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 E.
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.
N1 - Funding Information:
US National Institutes of Health (NIH); National Cancer Institute (NCI) (R03 CA133939-01 and R01 CA092039). The individual studies were funded by the following sources: MD Anderson study: NCI (CA55769, CA127219, CA121197, and CA133996); German multicenter study: Lung Cancer in the Young study was partly funded by the Deutsche Forschungsgemeinschaft (DFG; BI 576/2-1 and BI 576/2-2), the genome-wide study was funded by the Helmholtz Association, Germany; the Heidelberg lung cancer study was supported by the Deutsche Krebshilfe; the European Prospective Investigation into Cancer and Nutrition-Heidelberg study was funded by “Europe Against Cancer” Programme of the European Commission (Santé et protection des consommateurs [SANCO]); German Cancer Aid; German Cancer Research Center; German Federal Ministry of Education and Research; Mayo Clinic study: NCI (CA77118, CA80127, and CA84354); University of California, San Francisco study: National Institute of Environmental Health Sciences (ES06717); Aichi study: Scientific Research grant from the Ministry of Education, Science, Sports, Culture and Technology of Japan (17015052) and grant for the Third-Term Comprehensive 10-Year Strategy for Cancer Control from the Ministry of Health, Labor and Welfare of Japan (H20-002); Singapore study: National Medical Research Council, Singapore (NMRC/1075/2006); Norwegian study: The Norwegian Cancer Society; UCLA study: NIH (DA11386, CA90833, CA09142, and ES011667) and the Alper Research Center for Environmental Genomics of the UCLA’s Jonsson Comprehensive Cancer Center; New England Lung Cancer study: National Center for Research Resources, a component of the NIH (P20RR018787); Israel study: United States–Israel Binational Science Foundation (BSF) (2003159); Penn State study: NCI (PO1 CA68384, K07 CA104231, and K99CA131477) and PA-DOH 4100038714 and PA-DOH 4100038715 from the Pennsylvania Department of Health; Saarland study: Baden-Württemberg Ministry of Research, Science and Arts; Cologne study: this study was funded by the Helmholtz Association, Germany, through VH.VI-143 and by the Monika Kutzner Stiftung; University of Hawaii Study: NCI (CA55874 and CA85997); Toronto study: Canadian Cancer Society (20214).
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
C2 - 20548021
AN - SCOPUS:77954715678
SN - 0027-8874
VL - 102
SP - 959
EP - 971
JO - Journal of the National Cancer Institute
JF - Journal of the National Cancer Institute
IS - 13
ER -