Replication of lung cancer susceptibility loci at chromosomes 15q25, 5p15, and 6p21

A pooled analysis from the international lung cancer consortium

Therese Truong, Rayjean J. Hung, Christopher I. Amos, Xifeng Wu, Heike Bickeböller, Albert Rosenberger, Wiebke Sauter, Thomas Illig, H. Erich Wichmann, Angela Risch, Hendrik Dienemann, Rudolph Kaaks, Ping Yang, Ruoxiang Jiang, John K. Wiencke, Margaret Wrensch, Helen Hansen, Karl T. Kelsey, Keitaro Matsuo, Kazuo Tajima & 39 others Ann G. Schwartz, Angie Wenzlaff, Adeline Seow, Chen Ying, Andrea Staratschek-Jox, Peter Nürnberg, Erich Stoelben, Jürgen Wolf, Philip Lazarus, Joshua Muscat, Carla J. Gallagher, Shanbeh Zienolddiny, Aage Haugen, Henricus F.M. Van Der Heijden, Lambertus A. Kiemeney, Dolores Isla, Jose Ignacio Mayordomo, Thorunn Rafnar, Kari Stefansson, Zuo Feng Zhang, Shen Chih Chang, Jin Hee Kim, Yun Chul Hong, Eric J. Duell, Angeline S. Andrew, Flavio Lejbkowicz, Gad Rennert, Heiko Müller, Hermann Brenner, Loïc Le Marchand, Simone Benhamou, Christine Bouchardy, M. Dawn Teare, Xiaoyan Xue, John McLaughlin, Geoffrey Liu, James D. McKay, Paul Brennan, Margaret R. Spitz

Research output: Contribution to journalArticle

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Abstract

Background Genome-wide association studies have identified three chromosomal regions at 15q25, 5p15, and 6p21 as being associated with the risk of lung cancer. To confirm these associations in independent studies and investigate heterogeneity of these associations within specific subgroups, we conducted a coordinated genotyping study within the International Lung Cancer Consortium based on independent studies that were not included in previous genome-wide association studies. Methods Genotype data for single-nucleotide polymorphisms at chromosomes 15q25 (rs16969968, rs8034191), 5p15 (rs2736100, rs402710), and 6p21 (rs2256543, rs4324798) from 21 case-control studies for 11645 lung cancer case patients and 14954 control subjects, of whom 85% were white and 15% were Asian, were pooled. Associations between the variants and the risk of lung cancer were estimated by logistic regression models. All statistical tests were two-sided. Results Associations between 15q25 and the risk of lung cancer were replicated in white ever-smokers (rs16969968: odds ratio [OR] = 1.26, 95% confidence interval [CI] = 1.21 to 1.32, Ptrend = 2 × 10-26), and this association was stronger for those diagnosed at younger ages. There was no association in never-smokers or in Asians between either of the 15q25 variants and the risk of lung cancer. For the chromosome 5p15 region, we confirmed statistically significant associations in whites for both rs2736100 (OR = 1.15, 95% CI = 1.10 to 1.20, Ptrend = 1 × 10 -10) and rs402710 (OR = 1.14, 95% CI = 1.09 to 1.19, Ptrend = 5 × 10-8) and identified similar associations in Asians (rs2736100: OR = 1.23, 95% CI = 1.12 to 1.35, Ptrend = 2 × 10 -5; rs402710: OR = 1.15, 95% CI = 1.04 to 1.27, Ptrend =. 007). The associations between the 5p15 variants and lung cancer differed by histology; odds ratios for rs2736100 were highest in adenocarcinoma and for rs402710 were highest in adenocarcinoma and squamous cell carcinomas. This pattern was observed in both ethnic groups. Neither of the two variants on chromosome 6p21 was associated with the risk of lung cancer. Conclusion sIn this international genetic association study of lung cancer, previous associations found in white populations were replicated and new associations were identified in Asian populations. Future genetic studies of lung cancer should include detailed stratification by histology.

