The SNP rs6500843 in 16p13.3 is associated with survival specifically among chemotherapy-treated breast cancer patients
We have utilized a two-stage study design to search for SNPs associated with the survival of breast cancer patients treated with adjuvant chemotherapy. Our initial GWS data set consisted of 805 Finnish breast cancer cases (360 treated with adjuvant chemotherapy). The top 39 SNPs from this stage were...
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| Veröffentlicht in: | Oncotarget 2015-04, Vol.6 (10), p.7390-407 |
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| creator | Fagerholm, Rainer Schmidt, Marjanka K Khan, Sofia Rafiq, Sajjad Tapper, William Aittomäki, Kristiina Greco, Dario Heikkinen, Tuomas Muranen, Taru A Fasching, Peter A Janni, Wolfgang Weinshilboum, Richard Loehberg, Christian R Hopper, John L Southey, Melissa C Keeman, Renske Lindblom, Annika Margolin, Sara Mannermaa, Arto Kataja, Vesa Chenevix-Trench, Georgia kConFab Investigators Lambrechts, Diether Wildiers, Hans Chang-Claude, Jenny Seibold, Petra Couch, Fergus J Olson, Janet E Andrulis, Irene L Knight, Julia A García-Closas, Montserrat Figueroa, Jonine Hooning, Maartje J Jager, Agnes Shah, Mitul Perkins, Barbara J Luben, Robert Hamann, Ute Kabisch, Maria Czene, Kamila Hall, Per Easton, Douglas F Pharoah, Paul D.P Liu, Jianjun Eccles, Diana Blomqvist, Carl Nevanlinna, Heli |
| description | We have utilized a two-stage study design to search for SNPs associated with the survival of breast cancer patients treated with adjuvant chemotherapy. Our initial GWS data set consisted of 805 Finnish breast cancer cases (360 treated with adjuvant chemotherapy). The top 39 SNPs from this stage were analyzed in three independent data sets: iCOGS (n=6720 chemotherapy-treated cases), SUCCESS-A (n=3596), and POSH (n=518). Two SNPs were successfully validated: rs6500843 (any chemotherapy; per-allele HR 1.16, 95% C.I. 1.08-1.26, p=0.0001, p(adjusted)=0.0091), and rs11155012 (anthracycline therapy; per-allele HR 1.21, 95% C.I. 1.08-1.35, p=0.0010, p(adjusted)=0.0270). The SNP rs6500843 was found to specifically interact with adjuvant chemotherapy, independently of standard prognostic markers (p(interaction)=0.0009), with the rs6500843-GG genotype corresponding to the highest hazard among chemotherapy-treated cases (HR 1.47, 95% C.I. 1.20-1.80). Upon trans-eQTL analysis of public microarray data, the rs6500843 locus was found to associate with the expression of a group of genes involved in cell cycle control, notably AURKA, the expression of which also exhibited differential prognostic value between chemotherapy-treated and untreated cases in our analysis of microarray data. Based on previously published information, we propose that the eQTL genes may be connected to the rs6500843 locus via a RBFOX1-FOXM1 -mediated regulatory pathway. |
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Our initial GWS data set consisted of 805 Finnish breast cancer cases (360 treated with adjuvant chemotherapy). The top 39 SNPs from this stage were analyzed in three independent data sets: iCOGS (n=6720 chemotherapy-treated cases), SUCCESS-A (n=3596), and POSH (n=518). Two SNPs were successfully validated: rs6500843 (any chemotherapy; per-allele HR 1.16, 95% C.I. 1.08-1.26, p=0.0001, p(adjusted)=0.0091), and rs11155012 (anthracycline therapy; per-allele HR 1.21, 95% C.I. 1.08-1.35, p=0.0010, p(adjusted)=0.0270). The SNP rs6500843 was found to specifically interact with adjuvant chemotherapy, independently of standard prognostic markers (p(interaction)=0.0009), with the rs6500843-GG genotype corresponding to the highest hazard among chemotherapy-treated cases (HR 1.47, 95% C.I. 1.20-1.80). Upon trans-eQTL analysis of public microarray data, the rs6500843 locus was found to associate with the expression of a group of genes involved in cell cycle control, notably AURKA, the expression of which also exhibited differential prognostic value between chemotherapy-treated and untreated cases in our analysis of microarray data. Based on previously published information, we propose that the eQTL genes may be connected to the rs6500843 locus via a RBFOX1-FOXM1 -mediated regulatory pathway.