Association of breast cancer risk with genetic variants showing differential allelic expression: Identification of a novel breast cancer susceptibility locus at 4q21
There are significant inter-individual differences in the levels of gene expression. Through modulation of gene expression, cis-acting variants represent an important source of phenotypic variation. Consequently, cis-regulatory SNPs associated with differential allelic expression are functional cand...
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| Veröffentlicht in: | ONCOTARGET 2016-12, Vol.7 (49), p.80140-80163 |
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| creator | Hamdi, Yosr Soucy, Penny Adoue, Véronique Michailidou, Kyriaki Canisius, Sander Lemaçon, Audrey Droit, Arnaud Andrulis, Irene L Anton-Culver, Hoda Arndt, Volker Baynes, Caroline Blomqvist, Carl Bogdanova, Natalia V Bojesen, Stig E Bolla, Manjeet K Bonanni, Bernardo Borresen-Dale, Anne-Lise Brand, Judith S Brauch, Hiltrud Brenner, Hermann Broeks, Annegien Burwinkel, Barbara Chang-Claude, Jenny Couch, Fergus J Cox, Angela Cross, Simon S Czene, Kamila Darabi, Hatef Dennis, Joe Devilee, Peter Dörk, Thilo Dos-Santos-Silva, Isabel Eriksson, Mikael Fasching, Peter A Figueroa, Jonine Flyger, Henrik García-Closas, Montserrat Giles, Graham G Goldberg, Mark S González-Neira, Anna Grenaker-Alnæs, Grethe Guénel, Pascal Haeberle, Lothar Haiman, Christopher A Hamann, Ute Hallberg, Emily Hooning, Maartje J Hopper, John L Jakubowska, Anna Jones, Michael Kabisch, Maria Kataja, Vesa Lambrechts, Diether Le Marchand, Loic Lindblom, Annika Lubinski, Jan Mannermaa, Arto Maranian, Mel Margolin, Sara Marme, Frederik Milne, Roger L Neuhausen, Susan L Nevanlinna, Heli Neven, Patrick Olswold, Curtis Peto, Julian Plaseska-Karanfilska, Dijana Pylkäs, Katri Radice, Paolo Rudolph, Anja Sawyer, Elinor J Schmidt, Marjanka K Shu, Xiao-Ou Southey, Melissa C Swerdlow, Anthony Tollenaar, Rob A E M Tomlinson, Ian Torres, Diana Truong, Thérèse Vachon, Celine Van Den Ouweland, Ans M W Wang, Qin Winqvist, Robert Zheng, Wei Benitez, Javier Chenevix-Trench, Georgia Dunning, Alison M Pharoah, Paul D P Kristensen, Vessela Hall, Per Easton, Douglas F Pastinen, Tomi Nord, Silje Simard, Jacques |
| description | There are significant inter-individual differences in the levels of gene expression. Through modulation of gene expression, cis-acting variants represent an important source of phenotypic variation. Consequently, cis-regulatory SNPs associated with differential allelic expression are functional candidates for further investigation as disease-causing variants. To investigate whether common variants associated with differential allelic expression were involved in breast cancer susceptibility, a list of genes was established on the basis of their involvement in cancer related pathways and/or mechanisms. Thereafter, using data from a genome-wide map of allelic expression associated SNPs, 313 genetic variants were selected and their association with breast cancer risk was then evaluated in 46,451 breast cancer cases and 42,599 controls of European ancestry ascertained from 41 studies participating in the Breast Cancer Association Consortium. The associations were evaluated with overall breast cancer risk and with estrogen receptor negative and positive disease. One novel breast cancer susceptibility locus on 4q21 (rs11099601) was identified (OR = 