A Polymorphism Within the Promoter of the TGFβ1 Gene Is Associated With Radiation Sensitivity Using an Objective Radiologic Endpoint
Purpose To evaluate whether single nucleotide polymorphisms (SNPs) in the transforming growth factor-β1 ( TGFβ1 ) gene are associated with radiation sensitivity using an objective radiologic endpoint. Methods and Materials Preradiation therapy and serial postradiation therapy single photon emission...
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| Veröffentlicht in: | International journal of radiation oncology, biology, physics biology, physics, 2012-02, Vol.82 (2), p.e247-e255 |
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| creator | Kelsey, Chris R., M.D Jackson, Lauren, B.S Langdon, Scott, Ph.D Owzar, Kouros, Ph.D Hubbs, Jessica, M.S Vujaskovic, Zeljko, M.D., Ph.D Das, Shiva, Ph.D Marks, Lawrence B., M.D |
| description | Purpose To evaluate whether single nucleotide polymorphisms (SNPs) in the transforming growth factor-β1 ( TGFβ1 ) gene are associated with radiation sensitivity using an objective radiologic endpoint. Methods and Materials Preradiation therapy and serial postradiation therapy single photon emission computed tomography (SPECT) lung perfusion scans were obtained in patients undergoing treatment for lung cancer. Serial blood samples were obtained to measure circulating levels of TGFβ1. Changes in regional perfusion were related to regional radiation dose yielding a patient-specific dose–response curve, reflecting the patient’s inherent sensitivity to radiation therapy. Six TGFβ1 SNPs (-988, -800, -509, 869, 941, and 1655) were assessed using high-resolution melting assays and DNA sequencing. The association between genotype and slope of the dose–response curve, and genotype and TGFβ1 ratio (4-week/preradiation therapy), was analyzed using the Kruskal-Wallis test. Results 39 white patients with preradiation therapy and ≥6-month postradiation therapy SPECT scans and blood samples were identified. Increasing slope of the dose–response curve was associated with the C(-509)T SNP ( p = 0.035), but not the other analyzed SNPs. This SNP was also associated with higher TGFβ1 ratios. Conclusions This study suggests that a polymorphism within the promoter of the TGFβ1 gene is associated with increased radiation sensitivity (defined objectively by dose-dependent changes in SPECT lung perfusion). |
| doi_str_mv | 10.1016/j.ijrobp.2011.02.064 |
| format | Article |
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Methods and Materials Preradiation therapy and serial postradiation therapy single photon emission computed tomography (SPECT) lung perfusion scans were obtained in patients undergoing treatment for lung cancer. Serial blood samples were obtained to measure circulating levels of TGFβ1. Changes in regional perfusion were related to regional radiation dose yielding a patient-specific dose–response curve, reflecting the patient’s inherent sensitivity to radiation therapy. Six TGFβ1 SNPs (-988, -800, -509, 869, 941, and 1655) were assessed using high-resolution melting assays and DNA sequencing. The association between genotype and slope of the dose–response curve, and genotype and TGFβ1 ratio (4-week/preradiation therapy), was analyzed using the Kruskal-Wallis test. Results 39 white patients with preradiation therapy and ≥6-month postradiation therapy SPECT scans and blood samples were identified. Increasing slope of the dose–response curve was associated with the C(-509)T SNP ( p = 0.035), but not the other analyzed SNPs. This SNP was also associated with higher TGFβ1 ratios. Conclusions This study suggests that a polymorphism within the promoter of the TGFβ1 gene is associated with increased radiation sensitivity (defined objectively by dose-dependent changes in SPECT lung perfusion).