<i>KRAS</i>, <i>NRAS</i>, and <i>BRAF</i> Hot-Spot Mutations in Relation to Sidedness of Primary Colorectal Cancer: A Retrospective Cohort Study
<b>Background/Objective:</b> Studies have shown an association between colorectal cancer (CRC) sidedness and gene mutations that may affect CRC clinical behavior. This study examined the association between specific <i>KRAS</i>, <i>NRAS</i>, and <i>BRAF</...
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2025-01-01
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| author | Omer Abdelgadir Yong-Fang Kuo Anthony O. Okorodudu M. Firoze Khan Yu-Wei Cheng Jianli Dong |
| author_facet | Omer Abdelgadir Yong-Fang Kuo Anthony O. Okorodudu M. Firoze Khan Yu-Wei Cheng Jianli Dong |
| author_sort | Omer Abdelgadir |
| collection | DOAJ |
| description | <b>Background/Objective:</b> Studies have shown an association between colorectal cancer (CRC) sidedness and gene mutations that may affect CRC clinical behavior. This study examined the association between specific <i>KRAS</i>, <i>NRAS</i>, and <i>BRAF</i> hot-spot mutations and primary CRC sidedness. <b>Methods:</b> We performed a retrospective cohort analysis of 722 patients diagnosed with primary CRC and tested for <i>KRAS</i>, <i>NRAS</i>, and <i>BRAF</i> hot-spot mutations at the University of Texas Medical Branch (UTMB) from January 2016 through July 2023. Multivariable logistic regressions analyses were conducted. <b>Results:</b><i>KRAS</i>, <i>NRAS</i>, and <i>BRAF</i> hot-spot mutations rates were 37.8%, 4.6%, and 6.1%, respectively. Right-sided primary CRC had the highest prevalence of mutated tumors (64%). <i>KRAS</i> and <i>BRAF</i> hot-spot mutations were significantly different according to tumor sidedness. <i>KRAS</i> p.Gly12Asp, p.Gly12Val, and p.Gly13Asp showed a significantly increased likelihood of right-sided primary CRC compared to <i>KRAS</i> wildtype, 128%, 134%, and 221% higher, respectively. Conversely, <i>KRAS</i> p.Gly12Val and p.Gly13Asp mutations were associated with decreased likelihood of rectal cancer (53% lower) and left-sided tumors (56% lower), respectively. <i>BRAF</i> p.Val600Glu mutation, as opposed to <i>BRAF</i> wildtype, was associated with a 278% higher likelihood of right-sided CRC. No significant associations were observed between <i>NRAS</i> mutations and primary CRC sidedness. <b>Conclusions:</b> In primary CRC, specific mutations in <i>KRAS</i> (p.Gly12Asp, p.Gly12Val, and p.Gly13Asp) and <i>BRAF</i> p.Val600Glu were associated with increased likelihood of right-sided tumors. <i>KRAS</i> p.Gly12Val and p.Gly13Asp mutations were associated with decreased likelihood of rectal cancer and left-sided tumors, respectively. These findings suggest that tumorigenesis and mutational processes differ based on tumor sidedness. Further studies are needed to substantiate these findings. |
| format | Article |
| id | doaj-art-c88dc9ef572342bc9c4a095a404db3cc |
| institution | Kabale University |
| issn | 2075-4418 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | MDPI AG |
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| spelling | doaj-art-c88dc9ef572342bc9c4a095a404db3cc2025-01-24T13:28:52ZengMDPI AGDiagnostics2075-44182025-01-0115214210.3390/diagnostics15020142<i>KRAS</i>, <i>NRAS</i>, and <i>BRAF</i> Hot-Spot Mutations in Relation to Sidedness of Primary Colorectal Cancer: A Retrospective Cohort StudyOmer Abdelgadir0Yong-Fang Kuo1Anthony O. Okorodudu2M. Firoze Khan3Yu-Wei Cheng4Jianli Dong5Graduate School of Biomedical Science, University of Texas Medical Branch, Galveston, TX 77555, USASchool of Public and Population Health, University of Texas Medical Branch, Galveston, TX 77555, USADepartment of Pathology, University of Texas Medical Branch, Galveston, TX 77555, USADepartment of Pathology, University of Texas Medical Branch, Galveston, TX 77555, USADepartment