1.05, P = 5.6x10-6). rs11099601 lies in a 135 kb linkage disequilibrium block containing several genes, including, HELQ, encoding the protein HEL308 a DNA dependant ATPase and DNA Helicase involved in DNA repair, MRPS18C encoding the Mitochondrial Ribosomal Protein S18C and FAM175A (ABRAXAS), encoding a BRCA1 BRCT domain-interacting protein involved in DNA damage response and double-strand break (DSB) repair. Expression QTL analysis in breast cancer tissue showed rs11099601 to be associated with HELQ (P = 8.28x10-14), MRPS18C (P = 1.94x10-27) and FAM175A (P = 3.83x10-3), explaining about 20%, 14% and 1%, respectively of the variance inexpression of these genes in breast carcinomas. |
| doi_str_mv | 10.18632/oncotarget.12818 |
| format | Article |
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Soucy, Penny ; Adoue, Véronique ; Michailidou, Kyriaki ; Canisius, Sander ; Lemaçon, Audrey ; Droit, Arnaud ; Andrulis, Irene L ; Anton-Culver, Hoda ; Arndt, Volker ; Baynes, Caroline ; Blomqvist, Carl ; Bogdanova, Natalia V ; Bojesen, Stig E ; Bolla, Manjeet K ; Bonanni, Bernardo ; Borresen-Dale, Anne-Lise ; Brand, Judith S ; Brauch, Hiltrud ; Brenner, Hermann ; Broeks, Annegien ; Burwinkel, Barbara ; Chang-Claude, Jenny ; Couch, Fergus J ; Cox, Angela ; Cross, Simon S ; Czene, Kamila ; Darabi, Hatef ; Dennis, Joe ; Devilee, Peter ; Dörk, Thilo ; Dos-Santos-Silva, Isabel ; Eriksson, Mikael ; Fasching, Peter A ; Figueroa, Jonine ; Flyger, Henrik ; García-Closas, Montserrat ; Giles, Graham G ; Goldberg, Mark S ; González-Neira, Anna ; Grenaker-Alnæs, Grethe ; Guénel, Pascal ; Haeberle, Lothar ; Haiman, Christopher A ; Hamann, Ute ; Hallberg, Emily ; Hooning, Maartje J ; Hopper, John L ; Jakubowska, Anna ; Jones, Michael ; Kabisch, Maria ; Kataja, Vesa ; Lambrechts, Diether ; Le Marchand, Loic ; Lindblom, Annika ; Lubinski, Jan ; Mannermaa, Arto ; Maranian, Mel ; Margolin, Sara ; Marme, Frederik ; Milne, Roger L ; Neuhausen, Susan L ; Nevanlinna, Heli ; Neven, Patrick ; Olswold, Curtis ; Peto, Julian ; Plaseska-Karanfilska, Dijana ; Pylkäs, Katri ; Radice, Paolo ; Rudolph, Anja ; Sawyer, Elinor J ; Schmidt, Marjanka K ; Shu, Xiao-Ou ; Southey, Melissa C ; Swerdlow, Anthony ; Tollenaar, Rob A E M ; Tomlinson, Ian ; Torres, Diana ; Truong, Thérèse ; Vachon, Celine ; Van Den Ouweland, Ans M W ; Wang, Qin ; Winqvist, Robert ; Zheng, Wei ; Benitez, Javier ; Chenevix-Trench, Georgia ; Dunning, Alison M ; Pharoah, Paul D P ; Kristensen, Vessela ; Hall, Per ; Easton, Douglas F ; Pastinen, Tomi ; Nord, Silje ; Simard, Jacques</creator><creatorcontrib>Hamdi, Yosr ; Soucy, Penny ; Adoue, Véronique ; Michailidou, Kyriaki ; Canisius, Sander ; Lemaçon, Audrey ; Droit, Arnaud ; Andrulis, Irene L ; Anton-Culver, Hoda ; Arndt, Volker ; Baynes, Caroline ; Blomqvist, Carl ; Bogdanova, Natalia V ; Bojesen, Stig E ; Bolla, Manjeet K ; Bonanni, Bernardo ; Borresen-Dale, Anne-Lise ; Brand, Judith S ; Brauch, Hiltrud ; Brenner, Hermann ; Broeks, Annegien ; Burwinkel, Barbara ; Chang-Claude, Jenny ; Couch, Fergus J ; Cox, Angela ; Cross, Simon S ; Czene, Kamila ; Darabi, Hatef ; Dennis, Joe ; Devilee, Peter ; Dörk, Thilo ; Dos-Santos-Silva, Isabel ; Eriksson, Mikael ; Fasching, Peter A ; Figueroa, Jonine ; Flyger, Henrik ; García-Closas, Montserrat ; Giles, Graham G ; Goldberg, Mark S ; González-Neira, Anna ; Grenaker-Alnæs, Grethe ; Guénel, Pascal ; Haeberle, Lothar ; Haiman, Christopher