Replication of Lung Cancer Susceptibility Loci at Chromosomes 15q25, 5p15, and 6p21: A Pooled Analysis From the International Lung Cancer Consortium
Open accessAbstract
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 11 645 lung cancer case patients and 14 954 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, P(trend) = 2 x 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, P(trend) = 1 x 10(-10)) and rs402710 (OR = 1.14, 95% CI = 1.09 to 1.19, P(trend) = 5 x 10(-8)) and identified similar associations in Asians (rs2736100: OR = 1.23, 95% CI = 1.12 to 1.35, P(trend) = 2 x 10(-5); rs402710: OR = 1.15, 95% CI = 1.04 to 1.27, P(trend) = .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. CONCLUSIONS: In 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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“A recent study showed that Chrna5 null mice had higher nicotine intake due to loss of an inhibitory effect on brain reward systems. 107”
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- Authors
- Truong, T., Hung, R. J., Amos, C. I., Wu, X., Bickeböller, H., Rosenberger, A., Sauter, W., Illig, T., Wichmann, H.-E., Risch, A., Dienemann, H., Kaaks, R., Yang, P., Jiang, R., Wiencke, J. K., Wrensch, M., Hansen, H., Kelsey, K. T., Matsuo, K., Tajima, K., Schwartz, A. G., Wenzlaff, A., Seow, A., Ying, C., Staratschek-Jox, A., Nürnberg, P., Stoelben, E., Wolf, J., Lazarus, P., Muscat, J. E., Gallagher, C. J., Zienolddiny, S., Haugen, A., van der Heijden, H. F. M., Kiemeney, L. A., Isla, D., Mayordomo, J. I., Rafnar, T., Stefansson, K., Zhang, Z.-F., Chang, S.-C., Kim, J. H., Hong, Y.-C., Duell, E. J., Andrew, A. S., Lejbkowicz, F., Rennert, G., Müller, H., Brenner, H., Le Marchand, L., Benhamou, S., Bouchardy, C., Teare, M. D., Xue, X., McLaughlin, J., Liu, G., McKay, J. D., Brennan, P., & Spitz, M. R.
- ORCID
- Hung, Rayjean J.
- Amos, Christopher I.
- Wu, Xifeng
- Bickeböller, Heike
- Rosenberger, Albert
- Wichmann, H.-Erich
- Risch, Angela
- Yang, Ping
- Jiang, Ruoxiang
- Wiencke, John K.
- Wrensch, Margaret
- Hansen, Helen
- Kelsey, Karl T.
- Matsuo, Keitaro
- Schwartz, Ann G.
- Seow, Adeline
- Nürnberg, Peter
- Stoelben, Erich
- Wolf, Jürgen
- Lazarus, Philip
- Muscat, Joshua E.
- Zienolddiny, Shanbeh
- Haugen, Aage
- Kiemeney, Lambertus A.
- Isla, Dolores
- Mayordomo, Jose Ignacio
- Zhang, Zuo-Feng
- Chang, Shen-Chih
- Kim, Jin Hee
- Hong, Yun-Chul
- Duell, Eric J.
- Andrew, Angeline S.
- Rennert, Gad
- Müller, Heiko
- Brenner, Hermann
- Benhamou, Simone
- Bouchardy, Christine
- Teare, M. Dawn
- Xue, Xiaoyan
- McLaughlin, John
- Liu, Geoffrey
- McKay, James D.
- Brennan, Paul
- Venue
- JNCI: Journal of the National Cancer Institute
- Publisher
- Oxford University Press (OUP)
- Published
- 2010-07-07
- Volume
- 102
- Issue
- 13
- Pages
- 959-971
- ISSN
- 0027-8874 (ISSN-L)
- 1460-2105
- PMC
- PMC2897877
- OpenAlex
- W2112488127
- Cited by
- 194
- References
- 46
- Citations by year
- 2026: 2 · 2025: 2 · 2024: 5 · 2023: 8 · 2022: 5 · 2021: 6 · 2020: 5 · 2019: 5 · 2018: 5 · 2017: 13 · 2016: 14 · 2015: 18 · 2014: 22 · 2013: 21 · 2012: 34
- FWCI
- 15.09
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- JNCI Journal of the National Cancer Institute (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- reroDoc Digital Library (submittedVersion)
- National University of Singapore (submittedVersion)
- GoeScholar The Publication Server of the Georg-August-Universität Göttingen (Georg-August-Universität Göttingen) (submittedVersion, cc-by)
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- Site cant be reached (submittedVersion)
- Radboud Repository (Radboud University) (submittedVersion)
- Seoul National University Open Repository (Seoul National University) (submittedVersion)
- Funders
- National Institutes of Health (5r03ca133939-02, 5r01ca055874-05, 5r01ca090833-09, 5p20rr018787-07)
- National Institute on Drug Abuse (DA 11386, R01DA011386)
- National Cancer Institute (CA55874, R01CA127219, CA77118, R01CA085997, R03 CA133939-01, CA55769, CA09142, CA133996, T32CA009142, P01CA68384, K99CA131477, CA80127, CA 90833, R01CA092039, R01CA080127, CA85997, P01CA068384, R01CA133996, CA121197, R01CA055769, CA84354, R01CA084354, R01CA121197, R03CA077118, K07CA104231, CA127219)
- National Institute of Environmental Health Sciences (ES06717, R01ES006717, ES011667, R21ES011667)
- National Center for Research Resources (P20-RR018787)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic Associations and Epidemiology
- Health Sciences › Medicine › Oncology › Lung Cancer Research Studies
- Health Sciences › Medicine › Physiology › Smoking Behavior and Cessation
- Keywords
- lung cancer susceptibility, chromosome 15q25, chromosome 6p21, single nucleotide polymorphisms, replication of genetic associations, ever-smokers, never smokers, Asian populations, rs16969968, rs2736100, age at diagnosis
- MeSH terms
- Adenocarcinoma, Adult, Aged, Aged, 80 and over, Canada, Carcinoma, Squamous Cell, Chromosomes, Human, Pair 15, Chromosomes, Human, Pair 5, Chromosomes, Human, Pair 6, Europe, Female, Gene Frequency, Genotype, Homozygote, Humans, International Cooperation, Japan, Korea, Lung Neoplasms, Male, Middle Aged, Quality Control, Risk Factors, Singapore, Smoking, Tobacco Use Disorder, United States, Linkage Disequilibrium, Odds Ratio, Case-Control Studies, Carcinoma, Large Cell, Carcinoma, Small Cell, Risk Assessment, Genetic Predisposition to Disease, Polymorphism, Single Nucleotide, White People, Asian People, Genome-Wide Association Study, Genetic Association Studies
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