypothesized that genetic variations of DHFR and GGH genes may influence the risk of toxicity after high dose MTX. The study population comprised of 105 children with ALL who were treated according to the modified St Jude Total XV protocol. The patients received 2.5 or $5g/m^2$ of MTX for 5 doses during the consolidation phase. Genotyping of DHFR 829C>T and GGH-401C>T was performed using a polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). The GGH-401CT and TT genotypes were associated with increased risk of leukopenia and thrombocytopenia after high dose MTX (OR 2.97, 95%CI; 1.24-7.13 and OR 4.02, 95%CI; 1.58-10.26). DHFR 829C>T was not associated with toxicity. In conclusion, the GGH-401CT and TT genotypes were found to increase the risk of severe leukopenia and thrombocytopenia after exposure to high dose MTX for childhood ALL therapy.

• Asian Pacific Journal of Cancer Prevention
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• v.17 no.4
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• pp.2307-2309
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• 2016

Background: Acute lymphoblastic leukemia (ALL) is a malignant disease in which early lymphoid precursors proliferate and replace the normal hematopoiesis. It has distinctive clinical and biological features. In respect to adult ALL, available data from Pakistan are limited. Therefore we reviewed the demographical and clinicohematological profiles along with FAB stratification of adult patients with ALL presented at our hospital. Materials and Methods: In this cross sectional study, 51 adults (${\geq}15years$) patients with ALL were enrolled from January 2010 to December 2014. Results: The mean age was $23.8{\pm}12.9years$ with the median age of 18.0 years. The male to female ratio was 2:1. The major complaints were fever (60.7%), generalized weakness (47.0%), overt bleeding (19.6%) and weight loss (13.7%). Physical examination revealed lymphodenopathy as a predominant finding detected in 43.1% followed by splenomegaly and hepatomegaly in 23.5% and 21.5%, respectively. The mean hemoglobin level was $9.0{\pm}2.75g/dl$ with a mean MCV of $82.2{\pm}15.4fl$, a mean total leukocyte count of $31.1{\pm}64.0{\times}10^9/l$, a mean ANC of $2.1{\pm}3.0{\times}10^9/l$ and a mean platelet count of $71.7{\pm}85.7{\times}10^9/l$. According to FAB classification, 47.1% were L1 type, 45.1% L2 and 7.8% L3 variant. Conclusions: Clinico-pathological features appeared comparable to published data. Febrile illness associated with lymphodenopathy was the commonest presentation. FAB classification revealed a predominance of ALL-L1 variant in Pakistani adult patients with ALL.

• Asian Pacific Journal of Cancer Prevention
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• v.13 no.10
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• pp.5251-5255
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• 2012

Background and Aim: Although the functional consequences of MDR-1 polymorphisms have been the subject of numerous studies, to the best to our knowledge, associations with clinical side effects of anticancer drugs have yet to be assessed. Our aim was to clarify any role of the C3435T polymorphism of the MDR1 gene in oral mucositis and its relation with elevated reactive oxygen species (ROS) levels, in children with acute lymphoblastic leukemia (ALL). Materials and Methods: The distribution of the MDR-1 C3435T polymorphism in 47 patients with ALL was determined by RFLP and compared with that of 68 healthy controls. Results: There were no association in distribution of genotypes of MDR-1 C3435T polymorphism and the risk of ALL. Oral mucositis were detected in 78.7% (n=37) of the patients and significantly related to the MDR-1 CT genotype (p=0.042), as confirmed by logistic regression analysis. Conclusion: Our preliminary data suggest that children carrying the CT genotype are more prone to develop oral mucositis, which might mean that the heterozygous genotype leads to accumulation of more reactive oxygen species. Since a limited number of patients was investigated, further studies are needed to confirm these findings.

• Asian Pacific Journal of Cancer Prevention
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• v.14 no.2
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• pp.1127-1130
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• 2013

Background: The standard national protocol for treatment of acute lymphoblastic leukemia (ALL) in children was implemented in 2006. A systematic evaluation of the treatment outcome is needed. This study examined the relapse-free survival among childhood ALL cases treated with this protocol and related factors. Materials and Methods: A descriptive study was conducted in children aged between 0-15 years, newly diagnosed with ALL between March 2006 and March 2011 at Srinagarind Hospital, Department of Pediatrics, Faculty of Medicine, Khon Kaen University. The patients were treated on the basis of stratified risk as per the Thai national protocol. Data were compiled from the hospital records. The Kaplan-Meier method was used to describe relapse-free survival and the Cox proportional hazard model to investigate the associated factors. Results: Of the 103 children recruited, 86 (83.5%) achieved complete remission. The total follow-up time was 3132.5 person-months. Eighteen (20.9%) relapsed. The incidence density was 0.6 per 100 person-months (95%CI: 0.4, 0.9). The respective relapse-free rates at 1, 3 and 5 years were 93.0% (95%CI: 85.1, 96.8), 84.5% (95%CI: 74.0, 90.9) and 64.1% (95%CI: 45.6, 77.8). A factor associated with the relapse-free rate was age under 1 year (HR=6.0; 95%CI: 1.1, 33.8). Conclusions: The rate of being relapse-free in ALL children treated under the Thai national protocol at Srinagarind Hospital was better than with former protocols; however, it is still not as good as in developed countries. Further review of the treatment approach of ALL is needed.

• Clinical and Experimental Pediatrics
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• v.50 no.7
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• pp.601-605
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• 2007

The cure rate of acute lymphoblastic leukemia (ALL) in children dramatically improved over past 5 decades from zero to about 80%. The main cause of improvement is owing to the development of chemotherapy by multicenter clinical trial of large study groups with the understanding of leukemia biology. Recently, pediatric ALL protocols were applied to the treatment of adolescent and even adult ALL patients. For nearly 30 years, clinical factors have been used to risk-stratify therapy for children with ALL, so that the most intensive therapies are reserved for those patients at the highest risk of relapse. The risk groups of ALL are divided as standard- (low- plus intermediate-), high- and very high-risk group according to the prognostic factors, and treatment results improved by this risk based treatment. The factors used to risk-stratify therapy include age, gender, presenting leukocyte count, immunophenotype, cytogenetic aberrations including ploidy and translocations, and initial response after 1 to 2 weeks of therapy. But treatment efficacy is the most important determinant and can abolish the clinical significance of most, if at all, prognostic factors. Today, in the era of intensive, multiagent regimens, there is increasing evidence that we have reached the limits of prognostic significance of currently applied clinical risk factors in childhood ALL. As the cure rate of ALL is about 80%, introducing new prognostic factors such as new molecular prognostic markers, new methods of assessment about minimal residual disease, and pharmacogenetic study, with the development of stem cell transplantation and molecular targeted therapy are needed to cure residual 20% of childhood ALL patients without short and long term complications.