ABSTRACT
BACKGROUND: MiR-34b/c takes an important role in various aspects of carcinogenesis. Notably, pri miR34b/c (rs4938723) T>C polymorphism has been identified as a significant biomarker in various kinds of cancer. The objective of this study was to explore whether pri-miR34b/c rs4938723) T>C was associated with breast cancer susceptibility. Moreover, the association of pri-miR34b/c (rs4938723) T>C and clinicopathologic data, including survival outcomes, were studied in Thai breast cancer patients. METHODS: DNA extracted from the blood of 100 Thai female breast cancer patients and 100 Thai healthy women were investigated for pri-miR34b/c (rs4938723) T>C polymorphism using polymerase chain reaction-restriction fragment-length polymorphism (PCR-RFLP). RESULTS: There was no statistically significant difference between the frequency of pri miR34b/c (rs4938723) T>C genotype between Thai breast cancer patients and normal subjects. This study showed that there is no association between pri-miR34b/c (rs4938723) genotypes and breast cancer susceptibility, clinicopathologic parameters, and survival time. However, age greater than 50 and histologic grade III were the prognostic factors affecting survival in breast cancer patients (p=0.017, p=0.010, respectively). CONCLUSION: The pri-miR34b/c (rs4938723) genotypes had no association with cancer susceptibility and clinicopathologic parameters in Thai breast cancer patients. Patients with older age and patients with higher histologic grade, but not the pri miR34b/c (rs4938723) genotype, affected survival time among breast cancer patients.
Subject(s)
Biomarkers, Tumor , Breast Neoplasms , Genetic Predisposition to Disease , Genotype , MicroRNAs , Humans , Female , MicroRNAs/genetics , Breast Neoplasms/genetics , Breast Neoplasms/pathology , Breast Neoplasms/mortality , Middle Aged , Prognosis , Case-Control Studies , Biomarkers, Tumor/genetics , Survival Rate , Polymorphism, Single Nucleotide , Adult , Thailand/epidemiology , Follow-Up Studies , Aged , Polymorphism, Restriction Fragment LengthABSTRACT
BACKGROUND: MiR27a plays an important role in carcinogenesis, cell proliferation, apoptosis, invasion, migration and angiogenesis. Several studies have identified an important role of pre-miR27a (rs895819) A>G polymorphism in several types of cancer. This research aims to investigate the association of pre-miR27a (rs895819) A>G and breast cancer susceptibility, clinicopathological data and survival. Blood DNA samples of 143 Thai breast cancer patients and 100 healthy Thai women were studied for pre-miR27a (rs895819) A>G polymorphism using polymerase chain reaction-restriction fragment-length polymorphism (PCR-RFLP). RESULTS: The results revealed that the frequency of pre-miR27a (rs895819) A>G genotypes was not statistically significant different between breast cancer patient and normal control subjects. The rs895819 A>G genotype was significantly associated with clinicopathological parameter of grade III differentiation (P = 0.006), progesterone receptor (P = 0.011) and triple negative (P = 0.031) in breast cancer patients, but not with breast cancer susceptibility. CONCLUSION: The pre-miR27a (rs895819) A>G genotype was significantly associated with poorly differentiated, progesterone receptor and triple-negative in breast cancer patients. Therefore, pre-miR27a (rs895819) A>G may be used as a biomarker for poor prognosis.
Subject(s)
Breast Neoplasms , MicroRNAs , Triple Negative Breast Neoplasms , Female , Humans , Breast Neoplasms/genetics , Case-Control Studies , Genetic Predisposition to Disease , Genotype , MicroRNAs/genetics , Polymorphism, Single Nucleotide , Receptors, Progesterone/genetics , Southeast Asian PeopleABSTRACT
Objectives: This study assessed associations of the miR196a2 (rs11614913) T>C polymorphism withsusceptibility to childhood acute lymphoblastic leukemia (ALL) and clinical outcomes. Materials and Methods: Blood DNA samples from 104 childhood ALL patients and 180 healthy children were studied for the miR-196a2 (rs11614913) polymorphism using a polymerase chain reaction-restriction fragment-length polymorphism (PCR-RFLP) approach. Results: The frequency of the miR-196a2 (rs11614913) T allele in controls was 0.51 compared with 0.33 in ALL cases. In this study, CC, TC heterozygote and CC/TC genotypes were significantly associated with increase childhood ALL susceptibility compared with the TT wild type (OR =4.321, 95% CI = 2.091-8.930 p=0.000, OR = 2.248, 95% CI =1.103-4.579, p=0.024, OR = 2.921, 95% CI = 1.504-5.673 p=0.001, respectively). However, the miR-196a2 (rs11614913) T>C polymorphism was not associated with demographic data or clinico-pathological data in ALL cases. Conclusion: CC, TC and CC+TC genotypes of miR-196a2 (rs11614913) was significantly associated with increased susceptibility in Thai childhood ALL but not with clinical variables.
