Fine mapping of chromosome 5p15.33 based on a targeted deep sequencing and high density genotyping identifies novel lung cancer susceptibility loci
Chromosome 5p15.33 has been identified as a lung cancer susceptibility locus, however the underlying causal mechanisms were not fully elucidated. Previous fine-mapping studies of this locus have relied on imputation or investigated a small number of known, common variants. This study represents a si...
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| Veröffentlicht in: | Carcinogenesis (New York) 2016-01, Vol.37 (1), p.96-105 |
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| creator | Kachuri, Linda Amos, Christopher I McKay, James D Johansson, Mattias Vineis, Paolo Bueno-de-Mesquita, H Bas Boutron-Ruault, Marie-Christine Johansson, Mikael Quirós, J Ramón Sieri, Sabina Travis, Ruth C Weiderpass, Elisabete Le Marchand, Loic Henderson, Brian E Wilkens, Lynne Goodman, Gary E Chen, Chu Doherty, Jennifer A Christiani, David C Wei, Yongyue Su, Li Tworoger, Shelley Zhang, Xuehong Kraft, Peter Zaridze, David Field, John K Marcus, Michael W Davies, Michael P A Hyde, Russell Caporaso, Neil E Landi, Maria Teresa Severi, Gianluca Giles, Graham G Liu, Geoffrey McLaughlin, John R Li, Yafang Xiao, Xiangjun Fehringer, Gord Zong, Xuchen Denroche, Robert E Zuzarte, Philip C McPherson, John D Brennan, Paul Hung, Rayjean J |
| description | Chromosome 5p15.33 has been identified as a lung cancer susceptibility locus, however the underlying causal mechanisms were not fully elucidated. Previous fine-mapping studies of this locus have relied on imputation or investigated a small number of known, common variants. This study represents a significant advance over previous research by investigating a large number of novel, rare variants, as well as their underlying mechanisms through telomere length. Variants for this fine-mapping study were identified through a targeted deep sequencing (average depth of coverage greater than 4000×) of 576 individuals. Subsequently, 4652 SNPs, including 1108 novel SNPs, were genotyped in 5164 cases and 5716 controls of European ancestry. After adjusting for known risk loci, rs2736100 and rs401681, we identified a new, independent lung cancer susceptibility variant in LPCAT1: rs139852726 (OR = 0.46, P = 4.73×10(-9)), and three new adenocarcinoma risk variants in TERT: rs61748181 (OR = 0.53, P = 2.64×10(-6)), rs112290073 (OR = 1.85, P = 1.27×10(-5)), rs138895564 (OR = 2.16, P = 2.06×10(-5); among young cases, OR = 3.77, P = 8.41×10(-4)). In addition, we found that rs139852726 (P = 1.44×10(-3)) was associated with telomere length in a sample of 922 healthy individuals. The gene-based SKAT-O analysis implicated TERT as the most relevant gene in the 5p15.33 region for adenocarcinoma (P = 7.84×10(-7)) and lung cancer (P = 2.37×10(-5)) risk. In this largest fine-mapping study to investigate a large number of rare and novel variants within 5p15.33, we identified novel lung and adenocarcinoma susceptibility loci with large effects and provided support for the role of telomere length as the potential underlying mechanism. |
| doi_str_mv | 10.1093/carcin/bgv165 |
| format | Article |
