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Familial Aggregation of Common Sequence Variants on 15q24-25.1 in Lung Cancer
Open accessAbstract
Three recent genome-wide association studies identified associations between markers in the chromosomal region 15q24-25.1 and the risk of lung cancer. We conducted a genome-wide association analysis to investigate associations between single-nucleotide polymorphisms (SNPs) and the risk of lung cancer, in which we used blood DNA from 194 case patients with familial lung cancer and 219 cancer-free control subjects. We identified associations between common sequence variants at 15q24-25.1 (that spanned LOC123688 [a hypothetical gene], PSMA4, CHRNA3, CHRNA5, and CHRNB4) and lung cancer. The risk of lung cancer was more than fivefold higher among those subjects who had both a family history of lung cancer and two copies of high-risk alleles rs8034191 (odds ratio [OR] = 7.20, 95% confidence interval [CI] = 2.21 to 23.37) or rs1051730 (OR = 5.67, CI = 2.21 to 14.60, both of which were located in the 15q24-25.1 locus, than among control subjects. Thus, further research to elucidate causal variants in the 15q24-25.1 locus that are associated with lung cancer is warranted.
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“The replicated nicotine dependence loci tagged by rs16969968 (96,100–102) and rs578776 (101,103) have also been reported to influence lung cancer risk in several genome-wide association studies.”
From Nicotine is a selective pharmacological chaperone of acetylcholine receptor number and stoichiometry. Implications for drug discovery (2009) · cites this paper as [103]
In the citing paper
“The replicated nicotine dependence loci tagged by rs16969968 (96,100–102) and rs578776 (101,103) have also been reported to influence lung cancer risk in several genome-wide association studies.”
From Nicotine is a selective pharmacological chaperone of acetylcholine receptor number and stoichiometry. Implications for drug discovery (2009) · cites this paper as [102]
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Self-citationThe 5p15.33 Locus Is Associated with Risk of Lung Adenocarcinoma in Never-Smoking Females in Asia
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“1 (rs16969968 and rs8034191) and 5p15 (rs402710) are associated with lung cancer in the Polish population thereby replicating previous findings [3–9,15–19].”
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“Five candidate SNPs were selected from eight recent GWAS: (1-8) rs402710 (G->A), rs2736100 (C->A), rs4324798 (G->A), rs16969968 (G->A), and rs8034191 (T->C).”
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“CHRNA5 has strong implications in its association with lung cancer [19, 24, 25].”
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Self-citationLangevin, S. M., Ioannidis, J. P. A., Vineis, P., & Taioli, E. (2010) · Pharmacogenetics and Genomics · doi:10.1097/fpc.0b013e32833c3892 · Cited by 34
Rare Variants in Known Susceptibility Loci and Their Contribution to Risk of Lung Cancer
Liu, Y., Lusk, C. M., Cho, M. H., Silverman, E. K., Qiao, D., Zhang, R., Scheurer, M. E., Kheradmand, F., Wheeler, D. A., Tsavachidis, S., et al. (2018) · Journal of Thoracic Oncology · doi:10.1016/j.jtho.2018.06.016 · Cited by 35
“Anderson Cancer Center (n 1⁄4 37) and familial cases from the Genetic Epidemiology of LC Consortium (n 1⁄4 54) (each familial case was chosen from one family considered at high risk of LC and having three or more affected firstdegree members).(5,9) All case patients were white and had histologically confirmed NSCLC.”
Self-citationTargeting lung cancer screening to individuals at greatest risk: the role of genetic factors
Lebrett, M. B., Crosbie, E. J., Smith, M. J., Woodward, E. R., Evans, D. G., & Crosbie, P. A. J. (2021) · Journal of Medical Genetics · doi:10.1136/jmedgenet-2020-107399 · Cited by 34
Rare deleterious germline variants and risk of lung cancer
Liu, Y., Xia, J., McKay, J., Tsavachidis, S., Xiao, X., Spitz, M. R., Cheng, C., Byun, J., Wei, H., Li, Y., et al. (2021) · npj Precision Oncology · doi:10.1038/s41698-021-00146-7 · Cited by 35
Self-citationAcetylcholine receptor pathway in lung cancer: New twists to an old story
Niu, X. (2014) · World Journal of Clinical Oncology · doi:10.5306/wjco.v5.i4.667 · Cited by 36
Wang, T., Chen, T., Thakur, A., Liang, Y., Gao, L., Zhang, S., Tian, Y., Jin, T., Liu, J., & Chen, M. (2015) · Clinical & Translational Oncology · doi:10.1007/s12094-015-1279-x · Cited by 33
Lin, Y., Yu, M., Lin, S., Lee, S., Chen, C., Chen, D., & Chen, P. (2017) · Cancer · doi:10.1002/cncr.30851 · Cited by 33
Kapoor, M., Wang, J., Bertelsen, S. E., Bucholz, K. K., Budde, J., Hinrichs, A. L., Arpana Agrawal, A., Brooks, A. I., Chorlian, D. B., Dick, D. M., et al. (2012) · PLoS ONE · doi:10.1371/journal.pone.0033513 · Cited by 30
“GWAS using several lung cancer populations have also demonstrated association between lung cancer susceptibility and the same or highly correlated variants in the CHRNA5-CHRNA3-CHRNB4 gene cluster [16–18].”
