<i>GSTP1</i> rs1138272 Polymorphism Affects Prostate Cancer Risk
<i>Background and Objectives</i>: One of the most frequent genetic alterations reported to date in prostate cancer (PC) is aberrant methylation of glutathione transferase P1 (<i>GSTP1</i>). Taking into consideration the involvement of oxidative stress in PC pathogenesis and r...
| Main Authors: | , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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MDPI AG
2020-03-01
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| Series: | Medicina |
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| Online Access: | https://www.mdpi.com/1010-660X/56/3/128 |
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| author | Veljko Santric Milica Djokic Sonja Suvakov Marija Pljesa-Ercegovac Marina Nikitovic Tanja Radic Miodrag Acimovic Vesna Stankovic Uros Bumbasirevic Bogomir Milojevic Uros Babic Zoran Dzamic Tatjana Simic Dejan Dragicevic Ana Savic-Radojevic |
| author_facet | Veljko Santric Milica Djokic Sonja Suvakov Marija Pljesa-Ercegovac Marina Nikitovic Tanja Radic Miodrag Acimovic Vesna Stankovic Uros Bumbasirevic Bogomir Milojevic Uros Babic Zoran Dzamic Tatjana Simic Dejan Dragicevic Ana Savic-Radojevic |
| author_sort | Veljko Santric |
| collection | DOAJ |
| description | <i>Background and Objectives</i>: One of the most frequent genetic alterations reported to date in prostate cancer (PC) is aberrant methylation of glutathione transferase P1 (<i>GSTP1</i>). Taking into consideration the involvement of oxidative stress in PC pathogenesis and recent advances in scientific understanding of the role of <i>GSTP1*</i>Ala114Val rs1138272 polymorphism in carcinogenesis, we hypothesized that this single-nucleotide polymorphism (SNP) influences the risk of PC independently of, or in combination with, other GST polymorphisms, including <i>GSTP1*</i>IIe105Val rs1695 or <i>GSTM1</i> and <i>GSTT1</i> deletion polymorphisms. <i>Materials and Methods</i>: Genotyping was performed in 237 PC cases and in 236 age-matched controls by multiplex polymerase chain reaction (PCR) for deletion of GST polymorphisms and by quantitative PCR for SNPs. <i>Results</i>: We found that carriers of either <i>GSTP1</i>*Val (rs1138272) or <i>GSTP1</i>*Val (rs1695) variant alleles had a PC risk compared to individuals with both referent alleles (OR = 4.93, 95%CI: 2.89−8.40, <i>p</i> < 0.001 and OR = 1.8, 95%CI: 1.19−2.73, <i>p</i> = 0.006, respectively). Additionally, in a haplotype analysis we found that individuals with <i>GSTP1*C</i> haplotype, represented by both variant alleles <i>(GSTP1*Val rs1695 + GSTP1*Val rs1138272)</i>, had a 5.46 times higher risk of PC development compared to individuals with the most frequent haplotype (95%CI = 2.56−11.65, <i>p</i> < 0.001), suggesting a potential role of those variants in PC susceptibility. A regression analysis on the number of risk-associated alleles per individual (<i>GSTM1*active, GSTT1*null, GSTP1*Val rs1695</i> and <i>GSTP1*Val rs1138272</i>) showed a significant increase in the risk of developing PC, from 3.65-fold in carriers of two risk alleles (95%CI = 1.55−8.61, <i>p</i> = 0.003) to an approximately 12-fold increase in carriers of all four risk alleles (95%CI = 3.05−44.93, <i>p</i> < 0.001). <i>Conclusion</i>: Prostate cancer may be influenced by multiple glutathione transferase (GST) polymorphic genes, especially <i>GSTP1</i>, highlighting the role of gene−gene interactions in human susceptibility to this cancer. |
| first_indexed | 2024-03-12T11:13:56Z |
| format | Article |
| id | doaj.art-b05fc5cc4aa64d9293355a5592b943c6 |
| institution | Directory Open Access Journal |
| issn | 1010-660X |
| language | English |
| last_indexed | 2024-03-12T11:13:56Z |
| publishDate | 2020-03-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Medicina |