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Previous fine-mapping studies of this locus have relied on imputation or investigated a small number of known, common variants. This study represents a significant advance over previous research by investigating a large number of novel, rare variants, as well as their underlying mechanisms through telomere length. Variants for this fine-mapping study were identified through a targeted deep sequencing (average depth of coverage greater than 4000×) of 576 individuals. Subsequently, 4652 SNPs, including 1108 novel SNPs, were genotyped in 5164 cases and 5716 controls of European ancestry. After adjusting for known risk loci, rs2736100 and rs401681, we identified a new, independent lung cancer susceptibility variant in LPCAT1: rs139852726 (OR = 0.46, P = 4.73×10(-9)), and three new adenocarcinoma risk variants in TERT: rs61748181 (OR = 0.53, P = 2.64×10(-6)), rs112290073 (OR = 1.85, P = 1.27×10(-5)), rs138895564 (OR = 2.16, P = 2.06×10(-5); among young cases, OR = 3.77, P = 8.41×10(-4)). In addition, we found that rs139852726 (P = 1.44×10(-3)) was associated with telomere length in a sample of 922 healthy individuals. The gene-based SKAT-O analysis implicated TERT as the most relevant gene in the 5p15.33 region for adenocarcinoma (P = 7.84×10(-7)) and lung cancer (P = 2.37×10(-5)) risk. In this largest fine-mapping study to investigate a large number of rare and novel variants within 5p15.33, we identified novel lung and adenocarcinoma susceptibility loci with large effects and provided support for the role of telomere length as the potential underlying mechanism.</description><identifier>ISSN: 0143-3334</identifier><identifier>ISSN: 1460-2180</identifier><identifier>EISSN: 1460-2180</identifier><identifier>DOI: 10.1093/carcin/bgv165</identifier><identifier>PMID: 26590902</identifier><language>eng</language><publisher>England: Oxford University Press</publisher><subject>Case-Control Studies ; Chromosome Mapping - methods ; Chromosomes, Human, Pair 5 ; Female ; Genetic Loci ; Genetic Predisposition to Disease ; Genotyping Techniques - methods ; Humans ; Lung Neoplasms - genetics ; Male ; Middle Aged ; Original Manuscript</subject><ispartof>Carcinogenesis (New York), 2016-01, Vol.37 (1), p.96-105</ispartof><rights>The Author 2015. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.</rights><rights>The Author 2015. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com. 2015</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c529t-49dadd979333127718501868013da2ef8ebb5dab1c60b633fc2e9082f03296183</citedby><cites>FETCH-LOGICAL-c529t-49dadd979333127718501868013da2ef8ebb5dab1c60b633fc2e9082f03296183</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>230,314,550,776,780,881,27901,27902</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/26590902$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink><backlink>$$Uhttps://urn.kb.se/resolve?urn=urn:nbn:se:umu:diva-116749$$DView record from Swedish Publication Index$$Hfree_for_read</backlink><backlink>$$Uhttp://kipublications.ki.se/Default.aspx?queryparsed=id:132807806$$DView record from Swedish Publication Index$$Hfree_for_read</backlink></links><search><creatorcontrib>Kachuri, Linda</creatorcontrib><creatorcontrib>Amos, Christopher I</creatorcontrib><creatorcontrib>McKay, James D</creatorcontrib><creatorcontrib>Johansson, Mattias</creatorcontrib><creatorcontrib>Vineis, Paolo</creatorcontrib><creatorcontrib>Bueno-de-Mesquita, H Bas</creatorcontrib><creatorcontrib>Boutron-Ruault, Marie-Christine</creatorcontrib><creatorcontrib>Johansson, Mikael</creatorcontrib><creatorcontrib>Quirós, J Ramón</creatorcontrib><creatorcontrib>Sieri, Sabina</creatorcontrib><creatorcontrib>Travis, Ruth C</creatorcontrib><creatorcontrib>Weiderpass, Elisabete</creatorcontrib><creatorcontrib>Le Marchand, Loic</creatorcontrib><creatorcontrib>Henderson, Brian E</creatorcontrib><creatorcontrib>Wilkens, Lynne</creatorcontrib><creatorcontrib>Goodman, Gary E</creatorcontrib><creatorcontrib>Chen, Chu</creatorcontrib><creatorcontrib>Doherty, Jennifer A</creatorcontrib><creatorcontrib>Christiani, David