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Common polymorphisms in GSTM1, GSTT1, GSTP1, GSTA1 and susceptibility to colorectal cancer in the Central European population

DOI: 10.1186/2047-783x-17-17

Keywords: Colorectal cancer, GSTA1, GSTT1, GSTM1, GSTP1, Polymorphism

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Abstract:

In this study, we investigated associations of polymorphisms in glutathione S-transferases (GSTs) genes, that is GSTA1, GSTT1, GSTM1 and GSTP1, with CRC in a total of 197 cases and 218 controls originating from the Czech Central European population. Polymorphisms were assessed by polymerase chain reaction/restriction fragment length polymorphism-based methods, allele-specific multiplex and allelic discrimination by real-time polymerase chain reaction.None of investigated polymorphisms showed any associations with CRC, with the exception of GSTP1; where the heterozygote genotype Ile105Val was associated with decreased risk of CRC (P?=?0.043).The frequencies observed in our study are in accordance with those from other European Caucasian populations. Based on our studies, examined variability in GST genes is not a major determinant of CRC susceptibility in the Central European population.Colorectal cancer (CRC) represents the third most frequent type of cancer among males and the second most common cancer in females worldwide. Worldwide, every year, more than 1 million individuals will develop colorectal cancer and the disease-specific mortality rate is nearly 33% in the developed world [1], making the disease a substantial health as well as economic burden on society. Sporadic CRC is a typical multifactorial disease arising from maladaptive interaction between genetic background and certain environmental factors, such as diet or lifestyle, however, the exact role of the genetic background to sporadic CRC remains unclear.Glutathione S-transferases (GSTs) represent a superfamily of phase II metabolic enzymes that catalyze the conjugation between glutathione and chemotherapeutic drugs, carcinogens, environmental pollutants, and a broad spectrum of xenobiotics. GSTs are involved in the metabolism of isothiacyanates (ITCs), naturally occurring molecules that were recently shown to inhibit development of tumors in many experimental models [2] and that also induce apoptosis

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