A Genome-wide Association Study of Lung Cancer Identifies a Region of Chromosome 5p15 Associated with Risk for Adenocarcinoma

Maria Teresa Landi; Nilanjan Chatterjee; Kai Yu; Lynn R. Goldin; Alisa M. Goldstein; Melissa Rotunno; Lisa Mirabello; Kevin Jacobs; William Wheeler; Meredith Yeager; Andrew W. Bergen; Qizhai Li; Dario Consonni; Angela C. Pesatori; Sholom Wacholder; Michael Thun; Ryan Diver; Martin Oken; Jarmo Virtamo; Demetrius Albanes; Zhaoming Wang; Laurie Burdette; Kimberly F. Doheny; Elizabeth W. Pugh; Cathy Laurie; Paul Brennan; Rayjean Hung; Valerie Gaborieau; James D. McKay; Mark Lathrop; John McLaughlin; Ying Wang; Ming Sound Tsao; Margaret R. Spitz; Yufei Wang; Hans Krokan; Lars Vatten; Frank Skorpen; Egil Arnesen; Simone Benhamou; Christine Bouchard; Andres Metsapalu; Tonu Vooder; Mari Nelis; Kristian Välk; John K. Field; Chu Chen; Gary Goodman; Patrick Sulem; Gudmar Thorleifsson; Thorunn Rafnar; Timothy Eisen; Wiebke Sauter; Albert Rosenberger; Heike Bickeböller; Angela Risch; Jenny Chang-Claude; H. Erich Wichmann; Kari Stefansson; Richard Houlston; Christopher I. Amos; Joseph F. Fraumeni; Sharon A. Savage; Pier Alberto Bertazzi; Margaret A. Tucker; Stephen Chanock; Neil E. Caporaso

doi:10.1016/j.ajhg.2009.09.012

A Genome-wide Association Study of Lung Cancer Identifies a Region of Chromosome 5p15 Associated with Risk for Adenocarcinoma

Maria Teresa Landi, Nilanjan Chatterjee, Kai Yu, Lynn R. Goldin, Alisa M. Goldstein, Melissa Rotunno, Lisa Mirabello, Kevin Jacobs, William Wheeler, Meredith Yeager, Andrew W. Bergen, Qizhai Li, Dario Consonni, Angela C. Pesatori, Sholom Wacholder, Michael Thun, Ryan Diver, Martin Oken, Jarmo Virtamo, Demetrius AlbanesZhaoming Wang, Laurie Burdette, Kimberly F. Doheny, Elizabeth W. Pugh, Cathy Laurie, Paul Brennan, Rayjean Hung, Valerie Gaborieau, James D. McKay, Mark Lathrop, John McLaughlin, Ying Wang, Ming Sound Tsao, Margaret R. Spitz, Yufei Wang, Hans Krokan, Lars Vatten, Frank Skorpen, Egil Arnesen, Simone Benhamou, Christine Bouchard, Andres Metsapalu, Tonu Vooder, Mari Nelis, Kristian Välk, John K. Field, Chu Chen, Gary Goodman, Patrick Sulem, Gudmar Thorleifsson, Thorunn Rafnar, Timothy Eisen, Wiebke Sauter, Albert Rosenberger, Heike Bickeböller, Angela Risch, Jenny Chang-Claude, H. Erich Wichmann, Kari Stefansson, Richard Houlston, Christopher I. Amos, Joseph F. Fraumeni, Sharon A. Savage, Pier Alberto Bertazzi, Margaret A. Tucker, Stephen Chanock, Neil E. Caporaso

School of Medicine

Research output: Contribution to journal › Article › peer-review

420 Scopus citations

Abstract

Three genetic loci for lung cancer risk have been identified by genome-wide association studies (GWAS), but inherited susceptibility to specific histologic types of lung cancer is not well established. We conducted a GWAS of lung cancer and its major histologic types, genotyping 515,922 single-nucleotide polymorphisms (SNPs) in 5739 lung cancer cases and 5848 controls from one population-based case-control study and three cohort studies. Results were combined with summary data from ten additional studies, for a total of 13,300 cases and 19,666 controls of European descent. Four studies also provided histology data for replication, resulting in 3333 adenocarcinomas (AD), 2589 squamous cell carcinomas (SQ), and 1418 small cell carcinomas (SC). In analyses by histology, rs2736100 (TERT), on chromosome 5p15.33, was associated with risk of adenocarcinoma (odds ratio [OR] = 1.23, 95% confidence interval [CI] = 1.13-1.33, p = 3.02 × 10^-7), but not with other histologic types (OR = 1.01, p = 0.84 and OR = 1.00, p = 0.93 for SQ and SC, respectively). This finding was confirmed in each replication study and overall meta-analysis (OR = 1.24, 95% CI = 1.17-1.31, p = 3.74 × 10^-14 for AD; OR = 0.99, p = 0.69 and OR = 0.97, p = 0.48 for SQ and SC, respectively). Other previously reported association signals on 15q25 and 6p21 were also refined, but no additional loci reached genome-wide significance. In conclusion, a lung cancer GWAS identified a distinct hereditary contribution to adenocarcinoma.