Original languageEnglish (US)
Pages (from-to)959-971
Number of pages13
JournalJournal of the National Cancer Institute
Volume102
Issue number13
DOIs
StatePublished - Jul 1 2010

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Lung Neoplasms
Chromosomes
Odds Ratio
Confidence Intervals
Genome-Wide Association Study
Histology
Adenocarcinoma
Logistic Models
Genetic Association Studies
Ethnic Groups
Population
Single Nucleotide Polymorphism
Case-Control Studies
Squamous Cell Carcinoma
Genotype

All Science Journal Classification (ASJC) codes

  • Oncology
  • Cancer Research

Cite this

Truong, Therese ; Hung, Rayjean J. ; Amos, Christopher I. ; Wu, Xifeng ; Bickeböller, Heike ; Rosenberger, Albert ; Sauter, Wiebke ; Illig, Thomas ; Wichmann, H. Erich ; Risch, Angela ; Dienemann, Hendrik ; Kaaks, Rudolph ; Yang, Ping ; Jiang, Ruoxiang ; Wiencke, John K. ; Wrensch, Margaret ; Hansen, Helen ; Kelsey, Karl T. ; Matsuo, Keitaro ; Tajima, Kazuo ; Schwartz, Ann G. ; Wenzlaff, Angie ; Seow, Adeline ; Ying, Chen ; Staratschek-Jox, Andrea ; Nürnberg, Peter ; Stoelben, Erich ; Wolf, Jürgen ; Lazarus, Philip ; Muscat, Joshua ; Gallagher, Carla J. ; Zienolddiny, Shanbeh ; Haugen, Aage ; Van Der Heijden, Henricus F.M. ; Kiemeney, Lambertus A. ; Isla, Dolores ; Mayordomo, Jose Ignacio ; Rafnar, Thorunn ; Stefansson, Kari ; Zhang, Zuo Feng ; Chang, Shen Chih ; Kim, Jin Hee ; Hong, Yun Chul ; Duell, Eric J. ; Andrew, Angeline S. ; Lejbkowicz, Flavio ; Rennert, Gad ; Müller, Heiko ; Brenner, Hermann ; Le Marchand, Loïc ; Benhamou, Simone ; Bouchardy, Christine ; Teare, M. Dawn ; Xue, Xiaoyan ; McLaughlin, John ; Liu, Geoffrey ; McKay, James D. ; Brennan, Paul ; Spitz, Margaret R. / Replication of lung cancer susceptibility loci at chromosomes 15q25, 5p15, and 6p21 : A pooled analysis from the international lung cancer consortium. In: Journal of the National Cancer Institute. 2010 ; Vol. 102, No. 13. pp. 959-971.
@article{efa460339c604ccba24858d471c2a63c,
title = "Replication of lung cancer susceptibility loci at chromosomes 15q25, 5p15, and 6p21: A pooled analysis from the international lung cancer consortium",
abstract = "Background Genome-wide association studies have identified three chromosomal regions at 15q25, 5p15, and 6p21 as being associated with the risk of lung cancer. To confirm these associations in independent studies and investigate heterogeneity of these associations within specific subgroups, we conducted a coordinated genotyping study within the International Lung Cancer Consortium based on independent studies that were not included in previous genome-wide association studies. Methods Genotype data for single-nucleotide polymorphisms at chromosomes 15q25 (rs16969968, rs8034191), 5p15 (rs2736100, rs402710), and 6p21 (rs2256543, rs4324798) from 21 case-control studies for 11645 lung cancer case patients and 14954 control subjects, of whom 85{\%} were white and 15{\%} were Asian, were pooled. Associations between the variants and the risk of lung cancer were estimated by logistic regression models. All statistical tests were two-sided. Results Associations between 15q25 and the risk of lung cancer were replicated in white ever-smokers (rs16969968: odds ratio [OR] = 1.26, 95{\%} confidence interval [CI] = 1.21 to 1.32, Ptrend = 2 × 10-26), and this association was stronger for those diagnosed at younger ages. There was no association in never-smokers or in Asians between either of the 15q25 variants and the risk of lung cancer. For the chromosome 5p15 region, we confirmed statistically significant associations in whites for both rs2736100 (OR = 1.15, 95{\%} CI = 1.10 to 1.20, Ptrend = 1 × 10 -10) and rs402710 (OR = 1.14, 95{\%} CI = 1.09 to 1.19, Ptrend = 5 × 10-8) and identified similar associations in Asians (rs2736100: OR = 1.23, 95{\%} CI = 1.12 to 1.35, Ptrend = 2 × 10 -5; rs402710: OR = 1.15, 95{\%} CI = 1.04 to 1.27, Ptrend =. 007). The associations between the 5p15 variants and lung cancer differed by histology; odds ratios for rs2736100 were highest in adenocarcinoma and for rs402710 were highest in adenocarcinoma and squamous cell carcinomas. This pattern was observed in both ethnic groups. Neither of the two variants on chromosome 6p21 was associated with the risk of lung cancer. Conclusion sIn this international genetic association study of lung cancer, previous associations found in white populations were replicated and new associations were identified in Asian populations. Future genetic studies of lung cancer should include detailed stratification by histology.",
author = "Therese Truong and Hung, {Rayjean J.} and Amos, {Christopher I.} and Xifeng Wu and Heike Bickeb{\"o}ller and Albert Rosenberger and Wiebke Sauter and Thomas Illig and Wichmann, {H. Erich} and Angela Risch and Hendrik Dienemann and Rudolph Kaaks and Ping Yang and Ruoxiang Jiang and Wiencke, {John K.} and Margaret Wrensch and Helen Hansen and Kelsey, {Karl T.} and Keitaro Matsuo and Kazuo Tajima and Schwartz, {Ann G.} and Angie Wenzlaff and Adeline Seow and Chen Ying and Andrea Staratschek-Jox and Peter N{\"u}rnberg and Erich Stoelben and J{\"u}rgen Wolf and Philip Lazarus and Joshua Muscat and Gallagher, {Carla J.} and Shanbeh Zienolddiny and Aage Haugen and {Van Der Heijden}, {Henricus F.M.} and Kiemeney, {Lambertus A.} and Dolores Isla and Mayordomo, {Jose Ignacio} and Thorunn Rafnar and Kari Stefansson and Zhang, {Zuo Feng} and Chang, {Shen Chih} and Kim, {Jin Hee} and Hong, {Yun Chul} and Duell, {Eric J.} and Andrew, {Angeline S.} and Flavio Lejbkowicz and Gad Rennert and Heiko M{\"u}ller and Hermann Brenner and {Le Marchand}, Lo{\"i}c and Simone Benhamou and Christine Bouchardy and Teare, {M. Dawn} and Xiaoyan Xue and John McLaughlin and Geoffrey Liu and McKay, {James D.} and Paul Brennan and Spitz, {Margaret R.}",
year = "2010",
month = "7",
day = "1",
doi = "10.1093/jnci/djq178",
language = "English (US)",
volume = "102",
pages = "959--971",
journal = "Journal of the National Cancer Institute",
issn = "0027-8874",
publisher = "Oxford University Press",
number = "13",