of Laboratory Medicine, Cleveland Clinic, Cleveland, OH 44195, USADepartment of Pathology, University of Texas Medical Branch, Galveston, TX 77555, USA<b>Background/Objective:</b> Studies have shown an association between colorectal cancer (CRC) sidedness and gene mutations that may affect CRC clinical behavior. This study examined the association between specific <i>KRAS</i>, <i>NRAS</i>, and <i>BRAF</i> hot-spot mutations and primary CRC sidedness. <b>Methods:</b> We performed a retrospective cohort analysis of 722 patients diagnosed with primary CRC and tested for <i>KRAS</i>, <i>NRAS</i>, and <i>BRAF</i> hot-spot mutations at the University of Texas Medical Branch (UTMB) from January 2016 through July 2023. Multivariable logistic regressions analyses were conducted. <b>Results:</b><i>KRAS</i>, <i>NRAS</i>, and <i>BRAF</i> hot-spot mutations rates were 37.8%, 4.6%, and 6.1%, respectively. Right-sided primary CRC had the highest prevalence of mutated tumors (64%). <i>KRAS</i> and <i>BRAF</i> hot-spot mutations were significantly different according to tumor sidedness. <i>KRAS</i> p.Gly12Asp, p.Gly12Val, and p.Gly13Asp showed a significantly increased likelihood of right-sided primary CRC compared to <i>KRAS</i> wildtype, 128%, 134%, and 221% higher, respectively. Conversely, <i>KRAS</i> p.Gly12Val and p.Gly13Asp mutations were associated with decreased likelihood of rectal cancer (53% lower) and left-sided tumors (56% lower), respectively. <i>BRAF</i> p.Val600Glu mutation, as opposed to <i>BRAF</i> wildtype, was associated with a 278% higher likelihood of right-sided CRC. No significant associations were observed between <i>NRAS</i> mutations and primary CRC sidedness. <b>Conclusions:</b> In primary CRC, specific mutations in <i>KRAS</i> (p.Gly12Asp, p.Gly12Val, and p.Gly13Asp) and <i>BRAF</i> p.Val600Glu were associated with increased likelihood of right-sided tumors. <i>KRAS</i> p.Gly12Val and p.Gly13Asp mutations were associated with decreased likelihood of rectal cancer and left-sided tumors, respectively. These findings suggest that tumorigenesis and mutational processes differ based on tumor sidedness. Further studies are needed to substantiate these findings.https://www.mdpi.com/2075-4418/15/2/142<i>KRAS</i><i>NRAS</i><i>BRAF</i>hot-spot mutationcolorectal cancertumor sidedness |
| spellingShingle | Omer Abdelgadir Yong-Fang Kuo Anthony O. Okorodudu M. Firoze Khan Yu-Wei Cheng Jianli Dong <i>KRAS</i>, <i>NRAS</i>, and <i>BRAF</i> Hot-Spot Mutations in Relation to Sidedness of Primary Colorectal Cancer: A Retrospective Cohort Study Diagnostics <i>KRAS</i> <i>NRAS</i> <i>BRAF</i> hot-spot mutation colorectal cancer tumor sidedness |
| title | <i>KRAS</i>, <i>NRAS</i>, and <i>BRAF</i> Hot-Spot Mutations in Relation to Sidedness of Primary Colorectal Cancer: A Retrospective Cohort Study |
| title_full | <i>KRAS</i>, <i>NRAS</i>, and <i>BRAF</i> Hot-Spot Mutations in Relation to Sidedness of Primary Colorectal Cancer: A Retrospective Cohort Study |
| title_fullStr | <i>KRAS</i>, <i>NRAS</i>, and <i>BRAF</i> Hot-Spot Mutations in Relation to Sidedness of Primary Colorectal Cancer: A Retrospective Cohort Study |
| title_full_unstemmed | <i>KRAS</i>, <i>NRAS</i>, and <i>BRAF</i> Hot-Spot Mutations in Relation to Sidedness of Primary Colorectal Cancer: A Retrospective Cohort Study |
| title_short | <i>KRAS</i>, <i>NRAS</i>, and <i>BRAF</i> Hot-Spot Mutations in Relation to Sidedness of Primary Colorectal Cancer: A Retrospective Cohort Study |
| title_sort | i kras i i nras i and i braf i hot spot mutations in relation to sidedness of primary colorectal cancer a retrospective cohort study |
| topic | <i>KRAS</i> <i>NRAS</i> <i>BRAF</i> hot-spot mutation colorectal cancer tumor sidedness |
| url | https://www.mdpi.com/2075-4418/15/2/142 |
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