</description><identifier>ISSN: 1949-2553</identifier><identifier>EISSN: 1949-2553</identifier><language>eng</language><publisher>IMPACT JOURNALS LLC</publisher><ispartof>Oncotarget, 2015-04, Vol.6 (10), p.7390-407</ispartof><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,315,780,784,27858</link.rule.ids></links><search><creatorcontrib>Fagerholm, Rainer</creatorcontrib><creatorcontrib>Schmidt, Marjanka K</creatorcontrib><creatorcontrib>Khan, Sofia</creatorcontrib><creatorcontrib>Rafiq, Sajjad</creatorcontrib><creatorcontrib>Tapper, William</creatorcontrib><creatorcontrib>Aittomäki, Kristiina</creatorcontrib><creatorcontrib>Greco, Dario</creatorcontrib><creatorcontrib>Heikkinen, Tuomas</creatorcontrib><creatorcontrib>Muranen, Taru A</creatorcontrib><creatorcontrib>Fasching, Peter A</creatorcontrib><creatorcontrib>Janni, Wolfgang</creatorcontrib><creatorcontrib>Weinshilboum, Richard</creatorcontrib><creatorcontrib>Loehberg, Christian R</creatorcontrib><creatorcontrib>Hopper, John L</creatorcontrib><creatorcontrib>Southey, Melissa C</creatorcontrib><creatorcontrib>Keeman, Renske</creatorcontrib><creatorcontrib>Lindblom, Annika</creatorcontrib><creatorcontrib>Margolin, Sara</creatorcontrib><creatorcontrib>Mannermaa, Arto</creatorcontrib><creatorcontrib>Kataja, Vesa</creatorcontrib><creatorcontrib>Chenevix-Trench, Georgia</creatorcontrib><creatorcontrib>kConFab Investigators</creatorcontrib><creatorcontrib>Lambrechts, Diether</creatorcontrib><creatorcontrib>Wildiers, Hans</creatorcontrib><creatorcontrib>Chang-Claude, Jenny</creatorcontrib><creatorcontrib>Seibold, Petra</creatorcontrib><creatorcontrib>Couch, Fergus J</creatorcontrib><creatorcontrib>Olson, Janet E</creatorcontrib><creatorcontrib>Andrulis, Irene L</creatorcontrib><creatorcontrib>Knight, Julia A</creatorcontrib><creatorcontrib>García-Closas, Montserrat</creatorcontrib><creatorcontrib>Figueroa, Jonine</creatorcontrib><creatorcontrib>Hooning, Maartje J</creatorcontrib><creatorcontrib>Jager, Agnes</creatorcontrib><creatorcontrib>Shah, Mitul</creatorcontrib><creatorcontrib>Perkins, Barbara J</creatorcontrib><creatorcontrib>Luben, Robert</creatorcontrib><creatorcontrib>Hamann, Ute</creatorcontrib><creatorcontrib>Kabisch, Maria</creatorcontrib><creatorcontrib>Czene, Kamila</creatorcontrib><creatorcontrib>Hall, Per</creatorcontrib><creatorcontrib>Easton, Douglas F</creatorcontrib><creatorcontrib>Pharoah, Paul D.P</creatorcontrib><creatorcontrib>Liu, Jianjun</creatorcontrib><creatorcontrib>Eccles, Diana</creatorcontrib><creatorcontrib>Blomqvist, Carl</creatorcontrib><creatorcontrib>Nevanlinna, Heli</creatorcontrib><title>The SNP rs6500843 in 16p13.3 is associated with survival specifically among chemotherapy-treated breast cancer patients</title><title>Oncotarget</title><description>We have utilized a two-stage study design to search for SNPs associated with the survival of breast cancer patients treated with adjuvant chemotherapy. Our initial GWS data set consisted of 805 Finnish breast cancer cases (360 treated with adjuvant chemotherapy). The top 39 SNPs from this stage were analyzed in three independent data sets: iCOGS (n=6720 chemotherapy-treated cases), SUCCESS-A (n=3596), and POSH (n=518). Two SNPs were successfully validated: rs6500843 (any chemotherapy; per-allele HR 1.16, 95% C.I. 1.08-1.26, p=0.0001, p(adjusted)=0.0091), and rs11155012 (anthracycline therapy; per-allele HR 1.21, 95% C.I. 1.08-1.35, p=0.0010, p(adjusted)=0.0270). The SNP rs6500843 was found to specifically interact with adjuvant chemotherapy, independently of standard prognostic markers (p(interaction)=0.0009), with the rs6500843-GG genotype corresponding to the highest hazard among chemotherapy-treated cases (HR 1.47, 95% C.I. 1.20-1.80). Upon trans-eQTL analysis of public microarray data, the rs6500843 locus was found to associate with the expression of a group of genes involved in cell cycle control, notably AURKA, the expression of which also exhibited differential prognostic value between chemotherapy-treated and untreated cases in our analysis of microarray data. 