C</creatorcontrib><creatorcontrib>Wei, Yongyue</creatorcontrib><creatorcontrib>Su, Li</creatorcontrib><creatorcontrib>Tworoger, Shelley</creatorcontrib><creatorcontrib>Zhang, Xuehong</creatorcontrib><creatorcontrib>Kraft, Peter</creatorcontrib><creatorcontrib>Zaridze, David</creatorcontrib><creatorcontrib>Field, John K</creatorcontrib><creatorcontrib>Marcus, Michael W</creatorcontrib><creatorcontrib>Davies, Michael P A</creatorcontrib><creatorcontrib>Hyde, Russell</creatorcontrib><creatorcontrib>Caporaso, Neil E</creatorcontrib><creatorcontrib>Landi, Maria Teresa</creatorcontrib><creatorcontrib>Severi, Gianluca</creatorcontrib><creatorcontrib>Giles, Graham G</creatorcontrib><creatorcontrib>Liu, Geoffrey</creatorcontrib><creatorcontrib>McLaughlin, John R</creatorcontrib><creatorcontrib>Li, Yafang</creatorcontrib><creatorcontrib>Xiao, Xiangjun</creatorcontrib><creatorcontrib>Fehringer, Gord</creatorcontrib><creatorcontrib>Zong, Xuchen</creatorcontrib><creatorcontrib>Denroche, Robert E</creatorcontrib><creatorcontrib>Zuzarte, Philip C</creatorcontrib><creatorcontrib>McPherson, John D</creatorcontrib><creatorcontrib>Brennan, Paul</creatorcontrib><creatorcontrib>Hung, Rayjean J</creatorcontrib><title>Fine mapping of chromosome 5p15.33 based on a targeted deep sequencing and high density genotyping identifies novel lung cancer susceptibility loci</title><title>Carcinogenesis (New York)</title><addtitle>Carcinogenesis</addtitle><description>Chromosome 5p15.33 has been identified as a lung cancer susceptibility locus, however the underlying causal mechanisms were not fully elucidated. Previous fine-mapping studies of this locus have relied on imputation or investigated a small number of known, common variants. This study represents a significant advance over previous research by investigating a large number of novel, rare variants, as well as their underlying mechanisms through telomere length. Variants for this fine-mapping study were identified through a targeted deep sequencing (average depth of coverage greater than 4000×) of 576 individuals. Subsequently, 4652 SNPs, including 1108 novel SNPs, were genotyped in 5164 cases and 5716 controls of European ancestry. After adjusting for known risk loci, rs2736100 and rs401681, we identified a new, independent lung cancer susceptibility variant in LPCAT1: rs139852726 (OR = 0.46, P = 4.73×10(-9)), and three new adenocarcinoma risk variants in TERT: rs61748181 (OR = 0.53, P = 2.64×10(-6)), rs112290073 (OR = 1.85, P = 1.27×10(-5)), rs138895564 (OR = 2.16, P = 2.06×10(-5); among young cases, OR = 3.77, P = 8.41×10(-4)). In addition, we found that rs139852726 (P = 1.44×10(-3)) was associated with telomere length in a sample of 922 healthy individuals. The gene-based SKAT-O analysis implicated TERT as the most relevant gene in the 5p15.33 region for adenocarcinoma (P = 7.84×10(-7)) and lung cancer (P = 2.37×10(-5)) risk. In this largest fine-mapping study to investigate a large number of rare and novel variants within 5p15.33, we identified novel lung and adenocarcinoma susceptibility loci with large effects and provided support for the role of telomere length as the potential underlying mechanism.