A ; Hamann, Ute ; Hallberg, Emily ; Hooning, Maartje J ; Hopper, John L ; Jakubowska, Anna ; Jones, Michael ; Kabisch, Maria ; Kataja, Vesa ; Lambrechts, Diether ; Le Marchand, Loic ; Lindblom, Annika ; Lubinski, Jan ; Mannermaa, Arto ; Maranian, Mel ; Margolin, Sara ; Marme, Frederik ; Milne, Roger L ; Neuhausen, Susan L ; Nevanlinna, Heli ; Neven, Patrick ; Olswold, Curtis ; Peto, Julian ; Plaseska-Karanfilska, Dijana ; Pylkäs, Katri ; Radice, Paolo ; Rudolph, Anja ; Sawyer, Elinor J ; Schmidt, Marjanka K ; Shu, Xiao-Ou ; Southey, Melissa C ; Swerdlow, Anthony ; Tollenaar, Rob A E M ; Tomlinson, Ian ; Torres, Diana ; Truong, Thérèse ; Vachon, Celine ; Van Den Ouweland, Ans M W ; Wang, Qin ; Winqvist, Robert ; Zheng, Wei ; Benitez, Javier ; Chenevix-Trench, Georgia ; Dunning, Alison M ; Pharoah, Paul D P ; Kristensen, Vessela ; Hall, Per ; Easton, Douglas F ; Pastinen, Tomi ; Nord, Silje ; Simard, Jacques ; kConFab/AOCS Investigators ; NBCS Collaborators</creatorcontrib><description>There are significant inter-individual differences in the levels of gene expression. Through modulation of gene expression, cis-acting variants represent an important source of phenotypic variation. Consequently, cis-regulatory SNPs associated with differential allelic expression are functional candidates for further investigation as disease-causing variants. To investigate whether common variants associated with differential allelic expression were involved in breast cancer susceptibility, a list of genes was established on the basis of their involvement in cancer related pathways and/or mechanisms. Thereafter, using data from a genome-wide map of allelic expression associated SNPs, 313 genetic variants were selected and their association with breast cancer risk was then evaluated in 46,451 breast cancer cases and 42,599 controls of European ancestry ascertained from 41 studies participating in the Breast Cancer Association Consortium. The associations were evaluated with overall breast cancer risk and with estrogen receptor negative and positive disease. One novel breast cancer susceptibility locus on 4q21 (rs11099601) was identified (OR = 1.05, P = 5.6x10-6). rs11099601 lies in a 135 kb linkage disequilibrium block containing several genes, including, HELQ, encoding the protein HEL308 a DNA dependant ATPase and DNA Helicase involved in DNA repair, MRPS18C encoding the Mitochondrial Ribosomal Protein S18C and FAM175A (ABRAXAS), encoding a BRCA1 BRCT domain-interacting protein involved in DNA damage response and double-strand break (DSB) repair. Expression QTL analysis in breast cancer tissue showed rs11099601 to be associated with HELQ (P = 8.28x10-14), MRPS18C (P = 1.94x10-27) and FAM175A (P = 3.83x10-3), explaining about 20%, 14% and 1%, respectively of the variance inexpression of these genes in breast carcinomas.</description><identifier>ISSN: 1949-2553</identifier><identifier>EISSN: 1949-2553</identifier><identifier>DOI: 10.18632/oncotarget.12818</identifier><identifier>PMID: 27792995</identifier><language>eng</language><publisher>United States: Impact Journals LLC</publisher><subject>Biomarkers, Tumor - genetics ; Breast Neoplasms - genetics ; Breast Neoplasms - pathology ; Canada ; Carrier Proteins - genetics ; Case-Control Studies ; Chromosomes, Human, Pair 4 ; DNA Helicases - genetics ; Europe ; Female ; Gene Frequency ; Genetic Association Studies ; Genetic Predisposition to Disease ; Humans ; Linkage Disequilibrium ; Mitochondrial Proteins - genetics ; Odds Ratio ; Phenotype ; Polymorphism, Single Nucleotide ; Priority Research Paper ; Quantitative Trait Loci ; Risk Assessment ; Risk Factors</subject><ispartof>ONCOTARGET, 2016-12, Vol.7 (49), p.80140-80163</ispartof><rights>Copyright: © 2016 Hamdi et al. 