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Diana</creatorcontrib><creatorcontrib>Blomqvist, Carl</creatorcontrib><creatorcontrib>Nevanlinna, Heli</creatorcontrib><collection>Lirias (KU Leuven Association)</collection><jtitle>Oncotarget</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Fagerholm, Rainer</au><au>Schmidt, Marjanka K</au><au>Khan, Sofia</au><au>Rafiq, Sajjad</au><au>Tapper, William</au><au>Aittomäki, Kristiina</au><au>Greco, Dario</au><au>Heikkinen, Tuomas</au><au>Muranen, Taru A</au><au>Fasching, Peter A</au><au>Janni, Wolfgang</au><au>Weinshilboum, Richard</au><au>Loehberg, Christian R</au><au>Hopper, John L</au><au>Southey, Melissa C</au><au>Keeman, Renske</au><au>Lindblom, Annika</au><au>Margolin, Sara</au><au>Mannermaa, Arto</au><au>Kataja, Vesa</au><au>Chenevix-Trench, Georgia</au><au>kConFab Investigators</au><au>Lambrechts, Diether</au><au>Wildiers, Hans</au><au>Chang-Claude, Jenny</au><au>Seibold, Petra</au><au>Couch, Fergus J</au><au>Olson, Janet E</au><au>Andrulis, Irene L</au><au>Knight, Julia A</au><au>García-Closas, Montserrat</au><au>Figueroa, Jonine</au><au>Hooning, Maartje J</au><au>Jager, Agnes</au><au>Shah, Mitul</au><au>Perkins, Barbara J</au><au>Luben, Robert</au><au>Hamann, Ute</au><au>Kabisch, Maria</au><au>Czene, Kamila</au><au>Hall, Per</au><au>Easton, Douglas F</au><au>Pharoah, Paul D.P</au><au>Liu, Jianjun</au><au>Eccles, Diana</au><au>Blomqvist, Carl</au><au>Nevanlinna, Heli</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>The SNP rs6500843 in 16p13.3 is associated with survival specifically among chemotherapy-treated breast cancer patients</atitle><jtitle>Oncotarget</jtitle><date>2015-04</date><risdate>2015</risdate><volume>6</volume><issue>10</issue><spage>7390</spage><epage>407</epage><pages>7390-407</pages><issn>1949-2553</issn><eissn>1949-2553</eissn><abstract>We have utilized a two-stage study design to search for SNPs associated with the survival of breast cancer patients treated with adjuvant chemotherapy. Our initial GWS data set consisted of 805 Finnish breast cancer cases (360 treated with adjuvant chemotherapy). The top 39 SNPs from this stage were analyzed in three independent data sets: iCOGS (n=6720 chemotherapy-treated cases), SUCCESS-A (n=3596), and POSH (n=518). Two SNPs were successfully validated: rs6500843 (any chemotherapy; per-allele HR 1.16, 95% C.I. 1.08-1.26, p=0.0001, p(adjusted)=0.0091), and rs11155012 (anthracycline therapy; per-allele HR 1.21, 95% C.I. 1.08-1.35, p=0.0010, p(adjusted)=0.0270). The SNP rs6500843 was found to specifically interact with adjuvant chemotherapy, independently of standard prognostic markers (p(interaction)=0.0009), with the rs6500843-GG genotype corresponding to the highest hazard among chemotherapy-treated cases (HR 1.47, 95% C.I. 1.20-1.80). Upon trans-eQTL analysis of public microarray data, the rs6500843 locus was found to associate with the expression of a group of genes involved in cell cycle control, notably AURKA, the expression of which also exhibited differential prognostic value between chemotherapy-treated and untreated cases in our analysis of microarray data. Based on previously published information, we propose that the eQTL genes may be connected to the rs6500843 locus via a RBFOX1-FOXM1 -mediated regulatory pathway.</abstract><pub>IMPACT JOURNALS LLC</pub><oa>free_for_read</oa></addata></record> |
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| title | The SNP rs6500843 in 16p13.3 is associated with survival specifically among chemotherapy-treated breast cancer patients |
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