}

Truong, T, Hung, RJ, Amos, CI, Wu, X, Bickeböller, H, Rosenberger, A, Sauter, W, Illig, T, Wichmann, HE, Risch, A, Dienemann, H, Kaaks, R, Yang, P, Jiang, R, Wiencke, JK, Wrensch, M, Hansen, H, Kelsey, KT, Matsuo, K, Tajima, K, Schwartz, AG, Wenzlaff, A, Seow, A, Ying, C, Staratschek-Jox, A, Nürnberg, P, Stoelben, E, Wolf, J, Lazarus, P, Muscat, J, Gallagher, CJ, Zienolddiny, S, Haugen, A, Van Der Heijden, HFM, Kiemeney, LA, Isla, D, Mayordomo, JI, Rafnar, T, Stefansson, K, Zhang, ZF, Chang, SC, Kim, JH, Hong, YC, Duell, EJ, Andrew, AS, Lejbkowicz, F, Rennert, G, Müller, H, Brenner, H, Le Marchand, L, Benhamou, S, Bouchardy, C, Teare, MD, Xue, X, McLaughlin, J, Liu, G, McKay, JD, Brennan, P & Spitz, MR 2010, 'Replication of lung cancer susceptibility loci at chromosomes 15q25, 5p15, and 6p21: A pooled analysis from the international lung cancer consortium', Journal of the National Cancer Institute, vol. 102, no. 13, pp. 959-971. https://doi.org/10.1093/jnci/djq178