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M</creatorcontrib><creatorcontrib>Tomlinson, Ian</creatorcontrib><creatorcontrib>Torres, Diana</creatorcontrib><creatorcontrib>Truong, Thérèse</creatorcontrib><creatorcontrib>Vachon, Celine</creatorcontrib><creatorcontrib>Van Den Ouweland, Ans M W</creatorcontrib><creatorcontrib>Wang, Qin</creatorcontrib><creatorcontrib>Winqvist, Robert</creatorcontrib><creatorcontrib>Zheng, Wei</creatorcontrib><creatorcontrib>Benitez, Javier</creatorcontrib><creatorcontrib>Chenevix-Trench, Georgia</creatorcontrib><creatorcontrib>Dunning, Alison M</creatorcontrib><creatorcontrib>Pharoah, Paul D P</creatorcontrib><creatorcontrib>Kristensen, Vessela</creatorcontrib><creatorcontrib>Hall, Per</creatorcontrib><creatorcontrib>Easton, Douglas F</creatorcontrib><creatorcontrib>Pastinen, Tomi</creatorcontrib><creatorcontrib>Nord, Silje</creatorcontrib><creatorcontrib>Simard, Jacques</creatorcontrib><creatorcontrib>kConFab/AOCS Investigators</creatorcontrib><creatorcontrib>NBCS Collaborators</creatorcontrib><title>Association of breast cancer risk with genetic variants showing differential allelic expression: Identification of a novel breast cancer susceptibility locus at 4q21</title><title>ONCOTARGET</title><addtitle>Oncotarget</addtitle><description>There are significant inter-individual differences in the levels of gene expression. Through modulation of gene expression, cis-acting variants represent an important source of phenotypic variation. Consequently, cis-regulatory SNPs associated with differential allelic expression are functional candidates for further investigation as disease-causing variants. To investigate whether common variants associated with differential allelic expression were involved in breast cancer susceptibility, a list of genes was established on the basis of their involvement in cancer related pathways and/or mechanisms. Thereafter, using data from a genome-wide map of allelic expression associated SNPs, 313 genetic variants were selected and their association with breast cancer risk was then evaluated in 46,451 breast cancer cases and 42,599 controls of European ancestry ascertained from 41 studies participating in the Breast Cancer Association Consortium. The associations were evaluated with overall breast cancer risk and with estrogen receptor negative and positive disease. One novel breast cancer susceptibility locus on 4q21 (rs11099601) was identified (OR = 1.05, P = 5.6x10-6). rs11099601 lies in a 135 kb linkage disequilibrium block containing several genes, including, HELQ, encoding the protein HEL308 a DNA dependant ATPase and DNA Helicase involved in DNA repair, MRPS18C encoding the Mitochondrial Ribosomal Protein S18C and FAM175A (ABRAXAS), encoding a BRCA1 BRCT domain-interacting protein involved in DNA damage response and double-strand break (DSB) repair. Expression QTL analysis in breast cancer tissue showed rs11099601 to be associated with HELQ (P = 8.28x10-14), MRPS18C (P = 1.94x10-27) and FAM175A (P = 3.83x10-3), explaining about 20%, 14% and 1%, respectively of the variance inexpression of these genes in breast carcinomas.