BackgroundCumulative Effect of Multiple Loci on Genetic Susceptibility to Familial Lung Cancer
Liu, P., Vikis, H. G., Lü, Y., Wang, Y., Schwartz, A. G., Pinney, S. M., Yang, P., de Andrade, M., Gazdar, A. F., Gaba, C., et al. (2010) · Cancer Epidemiology Biomarkers & Prevention · doi:10.1158/1055-9965.epi-09-0791 · Cited by 30
“33 with familial lung cancer, we analyzed SNPs within these two chromosomal regions from our previous study (10).”
BackgroundSelf-citationGermline mutations causing familial lung cancer
Tomoshige, K., Matsumoto, K., Tsuchiya, T., Oikawa, M., Miyazaki, T., Yamasaki, N., Mishima, H., Kinoshita, A., Kubo, T., Fukushima, K., et al. (2015) · Journal of Human Genetics · doi:10.1038/jhg.2015.75 · Cited by 29
Genetic variants cis-regulating Xrn2 expression contribute to the risk of spontaneous lung tumor
Lü, Y., Liu, P., James, M. A., Vikis, H. G., Liu, H., Wu, W., Franklin, A. D., & You, M. (2009) · Oncogene · doi:10.1038/onc.2009.396 · Cited by 27
“…leading to a propensity to smoke and develop disease, rather than a direct effect of a genetic susceptibility factor per se (Amos et al., 2008; Liu et al., 2008; Wacholder Received 10 June 2009; revised 24 August 2009; accepted 11 October 2009; published online 16 November 2009…”
BackgroundSelf-citationYu, H., Zhao, H., Wang, L., Han, Y., Chen, W. V., Amos, C. I., Rafnar, Þ., Sulem, P., Stefánsson, K., Landi, M. T., et al. (2011) · DNA repair · doi:10.1016/j.dnarep.2011.01.005 · Cited by 28
“Numerous studies [8–12] have shown that individuals with a familial history of lung cancer have an increased risk, which further supports an etiological role of genetic factors in lung cancer risk.”
BackgroundSelf-citationByun, J., Han, Y., Ostrom, Q. T., Edelson, J. L., Walsh, K. M., Pettit, R. W., Bondy, M. L., Hung, R. J., McKay, J., & Amos, C. I. (2021) · Cancer Epidemiology Biomarkers & Prevention · doi:10.1158/1055-9965.epi-20-1635 · Cited by 28
“GWAS have generally found several loci that predispose for lung cancer across all histologic subtypes, but many more are histology-specific (2, 3).”
BackgroundSelf-citationOkazaki, I., Ishikawa, S., & Sohara, Y. (2014) · PubMed · Cited by 26
Functional characterization of SNPs in CHRNA3/B4 intergenic region associated with drug behaviors
Flora, A. V., Zambrano, C. A., Gallego, X., Miyamoto, J. H., Johnson, K. A., Cowan, K. A., Stitzel, J. A., & Ehringer, M. A. (2013) · Brain Research · doi:10.1016/j.brainres.2013.07.017 · Cited by 27
Liang, Y., Thakur, A., Gao, L., Wang, T., Zhang, S., Ren, H., Meng, J., Geng, T., Jin, T., & Chen, M. (2014) · Tumor Biology · doi:10.1007/s13277-014-2508-6 · Cited by 23
From Nicotine to Breast Cancer, Implications of Cholinergic Receptor Pathway
Linnoila, R. I. (2010) · JNCI Journal of the National Cancer Institute · doi:10.1093/jnci/djq314 · Cited by 22
Human genetic variations: Beacons on the pathways to successful ageing
Cluett, C., & Melzer, D. R. (2009) · Mechanisms of Ageing and Development · doi:10.1016/j.mad.2009.06.009 · Cited by 22
Polymorphisms of CHRNA5-CHRNA3-CHRNB4 Gene Cluster and NSCLC Risk in Chinese Population
Li, Z., Bao, S., Xu, X., Bao, Y., & Zhang, Y. (2012) · Translational Oncology · doi:10.1593/tlo.12304 · Cited by 21
“Recently, the single-nucleotide polymorphisms (SNPs) in CHRNA5 (rs17486278 and rs11637635)–CHRNA3 (rs578776 and rs938682)–CHRNB4 (rs7178270) gene cluster, which is located on chromosome 15q25, were found to be associated with lung cancer in the genome-wide scan in African-Americans and European populations [7,8].”