</description><subject>Case-Control Studies</subject><subject>Chromosome Mapping - methods</subject><subject>Chromosomes, Human, Pair 5</subject><subject>Female</subject><subject>Genetic Loci</subject><subject>Genetic Predisposition to Disease</subject><subject>Genotyping Techniques - methods</subject><subject>Humans</subject><subject>Lung Neoplasms - genetics</subject><subject>Male</subject><subject>Middle Aged</subject><subject>Original Manuscript</subject><issn>0143-3334</issn><issn>1460-2180</issn><issn>1460-2180</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2016</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>D8T</sourceid><recordid>eNp9kcFu1DAQhi0EokvhyBX5BdJ67NgbX5CqQgGpEhfgajnOJGtI7GAni_Y5eGG8bCn0wsn2P98_o_FPyEtgF8C0uHQ2OR8u22EPSj4iG6gVqzg07DHZMKhFJYSoz8iznL8yBkpI_ZSccSU104xvyM8bH5BOdp59GGjsqdulOMUcJ6RyBnkhBG1txo7GQC1dbBpwKa8OcaYZv68Y3NFpQ0d3ftiVQsh-OdABQ1wOv7v6oi2-95hpiHsc6bgW1dngMNG8Zofz4ls_Hm1jdP45edLbMeOLu_OcfL55--n6fXX78d2H66vbykmul6rWne06vdVlQ-DbLTSSQaMaBqKzHPsG21Z2tgWnWKuE6B1HzRreM8G1gkack-rUN__AeW3NnPxk08FE682d9K3c0EimQcr_8m_8lysT02DWaTUAalvrwr8-8QWesHPlF5IdH9geVoLfmSHuTb0FyYX6O9ClmHPC_t4LzBzTN6f0zSn9wr_6d-A9_Sdu8QuBjbF5</recordid><startdate>20160101</startdate><enddate>20160101</enddate><creator>Kachuri, Linda</creator><creator>Amos, Christopher I</creator><creator>McKay, James D</creator><creator>Johansson, Mattias</creator><creator>Vineis, Paolo</creator><creator>Bueno-de-Mesquita, H Bas</creator><creator>Boutron-Ruault, Marie-Christine</creator><creator>Johansson, Mikael</creator><creator>Quirós, J Ramón</creator><creator>Sieri, Sabina</creator><creator>Travis, Ruth C</creator><creator>Weiderpass, Elisabete</creator><creator>Le Marchand, Loic</creator><creator>Henderson, Brian E</creator><creator>Wilkens, Lynne</creator><creator>Goodman, Gary E</creator><creator>Chen, Chu</creator><creator>Doherty, Jennifer A</creator><creator>Christiani, David C</creator><creator>Wei, Yongyue</creator><creator>Su, Li</creator><creator>Tworoger, Shelley</creator><creator>Zhang, Xuehong</creator><creator>Kraft, Peter</creator><creator>Zaridze, David</creator><creator>Field, John K</creator><creator>Marcus, Michael W</creator><creator>Davies, Michael P A</creator><creator>Hyde, Russell</creator><creator>Caporaso, Neil E</creator><creator>Landi, Maria Teresa</creator><creator>Severi, Gianluca</creator><creator>Giles, Graham G</creator><creator>Liu, Geoffrey</creator><creator>McLaughlin, John R</creator><creator>Li, Yafang</creator><creator>Xiao, Xiangjun</creator><creator>Fehringer, Gord</creator><creator>Zong, Xuchen</creator><creator>Denroche, Robert E</creator><creator>Zuzarte, Philip C</creator><creator>McPherson, John D</creator><creator>Brennan, Paul</creator><creator>Hung, Rayjean J</creator><general>Oxford University Press</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>5PM</scope><scope>ADTPV</scope><scope>AOWAS</scope><scope>D93</scope><scope>D8T</scope><scope>ZZAVC</scope></search><sort><creationdate>20160101</creationdate><title>Fine mapping of chromosome 5p15.33 based on a targeted deep sequencing and high density genotyping identifies novel lung cancer susceptibility loci</title><author>Kachuri, Linda ; Amos, Christopher I ; McKay, James D ; Johansson, Mattias ; Vineis, Paolo ; Bueno-de-Mesquita, H Bas ; Boutron-Ruault, Marie-Christine ; Johansson, Mikael ; Quirós, J Ramón ; Sieri, Sabina ; Travis, Ruth C ; Weiderpass, Elisabete ; Le Marchand, Loic ; Henderson, Brian E ; Wilkens, Lynne ; Goodman, Gary E ; Chen, Chu ; Doherty, Jennifer A ; Christiani, David C ; Wei, Yongyue ; Su, Li ; Tworoger, Shelley ; Zhang, Xuehong ; Kraft, Peter ; Zaridze, David ; Field, John K ; Marcus, Michael W ; Davies, Michael P A ; Hyde, Russell ; Caporaso, Neil E ; Landi, Maria Teresa ; Severi, Gianluca ; Giles, Graham G ; Liu, Geoffrey ; McLaughlin, John R ; Li, Yafang ; Xiao, Xiangjun ; Fehringer, Gord ; Zong, Xuchen ; Denroche, Robert E ; Zuzarte, Philip C ; McPherson, John D ; Brennan, Paul ; Hung, Rayjean J</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c529t-49dadd979333127718501868013da2ef8ebb5dab1c60b633fc2e9082f03296183</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2016</creationdate><topic>Case-Control