Original language	English (US)
Pages (from-to)	679-691
Number of pages	13
Journal	American journal of human genetics
Volume	85
Issue number	5
DOIs	https://doi.org/10.1016/j.ajhg.2009.09.012
State	Published - Nov 13 2009

ASJC Scopus subject areas

Genetics
Genetics(clinical)

Access to Document

10.1016/j.ajhg.2009.09.012

Cite this

Landi, M. T., Chatterjee, N., Yu, K., Goldin, L. R., Goldstein, A. M., Rotunno, M., Mirabello, L., Jacobs, K., Wheeler, W., Yeager, M., Bergen, A. W., Li, Q., Consonni, D., Pesatori, A. C., Wacholder, S., Thun, M., Diver, R., Oken, M., Virtamo, J., ... Caporaso, N. E. (2009). A Genome-wide Association Study of Lung Cancer Identifies a Region of Chromosome 5p15 Associated with Risk for Adenocarcinoma. American journal of human genetics, 85(5), 679-691. https://doi.org/10.1016/j.ajhg.2009.09.012

Landi, MT, Chatterjee, N, Yu, K, Goldin, LR, Goldstein, AM, Rotunno, M, Mirabello, L, Jacobs, K, Wheeler, W, Yeager, M, Bergen, AW, Li, Q, Consonni, D, Pesatori, AC, Wacholder, S, Thun, M, Diver, R, Oken, M, Virtamo, J, Albanes, D, Wang, Z, Burdette, L, Doheny, KF, Pugh, EW, Laurie, C, Brennan, P, Hung, R, Gaborieau, V, McKay, JD, Lathrop, M, McLaughlin, J, Wang, Y, Tsao, MS, Spitz, MR, Wang, Y, Krokan, H, Vatten, L, Skorpen, F, Arnesen, E, Benhamou, S, Bouchard, C, Metsapalu, A, Vooder, T, Nelis, M, Välk, K, Field, JK, Chen, C, Goodman, G, Sulem, P, Thorleifsson, G, Rafnar, T, Eisen, T, Sauter, W, Rosenberger, A, Bickeböller, H, Risch, A, Chang-Claude, J, Wichmann, HE, Stefansson, K, Houlston, R, Amos, CI, Fraumeni, JF, Savage, SA, Bertazzi, PA, Tucker, MA, Chanock, S & Caporaso, NE 2009, 'A Genome-wide Association Study of Lung Cancer Identifies a Region of Chromosome 5p15 Associated with Risk for Adenocarcinoma', American journal of human genetics, vol. 85, no. 5, pp. 679-691. https://doi.org/10.1016/j.ajhg.2009.09.012

@article{5c0b0a6ff3a1417a9b24f125b4e0608e,

title = "A Genome-wide Association Study of Lung Cancer Identifies a Region of Chromosome 5p15 Associated with Risk for Adenocarcinoma",

abstract = "Three genetic loci for lung cancer risk have been identified by genome-wide association studies (GWAS), but inherited susceptibility to specific histologic types of lung cancer is not well established. We conducted a GWAS of lung cancer and its major histologic types, genotyping 515,922 single-nucleotide polymorphisms (SNPs) in 5739 lung cancer cases and 5848 controls from one population-based case-control study and three cohort studies. Results were combined with summary data from ten additional studies, for a total of 13,300 cases and 19,666 controls of European descent. Four studies also provided histology data for replication, resulting in 3333 adenocarcinomas (AD), 2589 squamous cell carcinomas (SQ), and 1418 small cell carcinomas (SC). In analyses by histology, rs2736100 (TERT), on chromosome 5p15.33, was associated with risk of adenocarcinoma (odds ratio [OR] = 1.23, 95% confidence interval [CI] = 1.13-1.33, p = 3.02 × 10-7), but not with other histologic types (OR = 1.01, p = 0.84 and OR = 1.00, p = 0.93 for SQ and SC, respectively). This finding was confirmed in each replication study and overall meta-analysis (OR = 1.24, 95% CI = 1.17-1.31, p = 3.74 × 10-14 for AD; OR = 0.99, p = 0.69 and OR = 0.97, p = 0.48 for SQ and SC, respectively). Other previously reported association signals on 15q25 and 6p21 were also refined, but no additional loci reached genome-wide significance. In conclusion, a lung cancer GWAS identified a distinct hereditary contribution to adenocarcinoma.",