BackgroundGenome-wide association studies of cancer: principles and potential utility.
Stadler, Z. K., Gallagher, D. J., Thom, P., & Offit, K. (2010) · PubMed · Cited by 21
Biology of Non–Small Cell Lung Cancer
Massion, P. P., & Carbone, D. P. (2010) · Elsevier eBooks · doi:10.1016/b978-1-4160-4710-0.00045-6 · Cited by 21
Chromosome 15q24-25.1 variants, diet, and lung cancer susceptibility in cigarette smokers
Sakoda, L. C., Loomis, M. M., Doherty, J. A., Neuhouser, M. L., Barnett, M. J., Thornquist, M. D., Weiss, N. S., Goodman, G. E., & Chen, C. (2011) · Cancer Causes & Control · doi:10.1007/s10552-010-9716-1 · Cited by 21
“In accord with some studies [2, 3, 5, 8, 9, 11], individual SNP associations persisted after adjusting for smoking quantity.”
ResultSusceptibility loci for lung cancer are associated with mRNA levels of nearby genes in the lung
Nguyen, J. D. U., Lamontagne, M., Couture, C., Conti, M., Paré, P. D., Sin, D. D., Hogg, J. C., Nickle, D. C., Postma, D. S., Timens, W., et al. (2014) · Carcinogenesis · doi:10.1093/carcin/bgu184 · Cited by 19
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Self-citationFrom Smoking to Cancers: Novel Targets to Neuronal Nicotinic Acetylcholine Receptors
Lee, C., Wu, C., & Ho, Y. (2011) · Journal of Oncology · doi:10.1155/2011/693424 · Cited by 20
“A locus in the 15q25 chromosome region was found to be strongly associated with lung cancer [8].”
BackgroundIdentification and validation of PROM1 and CRTC2 mutations in lung cancer patients
He, Y., Li, Y., Qiu, Z., Zhou, B., Shi, S., Zhang, K., Luo, Y., Huang, Q., & Li, W. (2014) · Molecular Cancer · doi:10.1186/1476-4598-13-19 · Cited by 17
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“The remainder of the lung cancer GWAS studies did not implicate any other apoptosis-related gene, though nicotinic acid receptor genes [8], inflammatory genes such as IL1RAP and CRP [9] and a telomerase associated gene TERT [5,10,11] all were significantly associated with lung cancer.”
BackgroundSelf-citationGenetic Epidemiology of Cigarette Smoke–Induced Lung Disease
Schwartz, A. G. (2012) · Proceedings of the American Thoracic Society · doi:10.1513/pats.201106-037ms · Cited by 15
Self-citationZhu, M., Wang, Y., Wang, C., Shen, W., Liu, J., Geng, L., Cheng, Y., Dai, J., Jin, G., Ma, H., et al. (2015) · Scientific Reports · doi:10.1038/srep14969 · Cited by 14
Self-citationAPOBEC3B deletion polymorphism and lung cancer risk in the southern Chinese population
Ben, X., Tian, D., Liang, J., Wu, M., Xie, F., Zheng, J., Chen, J., Fei, Q., Guo, X., Weng, X., et al. (2021) · Annals of Translational Medicine · doi:10.21037/atm-21-989 · Cited by 12
“Furthermore, there is also a genetic component to lung cancer (4), and heritability estimates of the genetic risk for lung cancer are approximately 8% (5).”
CHRNA5 variants related to nicotine sensitivity in lung cancer in vitro
Sun, H., An, L., Zhao, Y., Ma, X., