Genetic Variants in Inflammation-Related Genes Are Associated with Radiation-Induced Toxicity Following Treatment for Non-Small Cell Lung Cancer
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{"title"=>"Genetic variants in inflammation-related genes are associated with radiation-induced toxicity following treatment for non-small cell lung cancer", "type"=>"journal", "authors"=>[{"first_name"=>"Michelle A T", "last_name"=>"Hildebrandt", "scopus_author_id"=>"8875840300"}, {"first_name"=>"Ritsuko", "last_name"=>"Komaki", "scopus_author_id"=>"35375100800"}, {"first_name"=>"Zhongxing", "last_name"=>"Liao", "scopus_author_id"=>"7203032871"}, {"first_name"=>"Jian", "last_name"=>"Gu", "scopus_author_id"=>"34569668000"}, {"first_name"=>"Joe Y.", "last_name"=>"Chang", "scopus_author_id"=>"13310000400"}, {"first_name"=>"Yuanqing", "last_name"=>"Ye", "scopus_author_id"=>"11140209100"}, {"first_name"=>"Charles", "last_name"=>"Lu", "scopus_author_id"=>"35318026800"}, {"first_name"=>"David J.", "last_name"=>"Stewart", "scopus_author_id"=>"7403643687"}, {"first_name"=>"John D.", "last_name"=>"Minna", "scopus_author_id"=>"35380041500"}, {"first_name"=>"Jack A.", "last_name"=>"Roth", "scopus_author_id"=>"7404379856"}, {"first_name"=>"Scott M.", "last_name"=>"Lippman", "scopus_author_id"=>"35371332900"}, {"first_name"=>"James D.", "last_name"=>"Cox", "scopus_author_id"=>"36014329700"}, {"first_name"=>"Waun Ki", "last_name"=>"Hong", "scopus_author_id"=>"35378571700"}, {"first_name"=>"Margaret R.", "last_name"=>"Spitz", "scopus_author_id"=>"7103219690"}, {"first_name"=>"Xifeng", "last_name"=>"Wu", "scopus_author_id"=>"8236942400"}], "year"=>2010, "source"=>"PLoS ONE", "identifiers"=>{"pmid"=>"20811626", "doi"=>"10.1371/journal.pone.0012402", "sgr"=>"77957867311", "isbn"=>"1932-6203 (Electronic)\\r1932-6203 (Linking)", "scopus"=>"2-s2.0-77957867311", "issn"=>"19326203", "pui"=>"359754308"}, "id"=>"70656645-43f6-3420-8fca-928724dbd31f", "abstract"=>"Treatment of non-small cell lung cancer (NSCLC) with radiotherapy or chemoradiotherapy is often accompanied by the development of esophagitis and pneumonitis. Identifying patients who might be at increased risk for normal tissue toxicity would help in determination of the optimal radiation dose to avoid these events. We profiled 59 single nucleotide polymorphisms (SNPs) from 37 inflammation-related genes in 173 NSCLC patients with stage IIIA/IIIB (dry) disease who were treated with definitive radiation or chemoradiation. For esophagitis risk, nine SNPs were associated with a 1.5- to 4-fold increase in risk, including three PTGS2 (COX2) variants: rs20417 (HR:1.93, 95% CI:1.10-3.39), rs5275 (HR:1.58, 95% CI:1.09-2.27), and rs689470 (HR:3.38, 95% CI:1.09-10.49). Significantly increased risk of pneumonitis was observed for patients with genetic variation in the proinflammatory genes IL1A, IL8, TNF, TNFRSF1B, and MIF. In contrast, NOS3:rs1799983 displayed a protective effect with a 45% reduction in pneumonitis risk (HR:0.55, 95% CI:0.31-0.96). Pneumonitis risk was also modulated by polymorphisms in anti-inflammatory genes, including genetic variation in IL13. rs20541 and rs180925 each resulted in increased risk (HR:2.95, 95% CI:1.14-7.63 and HR:3.23, 95% CI:1.03-10.18, respectively). The cumulative effect of these SNPs on risk was dose-dependent, as evidenced by a significantly increased risk of either toxicity with an increasing number of risk genotypes (P<0.001). These results suggest that genetic variations among inflammation pathway genes may modulate the development of radiation-induced toxicity and, ultimately, help in identifying patients who are at an increased likelihood for such events.", "link"=>"http://www.mendeley.com/research/genetic-variants-inflammationrelated-genes-associated-radiationinduced-toxicity-following-treatment-2", "reader_count"=>27, "reader_count_by_academic_status"=>{"Professor > Associate Professor"=>2, "Researcher"=>6, "Student > Doctoral Student"=>1, "Student > Ph. D. Student"=>8, "Other"=>3, "Student > Master"=>3, "Student > Bachelor"=>4}, "reader_count_by_user_role"=>{"Professor > Associate Professor"=>2, "Researcher"=>6, "Student > Doctoral Student"=>1, "Student > Ph. D. Student"=>8, "Other"=>3, "Student > Master"=>3, "Student > Bachelor"=>4}, "reader_count_by_subject_area"=>{"Unspecified"=>1, "Biochemistry, Genetics and Molecular Biology"=>2, "Agricultural and Biological Sciences"=>10, "Medicine and Dentistry"=>13, "Chemistry"=>1}, "reader_count_by_subdiscipline"=>{"Medicine and Dentistry"=>{"Medicine and Dentistry"=>13}, "Chemistry"=>{"Chemistry"=>1}, "Agricultural and Biological Sciences"=>{"Agricultural and Biological Sciences"=>10}, "Biochemistry, Genetics and Molecular Biology"=>{"Biochemistry, Genetics and Molecular Biology"=>2}, "Unspecified"=>{"Unspecified"=>1}}, "reader_count_by_country"=>{"Brazil"=>1, "Spain"=>2}, "group_count"=>1}

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Figshare

  • {"files"=>["https://ndownloader.figshare.com/files/833834"], "description"=>"<p>(<b>A</b>) Kaplan-Meier curves of freedom from grade >2 esophagitis following radiation therapy by IL10:rs1800872 genotypes. Numbers in parentheses are the number of patients with toxicity over the total number of patients; time is median event-free duration in months. (<b>B</b>) Kaplan-Meier curves of overall survival following radiation therapy by IL10:rs1800872 genotypes. Numbers in parentheses are the number of patients alive over the total number of patients; time is median survival time in months.</p>", "links"=>[], "tags"=>["esophagitis"], "article_id"=>504192, "categories"=>["Cancer", "Genetics"], "users"=>["Michelle A. T. Hildebrandt", "Ritsuko Komaki", "Zhongxing Liao", "Jian Gu", "Joe Y. Chang", "Yuanqing Ye", "Charles Lu", "David J. Stewart", "John D. Minna", "Jack A. Roth", "Scott M. Lippman", "James D. Cox", "Waun Ki Hong", "Margaret R. Spitz", "Xifeng Wu"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0012402.g002", "stats"=>{"downloads"=>0, "page_views"=>8, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Relationship_between_esophagitis_and_overall_survival_/504192", "title"=>"Relationship between esophagitis and overall survival.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-02-20 23:48:16"}
  • {"files"=>["https://ndownloader.figshare.com/files/833901"], "description"=>"<p>*adjusted for age, gender, pack years, clinical stage, performance status, treatment regimen,</p><p>radiation type, and radiation dosage<b>.</b></p><p><sup>#</sup>unfavorable genotypes: IL6:rs1800795, IL16:rs11556218, TNF:rs1799724, PTGS2:rs20417.</p><p>PTGS2:rs5275, PTGS2:rs689470, IL4R:rs1801275, IL10:rs1800872, IL10RA:rs3135932.</p><p>IL1B:rs16944, IL2RB:rs228942, IL8:rs4073, IL10RB:rs2834167, IL13:rs1800925, NOS2:rs2297518.</p>&<p>unfavorable genotypes: IL1A:rs1800587, IL8:rs4073, TNF:rs1799724, TNFRSF1B:rs1061622.</p><p>MIF:rs7555622, IL4:rs2243250, IL4R:rs2070874, IL13:rs10800925, IL13:rs20541, NOS3:rs1799983, NFKBIA:rs1799983.</p>", "links"=>[], "tags"=>["unfavorable", "genotypes", "radiation-induced", "toxicity"], "article_id"=>504256, "categories"=>["Cancer", "Genetics"], "users"=>["Michelle A. T. Hildebrandt", "Ritsuko Komaki", "Zhongxing Liao", "Jian Gu", "Joe Y. Chang", "Yuanqing Ye", "Charles Lu", "David J. Stewart", "John D. Minna", "Jack A. Roth", "Scott M. Lippman", "James D. Cox", "Waun Ki Hong", "Margaret R. Spitz", "Xifeng Wu"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0012402.t003", "stats"=>{"downloads"=>3, "page_views"=>9, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Cumulative_effect_of_unfavorable_genotypes_and_radiation_induced_toxicity_risk_/504256", "title"=>"Cumulative effect of unfavorable genotypes and radiation-induced toxicity risk.", "pos_in_sequence"=>0, "defined_type"=>3, "published_date"=>"2013-02-20 23:48:38"}
  • {"files"=>["https://ndownloader.figshare.com/files/833752"], "description"=>"<p>Kaplan-Meier curves of freedom from (<b>A</b>) grade >2 esophagitis or (<b>B</b>) grade >2 pneumonitis following radiation therapy. Numbers in parentheses are the number of patients with toxicity over the total number of patients; time is median event-free duration in months.</p>", "links"=>[], "tags"=>["unfavorable", "genotypes", "inflammation-related"], "article_id"=>504098, "categories"=>["Cancer", "Genetics"], "users"=>["Michelle A. T. Hildebrandt", "Ritsuko Komaki", "Zhongxing Liao", "Jian Gu", "Joe Y. Chang", "Yuanqing Ye", "Charles Lu", "David J. Stewart", "John D. Minna", "Jack A. Roth", "Scott M. Lippman", "James D. Cox", "Waun Ki Hong", "Margaret R. Spitz", "Xifeng Wu"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0012402.g001", "stats"=>{"downloads"=>1, "page_views"=>6, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Event_free_survival_by_number_of_unfavorable_genotypes_in_inflammation_related_genes_/504098", "title"=>"Event-free survival by number of unfavorable genotypes in inflammation-related genes.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-02-20 23:47:48"}
  • {"files"=>["https://ndownloader.figshare.com/files/834049"], "description"=>"<p>*FR: flanking region, UTR: untranslated region.</p>", "links"=>[], "tags"=>["nucleotide", "polymorphism"], "article_id"=>504405, "categories"=>["Cancer", "Genetics"], "users"=>["Michelle A. T. Hildebrandt", "Ritsuko Komaki", "Zhongxing Liao", "Jian Gu", "Joe Y. Chang", "Yuanqing Ye", "Charles Lu", "David J. Stewart", "John D. Minna", "Jack A. Roth", "Scott M. Lippman", "James D. Cox", "Waun Ki Hong", "Margaret R. Spitz", "Xifeng Wu"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0012402.t005", "stats"=>{"downloads"=>18, "page_views"=>3, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Inflammation_single_nucleotide_polymorphism_characteristics_/504405", "title"=>"Inflammation single nucleotide polymorphism characteristics.", "pos_in_sequence"=>0, "defined_type"=>3, "published_date"=>"2013-02-20 23:49:25"}
  • {"files"=>["https://ndownloader.figshare.com/files/833948"], "description"=>"<p>*adjusted for age, gender, pack years, clinical stage, performance status, treatment regimen, radiation type, and radiation dosage.</p>", "links"=>[], "tags"=>["snps"], "article_id"=>504310, "categories"=>["Cancer", "Genetics"], "users"=>["Michelle A. T. Hildebrandt", "Ritsuko Komaki", "Zhongxing Liao", "Jian Gu", "Joe Y. Chang", "Yuanqing Ye", "Charles Lu", "David J. Stewart", "John D. Minna", "Jack A. Roth", "Scott M. Lippman", "James D. Cox", "Waun Ki Hong", "Margaret R. Spitz", "Xifeng Wu"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0012402.t002", "stats"=>{"downloads"=>0, "page_views"=>5, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Inflammation_related_SNPs_and_risk_of_esophagitis_/504310", "title"=>"Inflammation-related SNPs and risk of esophagitis.", "pos_in_sequence"=>0, "defined_type"=>3, "published_date"=>"2013-02-20 23:48:54"}
  • {"files"=>["https://ndownloader.figshare.com/files/834000"], "description"=>"<p>Patient characteristics.</p>", "links"=>[], "tags"=>["oncology", "genetics and genomics/genetics of the immune system", "oncology/lung cancer", "oncology/oncology agents"], "article_id"=>504353, "categories"=>["Cancer", "Genetics"], "users"=>["Michelle A. T. Hildebrandt", "Ritsuko Komaki", "Zhongxing Liao", "Jian Gu", "Joe Y. Chang", "Yuanqing Ye", "Charles Lu", "David J. Stewart", "John D. Minna", "Jack A. Roth", "Scott M. Lippman", "James D. Cox", "Waun Ki Hong", "Margaret R. Spitz", "Xifeng Wu"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0012402.t001", "stats"=>{"downloads"=>1, "page_views"=>8, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Patient_characteristics_/504353", "title"=>"Patient characteristics.", "pos_in_sequence"=>0, "defined_type"=>3, "published_date"=>"2013-02-20 23:49:08"}
  • {"files"=>["https://ndownloader.figshare.com/files/834104"], "description"=>"<p>*adjusted for age, gender, pack years, clinical stage, performance status, treatment regimen, radiation type, and radiation dosage.</p>", "links"=>[], "tags"=>["snps"], "article_id"=>504462, "categories"=>["Cancer", "Genetics"], "users"=>["Michelle A. T. Hildebrandt", "Ritsuko Komaki", "Zhongxing Liao", "Jian Gu", "Joe Y. Chang", "Yuanqing Ye", "Charles Lu", "David J. Stewart", "John D. Minna", "Jack A. Roth", "Scott M. Lippman", "James D. Cox", "Waun Ki Hong", "Margaret R. Spitz", "Xifeng Wu"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0012402.t004", "stats"=>{"downloads"=>0, "page_views"=>4, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Inflammation_related_SNPs_and_risk_of_pneumonitis_/504462", "title"=>"Inflammation-related SNPs and risk of pneumonitis.", "pos_in_sequence"=>0, "defined_type"=>3, "published_date"=>"2013-02-20 23:49:40"}

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