ABSTRACT
BACKGROUND: MiRNAs, small non coding RNAs, play a role in the regulation of hematopoiesis, with effects on cell growth, differentiation, and apoptosis. In addition, MiRNAs are thought to play an important role in tumorigenesis. The miR146a G>C polymorphism can lead to alteration of miR146 expression, which appears to be associated with development and progression of several cancers. This study aimed to investigate the association of the miRNA146a (rs2910164) G>C polymorphism and susceptibility to childhood acute lymphoblastic leukemia (ALL) and clinical outcomes. MATERIALS AND METHODS: Totals of 100 childhood ALL patients and 200 healthy children were studied for miR146a polymorphisms using polymerase chain reaction-restriction fragment-length polymorphism (PCR-RFLP). RESULTS: The frequency of the miR146a G allele in controls was 0.40 compared with 0.38 in ALL patients. There was no association between miRNA146a (rs2910164) G>C polymorphism and susceptibility to childhood ALL (OR=1.484, 95%CI=0.712-3.093, p=0.290). Moreover, the frequencies of miR146a (rs2910164) G>C polymorphism were not associated with demographic data and clinical outcomes in ALL cases. CONCLUSIONS: The miRNA146a polymorphism was not significantly associated with susceptibility to Thai childhood ALL or any clinico-pathological variables.
Subject(s)
Biomarkers, Tumor/genetics , MicroRNAs/genetics , Polymorphism, Single Nucleotide/genetics , Precursor Cell Lymphoblastic Leukemia-Lymphoma/genetics , Case-Control Studies , Child , Child, Preschool , Female , Follow-Up Studies , Genetic Predisposition to Disease , Genotype , Humans , Infant , Male , Neoplasm Staging , Polymerase Chain Reaction , Polymorphism, Restriction Fragment Length , Precursor Cell Lymphoblastic Leukemia-Lymphoma/pathology , Prognosis , Retrospective Studies , ThailandABSTRACT
BACKGROUND: MDR1, one of the most important drug-transporter genes, encodes P- glycoprotein (P-gp)-a transporter involved in protecting against xenobiotics and multi-drug resistance. The significance of the genetic background in childhood acute lymphoblastic leukemia (ALL) is not well understood. MATERIALS AND METHODS: To evaluate whether C3435T and C1236T MDR1 polymorphisms are associated with the occurrence and outcome of ALL, 208 children with ALL (median age 5.0 yr) and 101 healthy Thai children were studied by polymerase chain reaction-restriction fragment-length polymorphism (PCR-RFLP) assay. RESULTS: C3435T and C1236T MDR1 polymorphism are significantly associated with the high-risk group (OR=2.6, 95%CI=1.164-5.808; P=0.028 and OR=2.231, 95%CI=1.068-4.659; p=0.047, respectively), indicating that both may be candidates for molecular markers in the high-risk group of ALL.
Subject(s)
Drug Resistance, Multiple/genetics , Haplotypes/genetics , Polymorphism, Genetic/genetics , Precursor Cell Lymphoblastic Leukemia-Lymphoma/genetics , ATP Binding Cassette Transporter, Subfamily B/genetics , Adolescent , Asian People , Case-Control Studies , Child , Child, Preschool , Female , Follow-Up Studies , Genotype , Humans , Immunophenotyping , Male , Neoplasm Staging , Polymerase Chain Reaction , Polymorphism, Restriction Fragment Length , Precursor Cell Lymphoblastic Leukemia-Lymphoma/pathology , Prognosis , Retrospective Studies , Risk FactorsABSTRACT
Glutathione S-transferases (GSTs) are enzymes that involved in bio- transformation by conjugation of electrophillic compounds to glutathione. Polymorphisms within genes that encode GSTs may affect the function of the enzymes. Polymorphisms of GSTP1 at codon 105 residue forms GSTP1 active site for binding of hydrophobic electrophiles, and the Ile-Val substitution affect substrate specific catalytic activity of this enzyme and may associate with susceptibility to malignant human disease, especially acute lymphoblastic leukemia (ALL), which is the most common leukemia in children younger than 15 years old. Genetic polymorphisms within the GSTP1 gene of childhood ALL patients were studied. In addition, the association of genetic polymorphism of GSTP1 and genetic susceptibility of acute lymphoblastic leukemia (ALL) was also determined using Chi-square and Odds ratio. PCR-RFLP was used to study genetic polymorphism of GSTP1 in 100 ALL patients and 100 healthy individuals.The results show that there is no statistically significant association between each genotypes and genetic susceptibility of acute lymphoblastic leukemia (ALL) (OR=0.92, P -value=0.886). Moreover, there is no statistically significant association between each genotypes and demographic data of acute lymphoblastic leukemia (ALL). However, there are 2 cases of ALL with BM relapse show the polymorphic genotypes of GSTP1. It may suggest that GSTP1*V105 may be involved in relapse of ALL.
