EPHX1 and ERCC2 polymorphisms are associated with cisplatin-induced nephrotoxicity and prognosis in Thai cancer patients.
Cisplatin is a widely used chemotherapeutic drug for various cancers. One of the common adverse effects of cisplatin is nephrotoxicity including acute kidney injury (AKI) and acute kidney disease (AKD). Single Nucleotide Polymorphisms (SNPs) can be used to identify cancer patients who are susceptibl...
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Public Library of Science (PLoS)
2025-01-01
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| Series: | PLoS ONE |
| Online Access: | https://doi.org/10.1371/journal.pone.0324699 |
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| author | Saad Ahmed Jakris Eu-Ahsunthornwattana Thanaporn Thamrongjirapat Aruchalean Taweewongsounton Yutthana Rittavee Nintita Sripaiboonkit Thokanit Montien Ngodngamthaweesuk Pitichote Hiranyatheb Thanyanan Reungwetwattana Nuttapong Ngamphaiboon Natini Jinawath |
| author_facet | Saad Ahmed Jakris Eu-Ahsunthornwattana Thanaporn Thamrongjirapat Aruchalean Taweewongsounton Yutthana Rittavee Nintita Sripaiboonkit Thokanit Montien Ngodngamthaweesuk Pitichote Hiranyatheb Thanyanan Reungwetwattana Nuttapong Ngamphaiboon Natini Jinawath |
| author_sort | Saad Ahmed |
| collection | DOAJ |
| description | Cisplatin is a widely used chemotherapeutic drug for various cancers. One of the common adverse effects of cisplatin is nephrotoxicity including acute kidney injury (AKI) and acute kidney disease (AKD). Single Nucleotide Polymorphisms (SNPs) can be used to identify cancer patients who are susceptible to developing cisplatin-induced nephrotoxicity (CIN). In this study, we validated the association between 6 SNPs in the drug metabolizing enzyme genes, SLC22A2 (rs316019) & EPHX1 (rs1051740), and the DNA repair genes, ERCC1 (rs11615 & rs3212986) & ERCC2 (rs13181 & rs1799793), and CIN in the 169 Thai patients with head and neck, lung, or esophageal cancer. Effect of these SNPs on cumulative incidence of AKD, progression-free survival (PFS), and overall survival (OS) was also assessed. EPHX1 rs1051740 TC genotype was significantly associated with AKD in co-dominant [OR 2.894, 95% CI 1.091-7.680; P = 0.033] and over-dominant [OR 2.793, 95% CI 1.333-5.851; P = 0.006] models, and with an increased cumulative incidence of AKD (P = 0.021). Additionally, ERCC2 rs13181 and rs1799793 were significantly associated with OS (P = 0.002 and 0.004). Our results reveal an association between EPHX1 rs1051740 and AKD, and confirms the previously reported associations between ERCC2 SNPs and OS. These findings may help in predicting CIN in Thai cancer patients. |
| format | Article |
| id | doaj-art-3bb8e8bb64a044c4a6a28b47093e9717 |
| institution | Kabale University |
| issn | 1932-6203 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | Public Library of Science (PLoS) |
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| series | PLoS ONE |
| spelling | doaj-art-3bb8e8bb64a044c4a6a28b47093e97172025-08-20T03:47:12ZengPublic Library of Science (PLoS)PLoS ONE1932-62032025-01-01206e032469910.1371/journal.pone.0324699EPHX1 and ERCC2 polymorphisms are associated with cisplatin-induced nephrotoxicity and prognosis in Thai cancer patients.Saad AhmedJakris Eu-AhsunthornwattanaThanaporn ThamrongjirapatAruchalean TaweewongsountonYutthana RittaveeNintita Sripaiboonkit ThokanitMontien NgodngamthaweesukPitichote HiranyathebThanyanan ReungwetwattanaNuttapong NgamphaiboonNatini JinawathCisplatin is a widely used chemotherapeutic drug for various cancers. One of the common adverse effects of cisplatin is nephrotoxicity including acute kidney injury (AKI) and acute kidney disease (AKD). Single Nucleotide Polymorphisms (SNPs) can be used to identify cancer patients who are susceptible to developing cisplatin-induced nephrotoxicity (CIN). In this study, we validated the association between 6 SNPs in the drug metabolizing enzyme genes, SLC22A2 (rs316019) & EPHX1 (rs1051740), and the DNA repair genes, ERCC1 (rs11615 & rs3212986) & ERCC2 (rs13181 & rs1799793), and CIN in the 169 Thai patients with head and neck, lung, or esophageal cancer. Effect of these SNPs on cumulative incidence of AKD, progression-free survival (PFS), and overall survival (OS) was also assessed. EPHX1 rs1051740 TC genotype was significantly associated with AKD in co-dominant [OR 2.894, 95% CI 1.091-7.680; P = 0.033] and over-dominant [OR 2.793, 95% CI 1.333-5.851; P = 0.006] models, and with an increased cumulative incidence of AKD (P = 0.021). Additionally, ERCC2 rs13181 and rs1799793 were significantly associated with OS (P = 0.002 and 0.004). Our results reveal an association between EPHX1 rs1051740 and AKD, and confirms the previously reported associations between ERCC2 SNPs and OS. These findings may help in predicting CIN in Thai cancer patients.https://doi.org/10.1371/journal.pone.0324699 |
| spellingShingle | Saad Ahmed Jakris Eu-Ahsunthornwattana Thanaporn Thamrongjirapat Aruchalean Taweewongsounton Yutthana Rittavee Nintita Sripaiboonkit Thokanit Montien Ngodngamthaweesuk Pitichote Hiranyatheb Thanyanan Reungwetwattana Nuttapong Ngamphaiboon Natini Jinawath EPHX1 and ERCC2 polymorphisms are associated with cisplatin-induced nephrotoxicity and prognosis in Thai cancer patients. PLoS ONE |
| title | EPHX1 and ERCC2 polymorphisms are associated with cisplatin-induced nephrotoxicity and prognosis in Thai cancer patients. |
| title_full | EPHX1 and ERCC2 polymorphisms are associated with cisplatin-induced nephrotoxicity and prognosis in Thai cancer patients. |
| title_fullStr | EPHX1 and ERCC2 polymorphisms are associated with cisplatin-induced nephrotoxicity and prognosis in Thai cancer patients. |
| title_full_unstemmed | EPHX1 and ERCC2 polymorphisms are associated with cisplatin-induced nephrotoxicity and prognosis in Thai cancer patients. |
| title_short | EPHX1 and ERCC2 polymorphisms are associated with cisplatin-induced nephrotoxicity and prognosis in Thai cancer patients. |
| title_sort | ephx1 and ercc2 polymorphisms are associated with cisplatin induced nephrotoxicity and prognosis in thai cancer patients |
| url | https://doi.org/10.1371/journal.pone.0324699 |
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