Genome-wide association study of genetic variations associated with treatment failure after intravesical bacillus Calmette–Guérin therapy for non-muscle invasive bladder cancer
Bacillus Calmette–Guérin (BCG) instillation is a key therapy to manage non-muscle invasive bladder cancer (NMIBC). However, intravesical BCG therapy fails in approximately half of the patients, leading to recurrence and progression. We aimed to reveal the genetic variations associated with treatment...
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| Veröffentlicht in: | Cancer Immunology, Immunotherapy Immunotherapy, 2020-07, Vol.69 (7), p.1155-1163 |
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| creator | Shiota, Masaki Fujimoto, Naohiro Yamamoto, Yoshiaki Takeuchi, Ario Tatsugami, Katsunori Uchiumi, Takeshi Matsuyama, Hideyasu Eto, Masatoshi |
| description | Bacillus Calmette–Guérin (BCG) instillation is a key therapy to manage non-muscle invasive bladder cancer (NMIBC). However, intravesical BCG therapy fails in approximately half of the patients, leading to recurrence and progression. We aimed to reveal the genetic variations associated with treatment failure after intravesical BCG therapy for NMIBC. This study included 91 Japanese patients treated with BCG instillation for NMIBC. Genomic DNA was obtained from patient whole-blood samples, and a genome-wide association study and genotyping for target regions were performed. The association between genetic variation and treatment failure was analyzed by genome-wide association in 44 patients as the discovery cohort. As a validation study, candidate single nucleotide polymorphisms (SNPs) were examined among 47 patients in another cohort. The genome-wide association study indicated 19 candidate SNPs (rs1607282, rs7825442, rs1319325, rs3738088, rs4250, rs11894207, rs161448, rs2764326, rs2814707, rs3787194, rs58081719, rs3095966, rs73520681, rs16877113, rs16887173, rs10269584, rs11772249, rs118137814, and rs61094339) associated with BCG failure. Following the cumulative analysis of candidate SNPs, 2-gene (rs73520681 and rs61094339) and 4-gene (rs4250, rs11894207, rs73520681, and rs61094339) models successfully predicted treatment failure after intravesical BCG therapy. This study showed that several SNPs were possibly associated with outcome after intravesical BCG therapy in a Japanese population with NMIBC. The cumulative models of these SNPs may have value in clinical applications, although this should be confirmed in future studies. |
| doi_str_mv | 10.1007/s00262-020-02533-8 |
| format | Article |
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However, intravesical BCG therapy fails in approximately half of the patients, leading to recurrence and progression. We aimed to reveal the genetic variations associated with treatment failure after intravesical BCG therapy for NMIBC. This study included 91 Japanese patients treated with BCG instillation for NMIBC. Genomic DNA was obtained from patient whole-blood samples, and a genome-wide association study and genotyping for target regions were performed. The association between genetic variation and treatment failure was analyzed by genome-wide association in 44 patients as the discovery cohort. As a validation study, candidate single nucleotide polymorphisms (SNPs) were examined among 47 patients in another cohort. The genome-wide association study indicated 19 candidate SNPs (rs1607282, rs7825442, rs1319325, rs3738088, rs4250, rs11894207, rs161448, rs2764326, rs2814707, rs3787194, rs58081719, rs3095966, rs73520681, rs16877113, rs16887173, rs10269584, rs11772249, rs118137814, and rs61094339) associated with BCG failure. Following the cumulative analysis of candidate SNPs, 2-gene (rs73520681 and rs61094339) and 4-gene (rs4250, rs11894207, rs73520681, and rs61094339) models successfully predicted treatment failure after intravesical BCG therapy. This study showed that several SNPs were possibly associated with outcome after intravesical BCG therapy in a Japanese population with NMIBC. The cumulative models of these SNPs may have value in clinical applications, although this should be confirmed in future studies.</description><identifier>ISSN: 0340-7004</identifier><identifier>EISSN: 1432-0851</identifier><identifier>DOI: 10.1007/s00262-020-02533-8</identifier><identifier>PMID: 32123936</identifier><language>eng</language><publisher>Berlin/Heidelberg: Springer Berlin Heidelberg</publisher><subject>Administration, Intravesical ; Aged ; Bacillus Calmette-Guerin vaccine ; BCG ; BCG Vaccine - administration & dosage ; Biomarkers, Tumor - genetics ; Bladder cancer ; Cancer Research ; Disease Progression ; Female ; Follow-Up Studies ; Genetic diversity ; Genome-wide association studies ; Genome-Wide Association Study ; Genomes ; Genotyping ; Humans ; Immunology ; Invasiveness ; Male ; Medicine ; Medicine & Public Health ; Middle Aged ; Oncology ; Original ; Original Article ; Patients ; Polymorphism, Single Nucleotide ; Retrospective Studies ; Single-nucleotide polymorphism ; Survival Rate ; Therapeutic applications ; Treatment Failure ; Urinary Bladder Neoplasms - drug therapy ; Urinary Bladder Neoplasms - genetics ; Urinary Bladder Neoplasms - pathology</subject><ispartof>Cancer Immunology, Immunotherapy, 2020-07, Vol.69 (7), p.1155-1163</ispartof><rights>Springer-Verlag GmbH Germany, part of Springer Nature 2020</rights><rights>Springer-Verlag GmbH Germany, part of Springer Nature 2020.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c431t-d1e71d1763234d4b76b8408b02e85b89d4cc8e9960819729ef5ea87d026e94533</citedby><cites>FETCH-LOGICAL-c431t-d1e71d1763234d4b76b8408b02e85b89d4cc8e9960819729ef5ea87d026e94533</cites><orcidid>0000-0002-3306-4858</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC11027686/pdf/$$EPDF$$P50$$Gpubmedcentral$$H</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC11027686/$$EHTML$$P50$$Gpubmedcentral$$H</linktohtml><link.rule.ids>230,314,724,777,781,882,27905,27906,41469,42538,51300,53772,53774</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/32123936$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Shiota, Masaki</creatorcontrib><creatorcontrib>Fujimoto, Naohiro</creatorcontrib><creatorcontrib>Yamamoto, Yoshiaki</creatorcontrib><creatorcontrib>Takeuchi, Ario</creatorcontrib><creatorcontrib>Tatsugami, Katsunori</creatorcontrib><creatorcontrib>Uchiumi, Takeshi</creatorcontrib><creatorcontrib>Matsuyama, Hideyasu</creatorcontrib><creatorcontrib>Eto, Masatoshi</creatorcontrib><title>Genome-wide association study of genetic variations associated with treatment failure after intravesical bacillus Calmette–Guérin therapy for non-muscle invasive bladder cancer</title><title>Cancer Immunology, Immunotherapy</title><addtitle>Cancer Immunol Immunother</addtitle><addtitle>Cancer Immunol Immunother</addtitle><description>Bacillus Calmette–Guérin (BCG) instillation is a key therapy to manage non-muscle invasive bladder cancer (NMIBC). However, intravesical BCG therapy fails in approximately half of the patients, leading to recurrence and progression. We aimed to reveal the genetic variations associated with treatment failure after intravesical BCG therapy for NMIBC. This study included 91 Japanese patients treated with BCG instillation for NMIBC. Genomic DNA was obtained from patient whole-blood samples, and a genome-wide association study and genotyping for target regions were performed. The association between genetic variation and treatment failure was analyzed by genome-wide association in 44 patients as the discovery cohort. As a validation study, candidate single nucleotide polymorphisms (SNPs) were examined among 47 patients in another cohort. 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The cumulative models of these SNPs may have value in clinical applications, although this should be confirmed in future studies.</description><subject>Administration, Intravesical</subject><subject>Aged</subject><subject>Bacillus Calmette-Guerin vaccine</subject><subject>BCG</subject><subject>BCG Vaccine - administration & dosage</subject><subject>Biomarkers, Tumor - genetics</subject><subject>Bladder cancer</subject><subject>Cancer Research</subject><subject>Disease Progression</subject><subject>Female</subject><subject>Follow-Up Studies</subject><subject>Genetic diversity</subject><subject>Genome-wide association studies</subject><subject>Genome-Wide Association Study</subject><subject>Genomes</subject><subject>Genotyping</subject><subject>Humans</subject><subject>Immunology</subject><subject>Invasiveness</subject><subject>Male</subject><subject>Medicine</subject><subject>Medicine & Public Health</subject><subject>Middle Aged</subject><subject>Oncology</subject><subject>Original</subject><subject>Original Article</subject><subject>Patients</subject><subject>Polymorphism, Single Nucleotide</subject><subject>Retrospective Studies</subject><subject>Single-nucleotide polymorphism</subject><subject>Survival Rate</subject><subject>Therapeutic applications</subject><subject>Treatment Failure</subject><subject>Urinary Bladder Neoplasms - 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administration & dosage</topic><topic>Biomarkers, Tumor - genetics</topic><topic>Bladder cancer</topic><topic>Cancer Research</topic><topic>Disease Progression</topic><topic>Female</topic><topic>Follow-Up Studies</topic><topic>Genetic diversity</topic><topic>Genome-wide association studies</topic><topic>Genome-Wide Association Study</topic><topic>Genomes</topic><topic>Genotyping</topic><topic>Humans</topic><topic>Immunology</topic><topic>Invasiveness</topic><topic>Male</topic><topic>Medicine</topic><topic>Medicine & Public Health</topic><topic>Middle Aged</topic><topic>Oncology</topic><topic>Original</topic><topic>Original Article</topic><topic>Patients</topic><topic>Polymorphism, Single Nucleotide</topic><topic>Retrospective Studies</topic><topic>Single-nucleotide polymorphism</topic><topic>Survival Rate</topic><topic>Therapeutic applications</topic><topic>Treatment Failure</topic><topic>Urinary Bladder Neoplasms - drug therapy</topic><topic>Urinary Bladder Neoplasms - genetics</topic><topic>Urinary Bladder Neoplasms - pathology</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Shiota, Masaki</creatorcontrib><creatorcontrib>Fujimoto, Naohiro</creatorcontrib><creatorcontrib>Yamamoto, Yoshiaki</creatorcontrib><creatorcontrib>Takeuchi, Ario</creatorcontrib><creatorcontrib>Tatsugami, Katsunori</creatorcontrib><creatorcontrib>Uchiumi, Takeshi</creatorcontrib><creatorcontrib>Matsuyama, Hideyasu</creatorcontrib><creatorcontrib>Eto, Masatoshi</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>ProQuest Central (Corporate)</collection><collection>Immunology Abstracts</collection><collection>Health & Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Medical Database (Alumni Edition)</collection><collection>ProQuest Pharma Collection</collection><collection>Public Health Database</collection><collection>ProQuest SciTech Collection</collection><collection>ProQuest Natural Science Collection</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>Biological Science Collection</collection><collection>ProQuest Central</collection><collection>Natural Science Collection</collection><collection>ProQuest One Community College</collection><collection>ProQuest Central Korea</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>ProQuest Central Student</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>SciTech Premium Collection</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>ProQuest Biological Science Collection</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>Medical Database</collection><collection>Biological Science 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>PubMed Central (Full Participant titles)</collection><jtitle>Cancer Immunology, Immunotherapy</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Shiota, Masaki</au><au>Fujimoto, Naohiro</au><au>Yamamoto, Yoshiaki</au><au>Takeuchi, Ario</au><au>Tatsugami, Katsunori</au><au>Uchiumi, Takeshi</au><au>Matsuyama, Hideyasu</au><au>Eto, Masatoshi</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Genome-wide association study of genetic variations associated with treatment failure after intravesical bacillus Calmette–Guérin therapy for non-muscle invasive bladder cancer</atitle><jtitle>Cancer Immunology, Immunotherapy</jtitle><stitle>Cancer Immunol Immunother</stitle><addtitle>Cancer Immunol Immunother</addtitle><date>2020-07-01</date><risdate>2020</risdate><volume>69</volume><issue>7</issue><spage>1155</spage><epage>1163</epage><pages>1155-1163</pages><issn>0340-7004</issn><eissn>1432-0851</eissn><abstract>Bacillus Calmette–Guérin (BCG) instillation is a key therapy to manage non-muscle invasive bladder cancer (NMIBC). However, intravesical BCG therapy fails in approximately half of the patients, leading to recurrence and progression. We aimed to reveal the genetic variations associated with treatment failure after intravesical BCG therapy for NMIBC. This study included 91 Japanese patients treated with BCG instillation for NMIBC. Genomic DNA was obtained from patient whole-blood samples, and a genome-wide association study and genotyping for target regions were performed. The association between genetic variation and treatment failure was analyzed by genome-wide association in 44 patients as the discovery cohort. As a validation study, candidate single nucleotide polymorphisms (SNPs) were examined among 47 patients in another cohort. The genome-wide association study indicated 19 candidate SNPs (rs1607282, rs7825442, rs1319325, rs3738088, rs4250, rs11894207, rs161448, rs2764326, rs2814707, rs3787194, rs58081719, rs3095966, rs73520681, rs16877113, rs16887173, rs10269584, rs11772249, rs118137814, and rs61094339) associated with BCG failure. Following the cumulative analysis of candidate SNPs, 2-gene (rs73520681 and rs61094339) and 4-gene (rs4250, rs11894207, rs73520681, and rs61094339) models successfully predicted treatment failure after intravesical BCG therapy. This study showed that several SNPs were possibly associated with outcome after intravesical BCG therapy in a Japanese population with NMIBC. The cumulative models of these SNPs may have value in clinical applications, although this should be confirmed in future studies.</abstract><cop>Berlin/Heidelberg</cop><pub>Springer Berlin Heidelberg</pub><pmid>32123936</pmid><doi>10.1007/s00262-020-02533-8</doi><tpages>9</tpages><orcidid>https://orcid.org/0000-0002-3306-4858</orcidid></addata></record> |
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| source | MEDLINE; Springer Nature - Complete Springer Journals; PubMed Central |
| subjects | Administration, Intravesical Aged Bacillus Calmette-Guerin vaccine BCG BCG Vaccine - administration & dosage Biomarkers, Tumor - genetics Bladder cancer Cancer Research Disease Progression Female Follow-Up Studies Genetic diversity Genome-wide association studies Genome-Wide Association Study Genomes Genotyping Humans Immunology Invasiveness Male Medicine Medicine & Public Health Middle Aged Oncology Original Original Article Patients Polymorphism, Single Nucleotide Retrospective Studies Single-nucleotide polymorphism Survival Rate Therapeutic applications Treatment Failure Urinary Bladder Neoplasms - drug therapy Urinary Bladder Neoplasms - genetics Urinary Bladder Neoplasms - pathology |
| title | Genome-wide association study of genetic variations associated with treatment failure after intravesical bacillus Calmette–Guérin therapy for non-muscle invasive bladder cancer |
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