Replication of lung cancer susceptibility loci at chromosomes 15q25, 5p15, and 6p21 : A pooled analysis from the international lung cancer consortium. / Truong, Therese; Hung, Rayjean J.; Amos, Christopher I.; Wu, Xifeng; Bickeböller, Heike; Rosenberger, Albert; Sauter, Wiebke; Illig, Thomas; Wichmann, H. Erich; Risch, Angela; Dienemann, Hendrik; Kaaks, Rudolph; Yang, Ping; Jiang, Ruoxiang; Wiencke, John K.; Wrensch, Margaret; Hansen, Helen; Kelsey, Karl T.; Matsuo, Keitaro; Tajima, Kazuo; Schwartz, Ann G.; Wenzlaff, Angie; Seow, Adeline; Ying, Chen; Staratschek-Jox, Andrea; Nürnberg, Peter; Stoelben, Erich; Wolf, Jürgen; Lazarus, Philip; Muscat, Joshua; Gallagher, Carla J.; Zienolddiny, Shanbeh; Haugen, Aage; Van Der Heijden, Henricus F.M.; Kiemeney, Lambertus A.; Isla, Dolores; Mayordomo, Jose Ignacio; Rafnar, Thorunn; Stefansson, Kari; Zhang, Zuo Feng; Chang, Shen Chih; Kim, Jin Hee; Hong, Yun Chul; Duell, Eric J.; Andrew, Angeline S.; Lejbkowicz, Flavio; Rennert, Gad; Müller, Heiko; Brenner, Hermann; Le Marchand, Loïc; Benhamou, Simone; Bouchardy, Christine; Teare, M. Dawn; Xue, Xiaoyan; McLaughlin, John; Liu, Geoffrey; McKay, James D.; Brennan, Paul; Spitz, Margaret R.

In: Journal of the National Cancer Institute, Vol. 102, No. 13, 01.07.2010, p. 959-971.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Replication of lung cancer susceptibility loci at chromosomes 15q25, 5p15, and 6p21

T2 - A pooled analysis from the international lung cancer consortium

AU - Truong, Therese

AU - Hung, Rayjean J.

AU - Amos, Christopher I.

AU - Wu, Xifeng

AU - Bickeböller, Heike

AU - Rosenberger, Albert

AU - Sauter, Wiebke

AU - Illig, Thomas

AU - Wichmann, H. Erich

AU - Risch, Angela

AU - Dienemann, Hendrik

AU - Kaaks, Rudolph

AU - Yang, Ping

AU - Jiang, Ruoxiang

AU - Wiencke, John K.

AU - Wrensch, Margaret

AU - Hansen, Helen

AU - Kelsey, Karl T.

AU - Matsuo, Keitaro

AU - Tajima, Kazuo

AU - Schwartz, Ann G.

AU - Wenzlaff, Angie

AU - Seow, Adeline

AU - Ying, Chen

AU - Staratschek-Jox, Andrea

AU - Nürnberg, Peter

AU - Stoelben, Erich

AU - Wolf, Jürgen

AU - Lazarus, Philip

AU - Muscat, Joshua

AU - Gallagher, Carla J.

AU - Zienolddiny, Shanbeh

AU - Haugen, Aage

AU - Van Der Heijden, Henricus F.M.

AU - Kiemeney, Lambertus A.

AU - Isla, Dolores

AU - Mayordomo, Jose Ignacio

AU - Rafnar, Thorunn

AU - Stefansson, Kari

AU - Zhang, Zuo Feng

AU - Chang, Shen Chih

AU - Kim, Jin Hee

AU - Hong, Yun Chul

AU - Duell, Eric J.

AU - Andrew, Angeline S.

AU - Lejbkowicz, Flavio

AU - Rennert, Gad

AU - Müller, Heiko

AU - Brenner, Hermann

AU - Le Marchand, Loïc

AU - Benhamou, Simone

AU - Bouchardy, Christine

AU - Teare, M. Dawn

AU - Xue, Xiaoyan

AU - McLaughlin, John

AU - Liu, Geoffrey

AU - McKay, James D.

AU - Brennan, Paul

AU - Spitz, Margaret R.