</description><subject>Biomarkers, Tumor - genetics</subject><subject>Breast Neoplasms - genetics</subject><subject>Breast Neoplasms - pathology</subject><subject>Canada</subject><subject>Carrier Proteins - genetics</subject><subject>Case-Control Studies</subject><subject>Chromosomes, Human, Pair 4</subject><subject>DNA Helicases - genetics</subject><subject>Europe</subject><subject>Female</subject><subject>Gene Frequency</subject><subject>Genetic Association Studies</subject><subject>Genetic Predisposition to Disease</subject><subject>Humans</subject><subject>Linkage Disequilibrium</subject><subject>Mitochondrial Proteins - genetics</subject><subject>Odds Ratio</subject><subject>Phenotype</subject><subject>Polymorphism, Single Nucleotide</subject><subject>Priority Research Paper</subject><subject>Quantitative Trait Loci</subject><subject>Risk Assessment</subject><subject>Risk 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Vessela</creator><creator>Hall, Per</creator><creator>Easton, Douglas F</creator><creator>Pastinen, Tomi</creator><creator>Nord, Silje</creator><creator>Simard, Jacques</creator><general>Impact Journals LLC</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><scope>5PM</scope><scope>ADTPV</scope><scope>AOWAS</scope><scope>D8T</scope><scope>ZZAVC</scope></search><sort><creationdate>20161206</creationdate><title>Association of breast cancer risk with genetic variants showing differential allelic expression: Identification of a novel breast cancer susceptibility locus at 4q21</title><author>Hamdi, Yosr ; Soucy, Penny ; Adoue, Véronique ; Michailidou, Kyriaki ; Canisius, Sander ; Lemaçon, Audrey ; Droit, Arnaud ; Andrulis, Irene L ; Anton-Culver, Hoda ; Arndt, Volker ; Baynes, Caroline ; Blomqvist, Carl ; Bogdanova, Natalia V ; Bojesen, Stig E ; Bolla, Manjeet K ; Bonanni, Bernardo ; Borresen-Dale, Anne-Lise ; Brand, Judith S ; Brauch, Hiltrud ; Brenner, Hermann ; Broeks, Annegien ; Burwinkel, Barbara ; Chang-Claude, Jenny ; Couch, Fergus J ; Cox, Angela ; Cross, Simon S ; Czene, Kamila ; Darabi, Hatef ; Dennis, Joe ; Devilee, Peter ; Dörk, Thilo ; Dos-Santos-Silva, Isabel ; Eriksson, Mikael ; Fasching, Peter A ; Figueroa, Jonine ; Flyger, Henrik ; García-Closas, Montserrat ; Giles, Graham G ; Goldberg, Mark S ; González-Neira, Anna ; Grenaker-Alnæs, Grethe ; Guénel, Pascal ; Haeberle, Lothar ; Haiman, Christopher A ; Hamann, Ute ; Hallberg, Emily ; Hooning, Maartje J ; Hopper, John L ; Jakubowska, Anna ; Jones, Michael ; Kabisch, Maria ; Kataja, Vesa ; Lambrechts, Diether ; Le Marchand, Loic ; Lindblom, Annika ; Lubinski, Jan ; Mannermaa, Arto ; Maranian, Mel ; Margolin, Sara ; Marme, Frederik ; Milne, Roger L ; Neuhausen, Susan L ; Nevanlinna, Heli ; Neven, Patrick ; Olswold, Curtis ; Peto, Julian ; Plaseska-Karanfilska, Dijana ; Pylkäs, Katri ; Radice, Paolo ; Rudolph, Anja ; Sawyer, Elinor J ; Schmidt, Marjanka K ; Shu, Xiao-Ou ; Southey, Melissa C ; Swerdlow, Anthony ; Tollenaar, Rob A E M ; Tomlinson, Ian ; Torres, Diana ; Truong, Thérèse ; Vachon, Celine ; Van Den Ouweland, Ans M W ; Wang, Qin ; Winqvist, Robert ; Zheng, Wei ; Benitez, Javier ; Chenevix-Trench, Georgia ; Dunning, Alison M ; Pharoah, Paul D P ; Kristensen, Vessela ; Hall, Per ; Easton, Douglas F ; Pastinen, Tomi ; Nord, Silje ; Simard, Jacques</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c437t-95b15ce0b670594f419f11c3eb6144ac8145fb4521cf6df4cc049531805f489e3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2016</creationdate><topic>Biomarkers, Tumor - genetics</topic><topic>Breast Neoplasms - genetics</topic><topic>Breast Neoplasms - pathology</topic><topic>Canada</topic><topic>Carrier Proteins - genetics</topic><topic>Case-Control Studies</topic><topic>Chromosomes, Human, Pair 4</topic><topic>DNA Helicases - genetics</topic><topic>Europe</topic><topic>Female</topic><topic>Gene Frequency</topic><topic>Genetic Association Studies</topic><topic>Genetic Predisposition to Disease</topic><topic>Humans</topic><topic>Linkage Disequilibrium</topic><topic>Mitochondrial Proteins - genetics</topic><topic>Odds Ratio</topic><topic>Phenotype</topic><topic>Polymorphism, Single Nucleotide</topic><topic>Priority Research Paper</topic><topic>Quantitative Trait Loci</topic><topic>Risk Assessment</topic><topic>Risk Factors</topic><toplevel>online_resources</toplevel><creatorcontrib>Hamdi, Yosr</creatorcontrib><creatorcontrib>Soucy, Penny</creatorcontrib><creatorcontrib>Adoue, Véronique</creatorcontrib><creatorcontrib>Michailidou, Kyriaki</creatorcontrib><creatorcontrib>Canisius, Sander</creatorcontrib><creatorcontrib>Lemaçon, Audrey</creatorcontrib><creatorcontrib>Droit, Arnaud</creatorcontrib><creatorcontrib>Andrulis, Irene L</creatorcontrib><creatorcontrib>Anton-Culver, Hoda</creatorcontrib><creatorcontrib>Arndt, Volker</creatorcontrib><creatorcontrib>Baynes, Caroline</creatorcontrib><creatorcontrib>Blomqvist, Carl</creatorcontrib><creatorcontrib>Bogdanova, Natalia V</creatorcontrib><creatorcontrib>Bojesen, Stig E</creatorcontrib><creatorcontrib>Bolla, Manjeet K</creatorcontrib><creatorcontrib>Bonanni, Bernardo</creatorcontrib><creatorcontrib>Borresen-Dale, Anne-Lise</creatorcontrib><creatorcontrib>Brand, Judith S</creatorcontrib><creatorcontrib>Brauch, Hiltrud</creatorcontrib><creatorcontrib>Brenner, Hermann</creatorcontrib><creatorcontrib>Broeks, Annegien</creatorcontrib><creatorcontrib>Burwinkel, Barbara</creatorcontrib><creatorcontrib>Chang-Claude, Jenny</creatorcontrib><creatorcontrib>Couch, Fergus J</creatorcontrib><creatorcontrib>Cox, Angela</creatorcontrib><creatorcontrib>Cross, Simon S</creatorcontrib><creatorcontrib>Czene, Kamila</creatorcontrib><creatorcontrib>Darabi, 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L</creatorcontrib><creatorcontrib>Jakubowska, Anna</creatorcontrib><creatorcontrib>Jones, Michael</creatorcontrib><creatorcontrib>Kabisch, Maria</creatorcontrib><creatorcontrib>Kataja, Vesa</creatorcontrib><creatorcontrib>Lambrechts, Diether</creatorcontrib><creatorcontrib>Le Marchand, Loic</creatorcontrib><creatorcontrib>Lindblom, Annika</creatorcontrib><creatorcontrib>Lubinski, Jan</creatorcontrib><creatorcontrib>Mannermaa, Arto</creatorcontrib><creatorcontrib>Maranian, Mel</creatorcontrib><creatorcontrib>Margolin, Sara</creatorcontrib><creatorcontrib>Marme, Frederik</creatorcontrib><creatorcontrib>Milne, Roger L</creatorcontrib><creatorcontrib>Neuhausen, Susan L</creatorcontrib><creatorcontrib>Nevanlinna, Heli</creatorcontrib><creatorcontrib>Neven, Patrick</creatorcontrib><creatorcontrib>Olswold, Curtis</creatorcontrib><creatorcontrib>Peto, Julian</creatorcontrib><creatorcontrib>Plaseska-Karanfilska, Dijana</creatorcontrib><creatorcontrib>Pylkäs, 