SNPs in genes implicated in radiation response are associated with radiotoxicity and evoke roles as predictive and prognostic biomarkers
Biomarkers are needed to individualize cancer radiation treatment. Therefore, we have investigated the association between various risk factors, including single nucleotide polymorphisms (SNPs) in candidate genes and late complications to radiotherapy in our nasopharyngeal cancer patients. A cohort...
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| Veröffentlicht in: | Radiation oncology (London, England) England), 2013-05, Vol.8 (1), p.125-125 |
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| creator | Alsbeih, Ghazi El-Sebaie, Medhat Al-Harbi, Najla Al-Hadyan, Khaled Shoukri, Mohamed Al-Rajhi, Nasser |
| description | Biomarkers are needed to individualize cancer radiation treatment. Therefore, we have investigated the association between various risk factors, including single nucleotide polymorphisms (SNPs) in candidate genes and late complications to radiotherapy in our nasopharyngeal cancer patients.
A cohort of 155 patients was included. Normal tissue fibrosis was scored using RTOG/EORTC grading system. A total of 45 SNPs in 11 candidate genes (ATM, XRCC1, XRCC3, XRCC4, XRCC5, PRKDC, LIG4, TP53, HDM2, CDKN1A, TGFB1) were genotyped by direct genomic DNA sequencing. Patients with severe fibrosis (cases, G3-4, n = 48) were compared to controls (G0-2, n = 107).
Univariate analysis showed significant association (P < 0.05) with radiation complications for 6 SNPs (ATM G/A rs1801516, HDM2 promoter T/G rs2279744 and T/A rs1196333, XRCC1 G/A rs25487, XRCC5 T/C rs1051677 and TGFB1 C/T rs1800469). In addition, Kaplan-Meier analyses have also highlighted significant association between genotypes and length of patients' follow-up after radiotherapy. Multivariate logistic regression has further sustained these results suggesting predictive and prognostic roles of SNPs.
Univariate and multivariate analysis suggest that radiation toxicity in radiotherapy patients are associated with certain SNPs, in genes including HDM2 promoter studied for the 1st time. These results support the use of SNPs as genetic predictive markers for clinical radiosensitivity and evoke a prognostic role for length of patients' follow-up after radiotherapy. |
| doi_str_mv | 10.1186/1748-717X-8-125 |
| format | Article |
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A cohort of 155 patients was included. Normal tissue fibrosis was scored using RTOG/EORTC grading system. A total of 45 SNPs in 11 candidate genes (ATM, XRCC1, XRCC3, XRCC4, XRCC5, PRKDC, LIG4, TP53, HDM2, CDKN1A, TGFB1) were genotyped by direct genomic DNA sequencing. Patients with severe fibrosis (cases, G3-4, n = 48) were compared to controls (G0-2, n = 107).
Univariate analysis showed significant association (P < 0.05) with radiation complications for 6 SNPs (ATM G/A rs1801516, HDM2 promoter T/G rs2279744 and T/A rs1196333, XRCC1 G/A rs25487, XRCC5 T/C rs1051677 and TGFB1 C/T rs1800469). In addition, Kaplan-Meier analyses have also highlighted significant association between genotypes and length of patients' follow-up after radiotherapy. Multivariate logistic regression has further sustained these results suggesting predictive and prognostic roles of SNPs.
Univariate and multivariate analysis suggest that radiation toxicity in radiotherapy patients are associated with certain SNPs, in genes including HDM2 promoter studied for the 1st time. These results support the use of SNPs as genetic predictive markers for clinical radiosensitivity and evoke a prognostic role for length of patients' follow-up after radiotherapy.</description><identifier>ISSN: 1748-717X</identifier><identifier>EISSN: 1748-717X</identifier><identifier>DOI: 10.1186/1748-717X-8-125</identifier><identifier>PMID: 23697595</identifier><language>eng</language><publisher>England: BioMed Central Ltd</publisher><subject>Adolescent ; Adult ; Aged ; Analysis ; Biological markers ; Biomarkers ; Biomarkers, Tumor - genetics ; Cancer ; Cancer therapies ; Carcinoma ; Cell cycle ; Chemotherapy ; Confidence intervals ; DNA repair ; Female ; Fibrosis - etiology ; Fibrosis - genetics ; Genealogy ; Genes ; Genomes ; Genotype ; Head & neck cancer ; Humans ; Male ; Medical research ; Medicine, Experimental ; Middle Aged ; Nasopharyngeal cancer ; Nasopharyngeal Carcinoma ; Nasopharyngeal Neoplasms - diagnosis ; Nasopharyngeal Neoplasms - genetics ; Nasopharyngeal Neoplasms - radiotherapy ; Polymorphism, Single Nucleotide ; Prognosis ; Radiation ; Radiation Injuries - genetics ; Radiation therapy ; Radiation Tolerance - genetics ; Radiotherapy - adverse effects ; Reverse Transcriptase Polymerase Chain Reaction ; Single nucleotide polymorphisms ; Statistical analysis ; Studies ; Thermal cycling ; Young Adult</subject><ispartof>Radiation oncology (London, England), 2013-05, Vol.8 (1), p.125-125</ispartof><rights>COPYRIGHT 2013 BioMed Central Ltd.