Studies</topic><topic>Chromosome Mapping - methods</topic><topic>Chromosomes, Human, Pair 5</topic><topic>Female</topic><topic>Genetic Loci</topic><topic>Genetic Predisposition to Disease</topic><topic>Genotyping Techniques - methods</topic><topic>Humans</topic><topic>Lung Neoplasms - genetics</topic><topic>Male</topic><topic>Middle Aged</topic><topic>Original Manuscript</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Kachuri, Linda</creatorcontrib><creatorcontrib>Amos, Christopher I</creatorcontrib><creatorcontrib>McKay, James D</creatorcontrib><creatorcontrib>Johansson, Mattias</creatorcontrib><creatorcontrib>Vineis, Paolo</creatorcontrib><creatorcontrib>Bueno-de-Mesquita, H Bas</creatorcontrib><creatorcontrib>Boutron-Ruault, Marie-Christine</creatorcontrib><creatorcontrib>Johansson, Mikael</creatorcontrib><creatorcontrib>Quirós, J Ramón</creatorcontrib><creatorcontrib>Sieri, Sabina</creatorcontrib><creatorcontrib>Travis, Ruth C</creatorcontrib><creatorcontrib>Weiderpass, Elisabete</creatorcontrib><creatorcontrib>Le Marchand, Loic</creatorcontrib><creatorcontrib>Henderson, Brian E</creatorcontrib><creatorcontrib>Wilkens, Lynne</creatorcontrib><creatorcontrib>Goodman, Gary E</creatorcontrib><creatorcontrib>Chen, Chu</creatorcontrib><creatorcontrib>Doherty, Jennifer A</creatorcontrib><creatorcontrib>Christiani, David C</creatorcontrib><creatorcontrib>Wei, Yongyue</creatorcontrib><creatorcontrib>Su, Li</creatorcontrib><creatorcontrib>Tworoger, Shelley</creatorcontrib><creatorcontrib>Zhang, Xuehong</creatorcontrib><creatorcontrib>Kraft, Peter</creatorcontrib><creatorcontrib>Zaridze, David</creatorcontrib><creatorcontrib>Field, John K</creatorcontrib><creatorcontrib>Marcus, Michael W</creatorcontrib><creatorcontrib>Davies, Michael P A</creatorcontrib><creatorcontrib>Hyde, Russell</creatorcontrib><creatorcontrib>Caporaso, Neil E</creatorcontrib><creatorcontrib>Landi, Maria Teresa</creatorcontrib><creatorcontrib>Severi, Gianluca</creatorcontrib><creatorcontrib>Giles, Graham G</creatorcontrib><creatorcontrib>Liu, Geoffrey</creatorcontrib><creatorcontrib>McLaughlin, John R</creatorcontrib><creatorcontrib>Li, Yafang</creatorcontrib><creatorcontrib>Xiao, Xiangjun</creatorcontrib><creatorcontrib>Fehringer, Gord</creatorcontrib><creatorcontrib>Zong, Xuchen</creatorcontrib><creatorcontrib>Denroche, Robert E</creatorcontrib><creatorcontrib>Zuzarte, Philip C</creatorcontrib><creatorcontrib>McPherson, John D</creatorcontrib><creatorcontrib>Brennan, Paul</creatorcontrib><creatorcontrib>Hung, Rayjean J</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>PubMed Central (Full Participant titles)</collection><collection>SwePub</collection><collection>SwePub Articles</collection><collection>SWEPUB Umeå universitet</collection><collection>SWEPUB Freely available online</collection><collection>SwePub Articles full text</collection><jtitle>Carcinogenesis (New York)</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Kachuri, Linda</au><au>Amos, Christopher I</au><au>McKay, James D</au><au>Johansson, Mattias</au><au>Vineis, Paolo</au><au>Bueno-de-Mesquita, H Bas</au><au>Boutron-Ruault, Marie-Christine</au><au>Johansson, Mikael</au><au>Quirós, J Ramón</au><au>Sieri, Sabina</au><au>Travis, Ruth C</au><au>Weiderpass, Elisabete</au><au>Le Marchand, Loic</au><au>Henderson, Brian E</au><au>Wilkens, Lynne</au><au>Goodman, Gary E</au><au>Chen, Chu</au><au>Doherty, Jennifer A</au><au>Christiani, David C</au><au>Wei, Yongyue</au><au>Su, Li</au><au>Tworoger, Shelley</au><au>Zhang, Xuehong</au><au>Kraft, Peter</au><au>Zaridze, David</au><au>Field, John K</au><au>Marcus, Michael W</au><au>Davies, Michael P