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P</creatorcontrib><creatorcontrib>Kristensen, Vessela</creatorcontrib><creatorcontrib>Hall, Per</creatorcontrib><creatorcontrib>Easton, Douglas F</creatorcontrib><creatorcontrib>Pastinen, Tomi</creatorcontrib><creatorcontrib>Nord, Silje</creatorcontrib><creatorcontrib>Simard, Jacques</creatorcontrib><creatorcontrib>kConFab/AOCS Investigators</creatorcontrib><creatorcontrib>NBCS Collaborators</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><collection>PubMed Central (Full Participant titles)</collection><collection>SwePub</collection><collection>SwePub Articles</collection><collection>SWEPUB Freely available online</collection><collection>SwePub Articles full text</collection><jtitle>ONCOTARGET</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Hamdi, Yosr</au><au>Soucy, Penny</au><au>Adoue, Véronique</au><au>Michailidou, Kyriaki</au><au>Canisius, Sander</au><au>Lemaçon, Audrey</au><au>Droit, Arnaud</au><au>Andrulis, Irene L</au><au>Anton-Culver, Hoda</au><au>Arndt, Volker</au><au>Baynes, Caroline</au><au>Blomqvist, Carl</au><au>Bogdanova, Natalia V</au><au>Bojesen, Stig E</au><au>Bolla, Manjeet K</au><au>Bonanni, Bernardo</au><au>Borresen-Dale, Anne-Lise</au><au>Brand, Judith S</au><au>Brauch, Hiltrud</au><au>Brenner, Hermann</au><au>Broeks, Annegien</au><au>Burwinkel, Barbara</au><au>Chang-Claude, Jenny</au><au>Couch, Fergus J</au><au>Cox, Angela</au><au>Cross, Simon S</au><au>Czene, Kamila</au><au>Darabi, Hatef</au><au>Dennis, Joe</au><au>Devilee, Peter</au><au>Dörk, Thilo</au><au>Dos-Santos-Silva, Isabel</au><au>Eriksson, Mikael</au><au>Fasching, Peter A</au><au>Figueroa, Jonine</au><au>Flyger, Henrik</au><au>García-Closas, Montserrat</au><au>Giles, Graham G</au><au>Goldberg, Mark S</au><au>González-Neira, Anna</au><au>Grenaker-Alnæs, Grethe</au><au>Guénel, Pascal</au><au>Haeberle, Lothar</au><au>Haiman, Christopher A</au><au>Hamann, Ute</au><au>Hallberg, Emily</au><au>Hooning, Maartje J</au><au>Hopper, John L</au><au>Jakubowska, Anna</au><au>Jones, Michael</au><au>Kabisch, Maria</au><au>Kataja, Vesa</au><au>Lambrechts, Diether</au><au>Le Marchand, Loic</au><au>Lindblom, Annika</au><au>Lubinski, Jan</au><au>Mannermaa, Arto</au><au>Maranian, Mel</au><au>Margolin, Sara</au><au>Marme, Frederik</au><au>Milne, Roger L</au><au>Neuhausen, Susan L</au><au>Nevanlinna, Heli</au><au>Neven, Patrick</au><au>Olswold, Curtis</au><au>Peto, Julian</au><au>Plaseska-Karanfilska, Dijana</au><au>Pylkäs, Katri</au><au>Radice, Paolo</au><au>Rudolph, Anja</au><au>Sawyer, Elinor J</au><au>Schmidt, Marjanka K</au><au>Shu, Xiao-Ou</au><au>Southey, Melissa C</au><au>Swerdlow, Anthony</au><au>Tollenaar, Rob A E M</au><au>Tomlinson, Ian</au><au>Torres, Diana</au><au>Truong, Thérèse</au><au>Vachon, Celine</au><au>Van Den Ouweland, Ans M W</au><au>Wang, Qin</au><au>Winqvist, Robert</au><au>Zheng, Wei</au><au>Benitez, Javier</au><au>Chenevix-Trench, Georgia</au><au>Dunning, Alison M</au><au>Pharoah, Paul D P</au><au>Kristensen, Vessela</au><au>Hall, Per</au><au>Easton, Douglas F</au><au>Pastinen, Tomi</au><au>Nord, Silje</au><au>Simard, Jacques</au><aucorp>kConFab/AOCS Investigators</aucorp><aucorp>NBCS Collaborators</aucorp><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Association of breast cancer risk with genetic variants showing differential allelic expression: Identification of a novel breast cancer susceptibility locus at 