</rights><rights>2013 Alsbeih et al.; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.</rights><rights>Copyright © 2013 Alsbeih et al.; licensee BioMed Central Ltd. 2013 Alsbeih et al.; licensee BioMed Central Ltd.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC3679989/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC3679989/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,315,728,781,785,865,886,27929,27930,53796,53798</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/23697595$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Alsbeih, Ghazi</creatorcontrib><creatorcontrib>El-Sebaie, Medhat</creatorcontrib><creatorcontrib>Al-Harbi, Najla</creatorcontrib><creatorcontrib>Al-Hadyan, Khaled</creatorcontrib><creatorcontrib>Shoukri, Mohamed</creatorcontrib><creatorcontrib>Al-Rajhi, Nasser</creatorcontrib><title>SNPs in genes implicated in radiation response are associated with radiotoxicity and evoke roles as predictive and prognostic biomarkers</title><title>Radiation oncology (London, England)</title><addtitle>Radiat Oncol</addtitle><description>Biomarkers are needed to individualize cancer radiation treatment. Therefore, we have investigated the association between various risk factors, including single nucleotide polymorphisms (SNPs) in candidate genes and late complications to radiotherapy in our nasopharyngeal cancer patients.
A cohort of 155 patients was included. Normal tissue fibrosis was scored using RTOG/EORTC grading system. A total of 45 SNPs in 11 candidate genes (ATM, XRCC1, XRCC3, XRCC4, XRCC5, PRKDC, LIG4, TP53, HDM2, CDKN1A, TGFB1) were genotyped by direct genomic DNA sequencing. Patients with severe fibrosis (cases, G3-4, n = 48) were compared to controls (G0-2, n = 107).
Univariate analysis showed significant association (P < 0.05) with radiation complications for 6 SNPs (ATM G/A rs1801516, HDM2 promoter T/G rs2279744 and T/A rs1196333, XRCC1 G/A rs25487, XRCC5 T/C rs1051677 and TGFB1 C/T rs1800469). In addition, Kaplan-Meier analyses have also highlighted significant association between genotypes and length of patients' follow-up after radiotherapy. Multivariate logistic regression has further sustained these results suggesting predictive and prognostic roles of SNPs.
Univariate and multivariate analysis suggest that radiation toxicity in radiotherapy patients are associated with certain SNPs, in genes including HDM2 promoter studied for the 1st time. These results support the use of SNPs as genetic predictive markers for clinical radiosensitivity and evoke a prognostic role for length of patients' follow-up after radiotherapy.</description><subject>Adolescent</subject><subject>Adult</subject><subject>Aged</subject><subject>Analysis</subject><subject>Biological markers</subject><subject>Biomarkers</subject><subject>Biomarkers, Tumor - genetics</subject><subject>Cancer</subject><subject>Cancer therapies</subject><subject>Carcinoma</subject><subject>Cell cycle</subject><subject>Chemotherapy</subject><subject>Confidence intervals</subject><subject>DNA repair</subject><subject>Female</subject><subject>Fibrosis - etiology</subject><subject>Fibrosis - genetics</subject><subject>Genealogy</subject><subject>Genes</subject><subject>Genomes</subject><subject>Genotype</subject><subject>Head & neck cancer</subject><subject>Humans</subject><subject>Male</subject><subject>Medical research</subject><subject>Medicine, Experimental</subject><subject>Middle Aged</subject><subject>Nasopharyngeal cancer</subject><subject>Nasopharyngeal Carcinoma</subject><subject>Nasopharyngeal Neoplasms - diagnosis</subject><subject>Nasopharyngeal Neoplasms - genetics</subject><subject>Nasopharyngeal Neoplasms - radiotherapy</subject><subject>Polymorphism, Single Nucleotide</subject><subject>Prognosis</subject><subject>Radiation</subject><subject>Radiation Injuries - genetics</subject><subject>Radiation therapy</subject><subject>Radiation Tolerance - genetics</subject><subject>Radiotherapy - adverse effects</subject><subject>Reverse Transcriptase Polymerase Chain Reaction</subject><subject>Single nucleotide polymorphisms</subject><subject>Statistical