PY - 2010/7/1

Y1 - 2010/7/1

N2 - Background Genome-wide association studies have identified three chromosomal regions at 15q25, 5p15, and 6p21 as being associated with the risk of lung cancer. To confirm these associations in independent studies and investigate heterogeneity of these associations within specific subgroups, we conducted a coordinated genotyping study within the International Lung Cancer Consortium based on independent studies that were not included in previous genome-wide association studies. Methods Genotype data for single-nucleotide polymorphisms at chromosomes 15q25 (rs16969968, rs8034191), 5p15 (rs2736100, rs402710), and 6p21 (rs2256543, rs4324798) from 21 case-control studies for 11645 lung cancer case patients and 14954 control subjects, of whom 85% were white and 15% were Asian, were pooled. Associations between the variants and the risk of lung cancer were estimated by logistic regression models. All statistical tests were two-sided. Results Associations between 15q25 and the risk of lung cancer were replicated in white ever-smokers (rs16969968: odds ratio [OR] = 1.26, 95% confidence interval [CI] = 1.21 to 1.32, Ptrend = 2 × 10-26), and this association was stronger for those diagnosed at younger ages. There was no association in never-smokers or in Asians between either of the 15q25 variants and the risk of lung cancer. For the chromosome 5p15 region, we confirmed statistically significant associations in whites for both rs2736100 (OR = 1.15, 95% CI = 1.10 to 1.20, Ptrend = 1 × 10 -10) and rs402710 (OR = 1.14, 95% CI = 1.09 to 1.19, Ptrend = 5 × 10-8) and identified similar associations in Asians (rs2736100: OR = 1.23, 95% CI = 1.12 to 1.35, Ptrend = 2 × 10 -5; rs402710: OR = 1.15, 95% CI = 1.04 to 1.27, Ptrend =. 007). The associations between the 5p15 variants and lung cancer differed by histology; odds ratios for rs2736100 were highest in adenocarcinoma and for rs402710 were highest in adenocarcinoma and squamous cell carcinomas. This pattern was observed in both ethnic groups. Neither of the two variants on chromosome 6p21 was associated with the risk of lung cancer. Conclusion sIn this international genetic association study of lung cancer, previous associations found in white populations were replicated and new associations were identified in Asian populations. Future genetic studies of lung cancer should include detailed stratification by histology.

AB - Background Genome-wide association studies have identified three chromosomal regions at 15q25, 5p15, and 6p21 as being associated with the risk of lung cancer. To confirm these associations in independent studies and investigate heterogeneity of these associations within specific subgroups, we conducted a coordinated genotyping study within the International Lung Cancer Consortium based on independent studies that were not included in previous genome-wide association studies. Methods Genotype data for single-nucleotide polymorphisms at chromosomes 15q25 (rs16969968, rs8034191), 5p15 (rs2736100, rs402710), and 6p21 (rs2256543, rs4324798) from 21 case-control studies for 11645 lung cancer case patients and 14954 control subjects, of whom 85% were white and 15% were Asian, were pooled. Associations between the variants and the risk of lung cancer were estimated by logistic regression models. All statistical tests were two-sided. Results Associations between 15q25 and the risk of lung cancer were replicated in white ever-smokers (rs16969968: odds ratio [OR] = 1.26, 95% confidence interval [CI] = 1.21 to 1.32, Ptrend = 2 × 10-26), and this association was stronger for those diagnosed at younger ages. There was no association in never-smokers or in Asians between either of the 15q25 variants and the risk of lung cancer. For the chromosome 5p15 region, we confirmed statistically significant associations in whites for both rs2736100 (OR = 1.15, 95% CI = 1.10 to 1.20, Ptrend = 1 × 10 -10) and rs402710 (OR = 1.14, 95% CI = 1.09 to 1.19, Ptrend = 5 × 10-8) and identified similar associations in Asians (rs2736100: OR = 1.23, 95% CI = 1.12 to 1.35, Ptrend = 2 × 10 -5; rs402710: OR = 1.15, 95% CI = 1.04 to 1.27, Ptrend =. 007). The associations between the 5p15 variants and lung cancer differed by histology; odds ratios for rs2736100 were highest in adenocarcinoma and for rs402710 were highest in adenocarcinoma and squamous cell carcinomas. This pattern was observed in both ethnic groups. Neither of the two variants on chromosome 6p21 was associated with the risk of lung cancer. Conclusion sIn this international genetic association study of lung cancer, previous associations found in white populations were replicated and new associations were identified in Asian populations. Future genetic studies of lung cancer should include detailed stratification by histology.

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U2 - 10.1093/jnci/djq178

DO - 10.1093/jnci/djq178

M3 - Article

VL - 102

SP - 959

EP - 971

JO - Journal of the National Cancer Institute

JF - Journal of the National Cancer Institute

SN - 0027-8874

IS - 13

ER -