author = "Landi, {Maria Teresa} and Nilanjan Chatterjee and Kai Yu and Goldin, {Lynn R.} and Goldstein, {Alisa M.} and Melissa Rotunno and Lisa Mirabello and Kevin Jacobs and William Wheeler and Meredith Yeager and Bergen, {Andrew W.} and Qizhai Li and Dario Consonni and Pesatori, {Angela C.} and Sholom Wacholder and Michael Thun and Ryan Diver and Martin Oken and Jarmo Virtamo and Demetrius Albanes and Zhaoming Wang and Laurie Burdette and Doheny, {Kimberly F.} and Pugh, {Elizabeth W.} and Cathy Laurie and Paul Brennan and Rayjean Hung and Valerie Gaborieau and McKay, {James D.} and Mark Lathrop and John McLaughlin and Ying Wang and Tsao, {Ming Sound} and Spitz, {Margaret R.} and Yufei Wang and Hans Krokan and Lars Vatten and Frank Skorpen and Egil Arnesen and Simone Benhamou and Christine Bouchard and Andres Metsapalu and Tonu Vooder and Mari Nelis and Kristian V{\"a}lk and Field, {John K.} and Chu Chen and Gary Goodman and Patrick Sulem and Gudmar Thorleifsson and Thorunn Rafnar and Timothy Eisen and Wiebke Sauter and Albert Rosenberger and Heike Bickeb{\"o}ller and Angela Risch and Jenny Chang-Claude and Wichmann, {H. Erich} and Kari Stefansson and Richard Houlston and Amos, {Christopher I.} and Fraumeni, {Joseph F.} and Savage, {Sharon A.} and Bertazzi, {Pier Alberto} and Tucker, {Margaret A.} and Stephen Chanock and Caporaso, {Neil E.}",

year = "2009",

month = nov,

day = "13",

doi = "10.1016/j.ajhg.2009.09.012",

language = "English (US)",

volume = "85",

pages = "679--691",

journal = "American journal of human genetics",

issn = "0002-9297",

publisher = "Cell Press",

number = "5",

}

TY - JOUR

T1 - A Genome-wide Association Study of Lung Cancer Identifies a Region of Chromosome 5p15 Associated with Risk for Adenocarcinoma

AU - Landi, Maria Teresa

AU - Chatterjee, Nilanjan

AU - Yu, Kai

AU - Goldin, Lynn R.

AU - Goldstein, Alisa M.

AU - Rotunno, Melissa

AU - Mirabello, Lisa

AU - Jacobs, Kevin

AU - Wheeler, William

AU - Yeager, Meredith

AU - Bergen, Andrew W.

AU - Li, Qizhai

AU - Consonni, Dario

AU - Pesatori, Angela C.

AU - Wacholder, Sholom

AU - Thun, Michael

AU - Diver, Ryan

AU - Oken, Martin

AU - Virtamo, Jarmo

AU - Albanes, Demetrius

AU - Wang, Zhaoming

AU - Burdette, Laurie

AU - Doheny, Kimberly F.

AU - Pugh, Elizabeth W.

AU - Laurie, Cathy

AU - Brennan, Paul

AU - Hung, Rayjean

AU - Gaborieau, Valerie

AU - McKay, James D.

AU - Lathrop, Mark

AU - McLaughlin, John

AU - Wang, Ying

AU - Tsao, Ming Sound

AU - Spitz, Margaret R.

AU - Wang, Yufei

AU - Krokan, Hans

AU - Vatten, Lars

AU - Skorpen, Frank

AU - Arnesen, Egil

AU - Benhamou, Simone

AU - Bouchard, Christine

AU - Metsapalu, Andres

AU - Vooder, Tonu

AU - Nelis, Mari

AU - Välk, Kristian

AU - Field, John K.