analysis</subject><subject>Studies</subject><subject>Thermal cycling</subject><subject>Young Adult</subject><issn>1748-717X</issn><issn>1748-717X</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2013</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>ABUWG</sourceid><sourceid>AFKRA</sourceid><sourceid>AZQEC</sourceid><sourceid>BENPR</sourceid><sourceid>CCPQU</sourceid><sourceid>DWQXO</sourceid><recordid>eNptkl1vFSEQhjdGYz_02juziTfebIVl-boxqY1Vk0ZN1MQ7wsLsKe0urMA52n_gz5Y9rbXHNIQwzDy8zDBU1TOMjjAW7BXmnWg45t8b0eCWPqj2bz0P79h71UFKFwh1lCD5uNprCZOcSrpf_f7y8XOqna9X4KEY0zw6ozPYxRe1dTq7UCxIc_AJah3LTCkYt4V-uny-xUIOv5xx-arW3tawCZdQxzAWSZ3qOYJ1JrsNbKNzDCsfUnam7l2YdLyEmJ5UjwY9Jnh6sx5W307ffj1535x9evfh5Pis6UvyuQGNGGNUIyugFVxrKVoiB2Ms6QfB-5bowZoO6Y7Z1rQtpYT2kvSCDW237A6r19e687qfwBrwOepRzdGVRK5U0E7tRrw7V6uwUYRxKYUsAm-uBZbc7xfYjZgwqaUTaumEEqr0qYi8vMkihh9rSFlNLhkYR-0hrJPCREqJJJakoC_-Qy_COvryRoVijGOJEP1HrfQIyvkhlLvNIqqOKek4LqXjQh3dQ5VhYXImeBhc8e8ceH73tW6r_PuByB9rFMq8</recordid><startdate>20130522</startdate><enddate>20130522</enddate><creator>Alsbeih, Ghazi</creator><creator>El-Sebaie, Medhat</creator><creator>Al-Harbi, Najla</creator><creator>Al-Hadyan, Khaled</creator><creator>Shoukri, Mohamed</creator><creator>Al-Rajhi, Nasser</creator><general>BioMed Central Ltd</general><general>BioMed Central</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>3V.</scope><scope>7QO</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>8FD</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>AZQEC</scope><scope>BENPR</scope><scope>CCPQU</scope><scope>DWQXO</scope><scope>FR3</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>K9.</scope><scope>M0S</scope><scope>M1P</scope><scope>P64</scope><scope>PIMPY</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>7U7</scope><scope>C1K</scope><scope>RC3</scope><scope>5PM</scope></search><sort><creationdate>20130522</creationdate><title>SNPs in genes implicated in radiation response are associated with radiotoxicity and evoke roles as predictive and prognostic biomarkers</title><author>Alsbeih, Ghazi ; El-Sebaie, Medhat ; Al-Harbi, Najla ; Al-Hadyan, Khaled ; Shoukri, Mohamed ; Al-Rajhi, Nasser</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-b453t-ea06665a0d8e287aa98239fccd3bf87b23afdc40a46d2c225535b93b86f242553</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2013</creationdate><topic>Adolescent</topic><topic>Adult</topic><topic>Aged</topic><topic>Analysis</topic><topic>Biological markers</topic><topic>Biomarkers</topic><topic>Biomarkers, Tumor - genetics</topic><topic>Cancer</topic><topic>Cancer therapies</topic><topic>Carcinoma</topic><topic>Cell cycle</topic><topic>Chemotherapy</topic><topic>Confidence intervals</topic><topic>DNA repair</topic><topic>Female</topic><topic>Fibrosis - etiology</topic><topic>Fibrosis - genetics</topic><topic>Genealogy</topic><topic>Genes</topic><topic>Genomes</topic><topic>Genotype</topic><topic>Head & neck cancer</topic><topic>Humans</topic><topic>Male</topic><topic>Medical research</topic><topic>Medicine, Experimental</topic><topic>Middle Aged</topic><topic>Nasopharyngeal cancer</topic><topic>Nasopharyngeal Carcinoma</topic><topic>Nasopharyngeal Neoplasms - diagnosis</topic><topic>Nasopharyngeal Neoplasms - genetics</topic><topic>Nasopharyngeal Neoplasms - radiotherapy</topic><topic>Polymorphism, Single Nucleotide</topic><topic>Prognosis</topic><topic>Radiation</topic><topic>Radiation Injuries - genetics</topic><topic>Radiation therapy</topic><topic>Radiation Tolerance - genetics</topic><topic>Radiotherapy - adverse effects</topic><topic>Reverse Transcriptase Polymerase Chain Reaction</topic><topic>Single nucleotide polymorphisms</topic><topic>Statistical analysis</topic><topic>Studies</topic><topic>Thermal cycling</topic><topic>Young Adult</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Alsbeih, Ghazi</creatorcontrib><creatorcontrib>El-Sebaie, Medhat</creatorcontrib><creatorcontrib>Al-Harbi, Najla</creatorcontrib><creatorcontrib>Al-Hadyan, Khaled</creatorcontrib><creatorcontrib>Shoukri, Mohamed</creatorcontrib><creatorcontrib>Al-Rajhi, Nasser</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>ProQuest Central (Corporate)</collection><collection>Biotechnology Research Abstracts</collection><collection>Health & Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Medical Database (Alumni Edition)</collection><collection>Technology Research Database</collection><collection>Hospital Premium Collection</collection><collection>Hospital Premium Collection (Alumni Edition)</collection><collection>ProQuest Central (Alumni) (purchase pre-March 2016)</collection><collection>ProQuest Central (Alumni Edition)</collection><collection>ProQuest Central UK/Ireland</collection><collection>ProQuest Central Essentials</collection><collection>ProQuest Central</collection><collection>ProQuest One Community College</collection><collection>ProQuest Central Korea</collection><collection>Engineering Research Database</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>Medical Database</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>Publicly Available Content Database</collection><collection>ProQuest One Academic Eastern Edition (DO NOT USE)</collection><collection>ProQuest One Academic</collection><collection>ProQuest One Academic UKI Edition</collection><collection>ProQuest Central China</collection><collection>Toxicology Abstracts</collection><collection>Environmental Sciences and Pollution Management</collection><collection>Genetics Abstracts</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Radiation oncology (London, England)</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Alsbeih, Ghazi</au><au>El-Sebaie, Medhat</au><au>Al-Harbi, Najla</au><au>Al-Hadyan, Khaled</au><au>Shoukri, Mohamed</au><au>Al-Rajhi, Nasser</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>SNPs in genes implicated in radiation response are associated with radiotoxicity and evoke roles as predictive and prognostic biomarkers</atitle><jtitle>Radiation oncology (London, England)</jtitle><addtitle>Radiat Oncol</addtitle><date>2013-05-22</date><risdate>2013</risdate><volume>8</volume><issue>1</issue><spage>125</spage><epage>125</epage><pages>125-125</pages><issn>1748-717X</issn><eissn>1748-717X</eissn><abstract>Biomarkers are needed to individualize cancer radiation treatment. Therefore, we have investigated the association between various risk factors, including single nucleotide polymorphisms (SNPs) in candidate genes and late complications to radiotherapy in our nasopharyngeal cancer patients.
A cohort of 155 patients was included. Normal tissue fibrosis was scored using RTOG/EORTC grading system. A total of 45 SNPs in 11 candidate genes (ATM, XRCC1, XRCC3, XRCC4, XRCC5, PRKDC, LIG4, TP53, HDM2, CDKN1A, TGFB1) were genotyped by direct genomic DNA sequencing. Patients with severe fibrosis (cases, G3-4, n = 48) were compared to controls (G0-2, n = 107).
Univariate analysis showed significant association (P < 0.05) with radiation complications for 6 SNPs (ATM G/A rs1801516, HDM2 promoter T/G rs2279744 and T/A rs1196333, XRCC1 G/A rs25487, XRCC5 T/C rs1051677 and TGFB1 C/T rs1800469). In addition, Kaplan-Meier analyses have also highlighted significant association between genotypes and length of patients' follow-up after radiotherapy. Multivariate logistic regression has further sustained these results suggesting predictive and prognostic roles of SNPs.
Univariate and multivariate analysis suggest that radiation toxicity in radiotherapy patients are associated with certain SNPs, in genes including HDM2 promoter studied for the 1st time. These results support the use of SNPs as genetic predictive markers for clinical radiosensitivity and evoke a prognostic role for length of patients' follow-up after radiotherapy.</abstract><cop>England</cop><pub>BioMed Central Ltd</pub><pmid>23697595</pmid><doi>10.1186/1748-717X-8-125</doi><tpages>1</tpages><oa>free_for_read</oa></addata></record> |
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| subjects | Adolescent Adult Aged Analysis Biological markers Biomarkers Biomarkers, Tumor - genetics Cancer Cancer therapies Carcinoma Cell cycle Chemotherapy Confidence intervals DNA repair Female Fibrosis - etiology Fibrosis - genetics Genealogy Genes Genomes Genotype Head & neck cancer Humans Male Medical research Medicine, Experimental Middle Aged Nasopharyngeal cancer Nasopharyngeal Carcinoma Nasopharyngeal Neoplasms - diagnosis Nasopharyngeal Neoplasms - genetics Nasopharyngeal Neoplasms - radiotherapy Polymorphism, Single Nucleotide Prognosis Radiation Radiation Injuries - genetics Radiation therapy Radiation Tolerance - genetics Radiotherapy - adverse effects Reverse Transcriptase Polymerase Chain Reaction Single nucleotide polymorphisms Statistical analysis Studies Thermal cycling Young Adult |
| title | SNPs in genes implicated in radiation response are associated with radiotoxicity and evoke roles as predictive and prognostic biomarkers |
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