| spelling | doaj.art-b05fc5cc4aa64d9293355a5592b943c62023-09-02T02:27:27ZengMDPI AGMedicina1010-660X2020-03-0156312810.3390/medicina56030128medicina56030128<i>GSTP1</i> rs1138272 Polymorphism Affects Prostate Cancer RiskVeljko Santric0Milica Djokic1Sonja Suvakov2Marija Pljesa-Ercegovac3Marina Nikitovic4Tanja Radic5Miodrag Acimovic6Vesna Stankovic7Uros Bumbasirevic8Bogomir Milojevic9Uros Babic10Zoran Dzamic11Tatjana Simic12Dejan Dragicevic13Ana Savic-Radojevic14Clinic of Urology, Clinical Center of Serbia, 11000 Belgrade, SerbiaInstitute for Oncology and Radiology of Serbia, 11000 Belgrade, SerbiaInstitute of Medical and Clinical Biochemistry, 11000 Belgrade, SerbiaInstitute of Medical and Clinical Biochemistry, 11000 Belgrade, SerbiaInstitute for Oncology and Radiology of Serbia, 11000 Belgrade, SerbiaInstitute of Medical and Clinical Biochemistry, 11000 Belgrade, SerbiaClinic of Urology, Clinical Center of Serbia, 11000 Belgrade, SerbiaInstitute for Oncology and Radiology of Serbia, 11000 Belgrade, SerbiaClinic of Urology, Clinical Center of Serbia, 11000 Belgrade, SerbiaClinic of Urology, Clinical Center of Serbia, 11000 Belgrade, SerbiaClinic of Urology, Clinical Center of Serbia, 11000 Belgrade, SerbiaClinic of Urology, Clinical Center of Serbia, 11000 Belgrade, SerbiaInstitute of Medical and Clinical Biochemistry, 11000 Belgrade, SerbiaClinic of Urology, Clinical Center of Serbia, 11000 Belgrade, SerbiaInstitute of Medical and Clinical Biochemistry, 11000 Belgrade, Serbia<i>Background and Objectives</i>: One of the most frequent genetic alterations reported to date in prostate cancer (PC) is aberrant methylation of glutathione transferase P1 (<i>GSTP1</i>). Taking into consideration the involvement of oxidative stress in PC pathogenesis and recent advances in scientific understanding of the role of <i>GSTP1*</i>Ala114Val rs1138272 polymorphism in carcinogenesis, we hypothesized that this single-nucleotide polymorphism (SNP) influences the risk of PC independently of, or in combination with, other GST polymorphisms, including <i>GSTP1*</i>IIe105Val rs1695 or <i>GSTM1</i> and <i>GSTT1</i> deletion polymorphisms. <i>Materials and Methods</i>: Genotyping was performed in 237 PC cases and in 236 age-matched controls by multiplex polymerase chain reaction (PCR) for deletion of GST polymorphisms and by quantitative PCR for SNPs. <i>Results</i>: We found that carriers of either <i>GSTP1</i>*Val (rs1138272) or <i>GSTP1</i>*Val (rs1695) variant alleles had a PC risk compared to individuals with both referent alleles (OR = 4.93, 95%CI: 2.89−8.40, <i>p</i> < 0.001 and OR = 1.8, 95%CI: 1.19−2.73, <i>p</i> = 0.006, respectively). Additionally, in a haplotype analysis we found that individuals with <i>GSTP1*C</i> haplotype, represented by both variant alleles <i>(GSTP1*Val rs1695 + GSTP1*Val rs1138272)</i>, had a 5.46 times higher risk of PC development compared to individuals with the most frequent haplotype (95%CI = 2.56−11.65, <i>p</i> < 0.001), suggesting a potential role of those variants in PC susceptibility. A regression analysis on the number of risk-associated alleles per individual (<i>GSTM1*active, GSTT1*null, GSTP1*Val rs1695</i> and <i>GSTP1*Val rs1138272</i>) showed a significant increase in the risk of developing PC, from 3.65-fold in carriers of two risk alleles (95%CI = 1.55−8.61, <i>p</i> = 0.003) to an approximately 12-fold increase in carriers of all four risk alleles (95%CI = 3.05−44.93, <i>p</i> < 0.001). <i>Conclusion</i>: Prostate cancer may be influenced by multiple glutathione transferase (GST) polymorphic genes, especially <i>GSTP1</i>, highlighting the role of gene−gene interactions in human susceptibility to this cancer.https://www.mdpi.com/1010-660X/56/3/128gstp1polymorphismprostate cancerriskhaplotype |
| spellingShingle | Veljko Santric Milica Djokic Sonja Suvakov Marija Pljesa-Ercegovac Marina Nikitovic Tanja Radic Miodrag Acimovic Vesna Stankovic Uros Bumbasirevic Bogomir Milojevic Uros Babic Zoran Dzamic Tatjana Simic Dejan Dragicevic Ana Savic-Radojevic <i>GSTP1</i> rs1138272 Polymorphism Affects Prostate Cancer Risk Medicina gstp1 polymorphism prostate cancer risk haplotype |
| title | <i>GSTP1</i> rs1138272 Polymorphism Affects Prostate Cancer Risk |
| title_full | <i>GSTP1</i> rs1138272 Polymorphism Affects Prostate Cancer Risk |
| title_fullStr | <i>GSTP1</i> rs1138272 Polymorphism Affects Prostate Cancer Risk |
| title_full_unstemmed | <i>GSTP1</i> rs1138272 Polymorphism Affects Prostate Cancer Risk |
| title_short | <i>GSTP1</i> rs1138272 Polymorphism Affects Prostate Cancer Risk |
| title_sort | i gstp1 i rs1138272 polymorphism affects prostate cancer risk |
| topic | gstp1 polymorphism prostate cancer risk haplotype |
| url | https://www.mdpi.com/1010-660X/56/3/128 |
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