AU - Chen, Chu

AU - Goodman, Gary

AU - Sulem, Patrick

AU - Thorleifsson, Gudmar

AU - Rafnar, Thorunn

AU - Eisen, Timothy

AU - Sauter, Wiebke

AU - Rosenberger, Albert

AU - Bickeböller, Heike

AU - Risch, Angela

AU - Chang-Claude, Jenny

AU - Wichmann, H. Erich

AU - Stefansson, Kari

AU - Houlston, Richard

AU - Amos, Christopher I.

AU - Fraumeni, Joseph F.

AU - Savage, Sharon A.

AU - Bertazzi, Pier Alberto

AU - Tucker, Margaret A.

AU - Chanock, Stephen

AU - Caporaso, Neil E.

PY - 2009/11/13

Y1 - 2009/11/13

N2 - Three genetic loci for lung cancer risk have been identified by genome-wide association studies (GWAS), but inherited susceptibility to specific histologic types of lung cancer is not well established. We conducted a GWAS of lung cancer and its major histologic types, genotyping 515,922 single-nucleotide polymorphisms (SNPs) in 5739 lung cancer cases and 5848 controls from one population-based case-control study and three cohort studies. Results were combined with summary data from ten additional studies, for a total of 13,300 cases and 19,666 controls of European descent. Four studies also provided histology data for replication, resulting in 3333 adenocarcinomas (AD), 2589 squamous cell carcinomas (SQ), and 1418 small cell carcinomas (SC). In analyses by histology, rs2736100 (TERT), on chromosome 5p15.33, was associated with risk of adenocarcinoma (odds ratio [OR] = 1.23, 95% confidence interval [CI] = 1.13-1.33, p = 3.02 × 10-7), but not with other histologic types (OR = 1.01, p = 0.84 and OR = 1.00, p = 0.93 for SQ and SC, respectively). This finding was confirmed in each replication study and overall meta-analysis (OR = 1.24, 95% CI = 1.17-1.31, p = 3.74 × 10-14 for AD; OR = 0.99, p = 0.69 and OR = 0.97, p = 0.48 for SQ and SC, respectively). Other previously reported association signals on 15q25 and 6p21 were also refined, but no additional loci reached genome-wide significance. In conclusion, a lung cancer GWAS identified a distinct hereditary contribution to adenocarcinoma.

AB - Three genetic loci for lung cancer risk have been identified by genome-wide association studies (GWAS), but inherited susceptibility to specific histologic types of lung cancer is not well established. We conducted a GWAS of lung cancer and its major histologic types, genotyping 515,922 single-nucleotide polymorphisms (SNPs) in 5739 lung cancer cases and 5848 controls from one population-based case-control study and three cohort studies. Results were combined with summary data from ten additional studies, for a total of 13,300 cases and 19,666 controls of European descent. Four studies also provided histology data for replication, resulting in 3333 adenocarcinomas (AD), 2589 squamous cell carcinomas (SQ), and 1418 small cell carcinomas (SC). In analyses by histology, rs2736100 (TERT), on chromosome 5p15.33, was associated with risk of adenocarcinoma (odds ratio [OR] = 1.23, 95% confidence interval [CI] = 1.13-1.33, p = 3.02 × 10-7), but not with other histologic types (OR = 1.01, p = 0.84 and OR = 1.00, p = 0.93 for SQ and SC, respectively). This finding was confirmed in each replication study and overall meta-analysis (OR = 1.24, 95% CI = 1.17-1.31, p = 3.74 × 10-14 for AD; OR = 0.99, p = 0.69 and OR = 0.97, p = 0.48 for SQ and SC, respectively). Other previously reported association signals on 15q25 and 6p21 were also refined, but no additional loci reached genome-wide significance. In conclusion, a lung cancer GWAS identified a distinct hereditary contribution to adenocarcinoma.

UR - http://www.scopus.com/inward/record.url?scp=72149129508&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=72149129508&partnerID=8YFLogxK

U2 - 10.1016/j.ajhg.2009.09.012

DO - 10.1016/j.ajhg.2009.09.012

M3 - Article

C2 - 19836008

AN - SCOPUS:72149129508

SN - 0002-9297

VL - 85

SP - 679

EP - 691

JO - American journal of human genetics

JF - American journal of human genetics

IS - 5

ER -

A Genome-wide Association Study of Lung Cancer Identifies a Region of Chromosome 5p15 Associated with Risk for Adenocarcinoma

Abstract

ASJC Scopus subject areas

Access to Document

Other files and links

Fingerprint

Cite this