4q21</atitle><jtitle>ONCOTARGET</jtitle><addtitle>Oncotarget</addtitle><date>2016-12-06</date><risdate>2016</risdate><volume>7</volume><issue>49</issue><spage>80140</spage><epage>80163</epage><pages>80140-80163</pages><issn>1949-2553</issn><eissn>1949-2553</eissn><abstract>There are significant inter-individual differences in the levels of gene expression. Through modulation of gene expression, cis-acting variants represent an important source of phenotypic variation. Consequently, cis-regulatory SNPs associated with differential allelic expression are functional candidates for further investigation as disease-causing variants. To investigate whether common variants associated with differential allelic expression were involved in breast cancer susceptibility, a list of genes was established on the basis of their involvement in cancer related pathways and/or mechanisms. Thereafter, using data from a genome-wide map of allelic expression associated SNPs, 313 genetic variants were selected and their association with breast cancer risk was then evaluated in 46,451 breast cancer cases and 42,599 controls of European ancestry ascertained from 41 studies participating in the Breast Cancer Association Consortium. The associations were evaluated with overall breast cancer risk and with estrogen receptor negative and positive disease. One novel breast cancer susceptibility locus on 4q21 (rs11099601) was identified (OR = 1.05, P = 5.6x10-6). rs11099601 lies in a 135 kb linkage disequilibrium block containing several genes, including, HELQ, encoding the protein HEL308 a DNA dependant ATPase and DNA Helicase involved in DNA repair, MRPS18C encoding the Mitochondrial Ribosomal Protein S18C and FAM175A (ABRAXAS), encoding a BRCA1 BRCT domain-interacting protein involved in DNA damage response and double-strand break (DSB) repair. Expression QTL analysis in breast cancer tissue showed rs11099601 to be associated with HELQ (P = 8.28x10-14), MRPS18C (P = 1.94x10-27) and FAM175A (P = 3.83x10-3), explaining about 20%, 14% and 1%, respectively of the variance inexpression of these genes in breast carcinomas.</abstract><cop>United States</cop><pub>Impact Journals LLC</pub><pmid>27792995</pmid><doi>10.18632/oncotarget.12818</doi><tpages>24</tpages><oa>free_for_read</oa></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 1949-2553 |
| ispartof | ONCOTARGET, 2016-12, Vol.7 (49), p.80140-80163 |
| issn | 1949-2553 1949-2553 |
| language | eng |
| recordid | cdi_swepub_primary_oai_swepub_ki_se_501440 |
| source | MEDLINE; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals; SWEPUB Freely available online; PubMed Central Open Access; PubMed Central; Free E- Journals |
| subjects | Biomarkers, Tumor - genetics Breast Neoplasms - genetics Breast Neoplasms - pathology Canada Carrier Proteins - genetics Case-Control Studies Chromosomes, Human, Pair 4 DNA Helicases - genetics Europe Female Gene Frequency Genetic Association Studies Genetic Predisposition to Disease Humans Linkage Disequilibrium Mitochondrial Proteins - genetics Odds Ratio Phenotype Polymorphism, Single Nucleotide Priority Research Paper Quantitative Trait Loci Risk Assessment Risk Factors |
| title | Association of breast cancer risk with genetic variants showing differential allelic expression: Identification of a novel breast cancer susceptibility locus at 4q21 |
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