A</au><au>Hyde, Russell</au><au>Caporaso, Neil E</au><au>Landi, Maria Teresa</au><au>Severi, Gianluca</au><au>Giles, Graham G</au><au>Liu, Geoffrey</au><au>McLaughlin, John R</au><au>Li, Yafang</au><au>Xiao, Xiangjun</au><au>Fehringer, Gord</au><au>Zong, Xuchen</au><au>Denroche, Robert E</au><au>Zuzarte, Philip C</au><au>McPherson, John D</au><au>Brennan, Paul</au><au>Hung, Rayjean J</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Fine mapping of chromosome 5p15.33 based on a targeted deep sequencing and high density genotyping identifies novel lung cancer susceptibility loci</atitle><jtitle>Carcinogenesis (New York)</jtitle><addtitle>Carcinogenesis</addtitle><date>2016-01-01</date><risdate>2016</risdate><volume>37</volume><issue>1</issue><spage>96</spage><epage>105</epage><pages>96-105</pages><issn>0143-3334</issn><issn>1460-2180</issn><eissn>1460-2180</eissn><abstract>Chromosome 5p15.33 has been identified as a lung cancer susceptibility locus, however the underlying causal mechanisms were not fully elucidated. Previous fine-mapping studies of this locus have relied on imputation or investigated a small number of known, common variants. This study represents a significant advance over previous research by investigating a large number of novel, rare variants, as well as their underlying mechanisms through telomere length. Variants for this fine-mapping study were identified through a targeted deep sequencing (average depth of coverage greater than 4000×) of 576 individuals. Subsequently, 4652 SNPs, including 1108 novel SNPs, were genotyped in 5164 cases and 5716 controls of European ancestry. After adjusting for known risk loci, rs2736100 and rs401681, we identified a new, independent lung cancer susceptibility variant in LPCAT1: rs139852726 (OR = 0.46, P = 4.73×10(-9)), and three new adenocarcinoma risk variants in TERT: rs61748181 (OR = 0.53, P = 2.64×10(-6)), rs112290073 (OR = 1.85, P = 1.27×10(-5)), rs138895564 (OR = 2.16, P = 2.06×10(-5); among young cases, OR = 3.77, P = 8.41×10(-4)). In addition, we found that rs139852726 (P = 1.44×10(-3)) was associated with telomere length in a sample of 922 healthy individuals. The gene-based SKAT-O analysis implicated TERT as the most relevant gene in the 5p15.33 region for adenocarcinoma (P = 7.84×10(-7)) and lung cancer (P = 2.37×10(-5)) risk. In this largest fine-mapping study to investigate a large number of rare and novel variants within 5p15.33, we identified novel lung and adenocarcinoma susceptibility loci with large effects and provided support for the role of telomere length as the potential underlying mechanism.</abstract><cop>England</cop><pub>Oxford University Press</pub><pmid>26590902</pmid><doi>10.1093/carcin/bgv165</doi><tpages>10</tpages><oa>free_for_read</oa></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 0143-3334 |
| ispartof | Carcinogenesis (New York), 2016-01, Vol.37 (1), p.96-105 |
| issn | 0143-3334 1460-2180 1460-2180 |
| language | eng |
| recordid | cdi_swepub_primary_oai_swepub_ki_se_509155 |
| source | Oxford University Press Journals All Titles (1996-Current); MEDLINE; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals; Alma/SFX Local Collection; SWEPUB Freely available online |
| subjects | Case-Control Studies Chromosome Mapping - methods Chromosomes, Human, Pair 5 Female Genetic Loci Genetic Predisposition to Disease Genotyping Techniques - methods Humans Lung Neoplasms - genetics Male Middle Aged Original Manuscript |
| title | Fine mapping of chromosome 5p15.33 based on a targeted deep sequencing and high density genotyping identifies novel lung cancer susceptibility loci |
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