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Title: The risk of childhood acute lymphoblastic leukemia development related with selected genetic polymorphisms in Polish population

Abstract:

Acute lymphoblastic leukemia (ALL) is the common form of pediatric cancer. It has been suggested that polymorphic variations of some metabolically important genes, together with environmental factors, could contribute to the leukaemia development. Presented study has been performed for the purpose of evaluating the role of carcinogen-metabolizing enzymes and folate pathway enzyme genetic polymorphisms in susceptibility to childhood ALL in Polish population. Further aim of the study has been the description of the frequency of selected polymorphisms in Polish healthy children population. The study group included 1000 healthy newborns, selected from the total of Polish population. The results of analogous 3 genotyping for 400 children with ALL recruited by Polish regional oncology centers have been used as well. Results of the present study suggest that neither the presence of GSTT1*0/*0 nor GSTM1*0/*0 genotype of glutathione S-transferase gene has been associated with increased risk of childhood ALL in Polish population. Further results of combined genotype analysis of these two polymorphisms reveal no association with ALL. In the next phase, the effect of GSTP1*B(313A>G) genetic polymorphism of glutathione Stransferase Pi1 gene has been investigated. Observed frequency of GSTP1*B allele has been higher in the cases relative to the controls (p=0,0006;OR=1,54). The prevalence of GSTP1*B homozygotes has been higher in the ALL group as well, however the difference has not attained statistical significance. These findings suggest that GSTP1*B polymorphism may influence the risk of childhood ALL in Polish population, however, further evaluation is necessary. The frequency of NQO1*2(609C>T) and NQO1*3(465C>T) genetic polymorphisms in NAD(P)H:quinone oxidoreductase1 gene did not differ between cases and individuals from general Polish population and revealed no association with ALL. Further experiments have investigated the effect of 677C<T genetic polymorphism of MTHFR gene. Observed frequency of 677T allele as well as 677TT genotype has been higher in the cases corresponding to the controls. Data has revealed that individual homozygous for 677C>T genetic polymorphism had 4-fold increased risk of ALL (p=0,0006;OR=4,09). This results suggest that 677TT genotype is strongly associated with childhood ALL in Polish population.Results of the present study revealed that the distribution of all polymorphic alleles has not differed among separated macro regions of Poland. It seems to be of big significance to continue molecular epidemiological studies investigating the role of polymorphic variants as possible risk factors for cancer development.

Level of degree:

2 - studia doktoranckie

Degree discipline:

onkologia ; hematologia ; pediatria

Degree grantor:

Wydział Lekarski

Promoter:

Jacek J. Pietrzyk

Date issued:

2009

Format:

application/pdf

Identifier:

oai:dl.cm-uj.krakow.pl:938

Call number:

ZB-110923

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Access rights:

tylko w bibliotece

Location of original object:

Biblioteka Medyczna Uniwersytetu Jagiellońskiego - Collegium Medicum

Object collections:

Last modified:

Nov 21, 2019

In our library since:

Nov 21, 2012

Number of object content hits:

9

Number of object content views in PDF format

9

All available object's versions:

http://dl.cm-uj.krakow.pl:8080/publication/938

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Edition name Date
ZB-110923 Nov 21, 2019

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