</description><identifier>ISSN: 0360-3016</identifier><identifier>EISSN: 1879-355X</identifier><identifier>DOI: 10.1016/j.ijrobp.2011.02.064</identifier><identifier>PMID: 21605940</identifier><language>eng</language><publisher>United States: Elsevier Inc</publisher><subject>Aged ; Aged, 80 and over ; Dose-Response Relationship, Radiation ; Female ; Genotype ; Hematology, Oncology and Palliative Medicine ; Humans ; Lung - blood supply ; Lung - diagnostic imaging ; Lung - radiation effects ; Lung Neoplasms - blood ; Lung Neoplasms - blood supply ; Lung Neoplasms - diagnostic imaging ; Lung Neoplasms - genetics ; Lung Neoplasms - radiotherapy ; Male ; Middle Aged ; Neoplasm Proteins - blood ; Neoplasm Proteins - genetics ; Polymorphism, Single Nucleotide ; Promoter Regions, Genetic - genetics ; Radiation Injuries - blood ; Radiation Injuries - genetics ; Radiation Injuries - physiopathology ; Radiation sensitivity ; Radiation Tolerance - genetics ; Radiology ; Radiotherapy Dosage ; Sequence Analysis, DNA - methods ; Single nucleotide polymorphism ; Single photon emission computed tomography ; Statistics, Nonparametric ; Tomography, Emission-Computed, Single-Photon ; Transforming Growth Factor beta1 - blood ; Transforming Growth Factor beta1 - genetics ; Transforming growth factor β1</subject><ispartof>International journal of radiation oncology, biology, physics, 2012-02, Vol.82 (2), p.e247-e255</ispartof><rights>Elsevier Inc.</rights><rights>2012 Elsevier Inc.</rights><rights>Copyright © 2012 Elsevier Inc. All rights reserved.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c331t-b470c8364f1e724c9014858cc5b9b592b02db892af8f5fea91b81988c62578bc3</citedby><cites>FETCH-LOGICAL-c331t-b470c8364f1e724c9014858cc5b9b592b02db892af8f5fea91b81988c62578bc3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://dx.doi.org/10.1016/j.ijrobp.2011.02.064$$EHTML$$P50$$Gelsevier$$H</linktohtml><link.rule.ids>314,780,784,3548,27923,27924,45994</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/21605940$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Kelsey, Chris R., M.D</creatorcontrib><creatorcontrib>Jackson, Lauren, B.S</creatorcontrib><creatorcontrib>Langdon, Scott, Ph.D</creatorcontrib><creatorcontrib>Owzar, Kouros, Ph.D</creatorcontrib><creatorcontrib>Hubbs, Jessica, M.S</creatorcontrib><creatorcontrib>Vujaskovic, Zeljko, M.D., Ph.D</creatorcontrib><creatorcontrib>Das, Shiva, Ph.D</creatorcontrib><creatorcontrib>Marks, Lawrence B., M.D</creatorcontrib><title>A Polymorphism Within the Promoter of the TGFβ1 Gene Is Associated With Radiation Sensitivity Using an Objective Radiologic Endpoint</title><title>International journal of radiation oncology, biology, physics</title><addtitle>Int J Radiat Oncol Biol Phys</addtitle><description>Purpose To evaluate whether single nucleotide polymorphisms (SNPs) in the transforming growth factor-β1 ( TGFβ1 ) gene are associated with radiation sensitivity using an objective radiologic endpoint. Methods and Materials Preradiation therapy and serial postradiation therapy single photon emission computed tomography (SPECT) lung perfusion scans were obtained in patients undergoing treatment for lung cancer. Serial blood samples were obtained to measure circulating levels of TGFβ1. Changes in regional perfusion were related to regional radiation dose yielding a patient-specific dose–response curve, reflecting the patient’s inherent sensitivity to radiation therapy. Six TGFβ1 SNPs (-988, -800, -509, 869, 941, and 1655) were assessed using high-resolution melting assays and DNA sequencing. The association between genotype and slope of the dose–response curve, and genotype and TGFβ1 ratio (4-week/preradiation therapy), was analyzed using the Kruskal-Wallis test. Results 39 white patients with preradiation therapy and ≥6-month postradiation therapy SPECT scans and blood samples were identified. Increasing slope of the dose–response curve was associated with the C(-509)T SNP ( p = 0.035), but not the other analyzed SNPs. This SNP was also associated with higher TGFβ1 ratios. Conclusions This study suggests that a polymorphism within the promoter of the TGFβ1 gene is associated with increased radiation sensitivity (defined objectively by dose-dependent changes in SPECT lung perfusion).</description><subject>Aged</subject><subject>Aged, 80 and over</subject><subject>Dose-Response Relationship, Radiation</subject><subject>Female</subject><subject>Genotype</subject><subject>Hematology, Oncology and Palliative Medicine</subject><subject>Humans</subject><subject>Lung - blood supply</subject><subject>Lung - diagnostic imaging</subject><subject>Lung - radiation effects</subject><subject>Lung Neoplasms - blood</subject><subject>Lung Neoplasms - blood supply</subject><subject>Lung Neoplasms - diagnostic imaging</subject><subject>Lung Neoplasms - genetics</subject><subject>Lung Neoplasms - radiotherapy</subject><subject>Male</subject><subject>Middle Aged</subject><subject>Neoplasm Proteins - blood</subject><subject>Neoplasm Proteins - genetics</subject><subject>Polymorphism, Single Nucleotide</subject><subject>Promoter Regions, Genetic - genetics</subject><subject>Radiation Injuries - blood</subject><subject>Radiation Injuries - genetics</subject><subject>Radiation Injuries - physiopathology</subject><subject>Radiation sensitivity</subject><subject>Radiation Tolerance - genetics</subject><subject>Radiology</subject><subject>Radiotherapy Dosage</subject><subject>Sequence Analysis, DNA - methods</subject><subject>Single nucleotide polymorphism</subject><subject>Single photon emission computed tomography</subject><subject>Statistics, Nonparametric</subject><subject>Tomography, Emission-Computed, Single-Photon</subject><subject>Transforming Growth Factor beta1 - blood</subject><subject>Transforming Growth Factor beta1 - genetics</subject><subject>Transforming growth factor β1</subject><issn>0360-3016</issn><issn>1879-355X</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2012</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFks9u1DAQhy0EokvhDRDyjVOCJ3-dC9KqapdKlVrRVnCzYmfSnZDYi52ttA_AC_EgPBPe3cKBCydrrO83o_k0jL0FkYKA6sOQ0uCd3qSZAEhFloqqeMYWIOsmycvy63O2EHklkjzCJ-xVCIMQkayLl-wkg0qUTSEW7MeS37hxNzm_WVOY-Bea12T5vEZ-493kZvTc9Yf6bnXx6yfwFVrkl4EvQ3CG2hm7Q4h_brtYkbP8Fm2gmR5p3vH7QPaBt5Zf6wFN_MQD6Eb3QIaf227jyM6v2Yu-HQO-eXpP2f3F-d3Zp-TqenV5trxKTJ7DnOiiFkbmVdED1llhGgGFLKUxpW502WRaZJ2WTdb2si97bBvQEhopTZWVtdQmP2Xvj3033n3fYpjVRMHgOLYW3TaoBqoyg1xCJIsjabwLwWOvNp6m1u8UCLX3rwZ19K_2_pXIVPQfY--eBmz1hN3f0B_hEfh4BDCu-UjoVTCE1mBHPvpRnaP_Tfi3gRnJkmnHb7jDMLitt1GhAhViQN3ub2B_AgBCFFVs8BuBda62</recordid><startdate>20120201</startdate><enddate>20120201</enddate><creator>Kelsey, Chris R., M.D</creator><creator>Jackson, Lauren, B.S</creator><creator>Langdon, Scott, Ph.D</creator><creator>Owzar, Kouros, Ph.D</creator><creator>Hubbs, Jessica, M.S</creator><creator>Vujaskovic, Zeljko, M.D., Ph.D</creator><creator>Das, Shiva, Ph.D</creator><creator>Marks, Lawrence B., M.D</creator><general>Elsevier Inc</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7X8</scope></search><sort><creationdate>20120201</creationdate><title>A Polymorphism Within the Promoter of the TGFβ1 Gene Is Associated With Radiation Sensitivity Using an Objective Radiologic Endpoint</title><author>Kelsey, Chris R., M.D ; Jackson, Lauren, B.S ; Langdon, Scott, Ph.D ; Owzar, Kouros, Ph.D ; Hubbs, Jessica, M.S ; Vujaskovic, Zeljko, M.D., Ph.D ; Das, Shiva, Ph.D ; Marks, Lawrence B., M.D</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c331t-b470c8364f1e724c9014858cc5b9b592b02db892af8f5fea91b81988c62578bc3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2012</creationdate><topic>Aged</topic><topic>Aged, 80 and over</topic><topic>Dose-Response Relationship, Radiation</topic><topic>Female</topic><topic>Genotype</topic><topic>Hematology, Oncology and Palliative Medicine</topic><topic>Humans</topic><topic>Lung - blood supply</topic><topic>Lung - diagnostic imaging</topic><topic>Lung - radiation effects</topic><topic>Lung Neoplasms - blood</topic><topic>Lung Neoplasms - blood supply</topic><topic>Lung Neoplasms - diagnostic imaging</topic><topic>Lung Neoplasms - genetics</topic><topic>Lung Neoplasms - radiotherapy</topic><topic>Male</topic><topic>Middle Aged</topic><topic>Neoplasm Proteins - blood</topic><topic>Neoplasm Proteins - genetics</topic><topic>Polymorphism, Single Nucleotide</topic><topic>Promoter Regions, Genetic - genetics</topic><topic>Radiation Injuries - blood</topic><topic>Radiation Injuries - genetics</topic><topic>Radiation Injuries - physiopathology</topic><topic>Radiation sensitivity</topic><topic>Radiation Tolerance - genetics</topic><topic>Radiology</topic><topic>Radiotherapy Dosage</topic><topic>Sequence Analysis, DNA - methods</topic><topic>Single nucleotide polymorphism</topic><topic>Single photon emission computed tomography</topic><topic>Statistics, Nonparametric</topic><topic>Tomography, Emission-Computed, Single-Photon</topic><topic>Transforming Growth Factor beta1 - blood</topic><topic>Transforming Growth Factor beta1 - genetics</topic><topic>Transforming growth factor β1</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Kelsey, Chris R., M.D</creatorcontrib><creatorcontrib>Jackson, Lauren, B.S</creatorcontrib><creatorcontrib>Langdon, Scott, Ph.D</creatorcontrib><creatorcontrib>Owzar, Kouros, Ph.D</creatorcontrib><creatorcontrib>Hubbs, Jessica, M.S</creatorcontrib><creatorcontrib>Vujaskovic, Zeljko, M.D., Ph.D</creatorcontrib><creatorcontrib>Das, Shiva, Ph.D</creatorcontrib><creatorcontrib>Marks, Lawrence B., M.D</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><jtitle>International journal of radiation oncology, biology, physics</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Kelsey, Chris R., M.D</au><au>Jackson, Lauren, B.S</au><au>Langdon, Scott, Ph.D</au><au>Owzar, Kouros, Ph.D</au><au>Hubbs, Jessica, M.S</au><au>Vujaskovic, Zeljko, M.D., Ph.D</au><au>Das, Shiva, Ph.D</au><au>Marks, Lawrence B., M.D</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>A Polymorphism Within the Promoter of the TGFβ1 Gene Is Associated With Radiation Sensitivity Using an Objective Radiologic Endpoint</atitle><jtitle>International journal of radiation oncology, biology, physics</jtitle><addtitle>Int J Radiat Oncol Biol Phys</addtitle><date>2012-02-01</date><risdate>2012</risdate><volume>82</volume><issue>2</issue><spage>e247</spage><epage>e255</epage><pages>e247-e255</pages><issn>0360-3016</issn><eissn>1879-355X</eissn><abstract>Purpose To evaluate whether single nucleotide polymorphisms (SNPs) in the transforming growth factor-β1 ( TGFβ1 ) gene are associated with radiation sensitivity using an objective radiologic endpoint. Methods and Materials Preradiation therapy and serial postradiation therapy single photon emission computed tomography (SPECT) lung perfusion scans were obtained in patients undergoing treatment for lung cancer. Serial blood samples were obtained to measure circulating levels of TGFβ1. Changes in regional perfusion were related to regional radiation dose yielding a patient-specific dose–response curve, reflecting the patient’s inherent sensitivity to radiation therapy. Six TGFβ1 SNPs (-988, -800, -509, 869, 941, and 1655) were assessed using high-resolution melting assays and DNA sequencing. The association between genotype and slope of the dose–response curve, and genotype and TGFβ1 ratio (4-week/preradiation therapy), was analyzed using the Kruskal-Wallis test. Results 39 white patients with preradiation therapy and ≥6-month postradiation therapy SPECT scans and blood samples were identified. Increasing slope of the dose–response curve was associated with the C(-509)T SNP ( p = 0.035), but not the other analyzed SNPs. This SNP was also associated with higher TGFβ1 ratios. Conclusions This study suggests that a polymorphism within the promoter of the TGFβ1 gene is associated with increased radiation sensitivity (defined objectively by dose-dependent changes in SPECT lung perfusion).</abstract><cop>United States</cop><pub>Elsevier Inc</pub><pmid>21605940</pmid><doi>10.1016/j.ijrobp.2011.02.064</doi></addata></record> |
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| subjects | Aged Aged, 80 and over Dose-Response Relationship, Radiation Female Genotype Hematology, Oncology and Palliative Medicine Humans Lung - blood supply Lung - diagnostic imaging Lung - radiation effects Lung Neoplasms - blood Lung Neoplasms - blood supply Lung Neoplasms - diagnostic imaging Lung Neoplasms - genetics Lung Neoplasms - radiotherapy Male Middle Aged Neoplasm Proteins - blood Neoplasm Proteins - genetics Polymorphism, Single Nucleotide Promoter Regions, Genetic - genetics Radiation Injuries - blood Radiation Injuries - genetics Radiation Injuries - physiopathology Radiation sensitivity Radiation Tolerance - genetics Radiology Radiotherapy Dosage Sequence Analysis, DNA - methods Single nucleotide polymorphism Single photon emission computed tomography Statistics, Nonparametric Tomography, Emission-Computed, Single-Photon Transforming Growth Factor beta1 - blood Transforming Growth Factor beta1 - genetics Transforming growth factor β1 |
| title | A Polymorphism Within the Promoter of the TGFβ1 Gene Is Associated With Radiation Sensitivity Using an Objective Radiologic Endpoint |
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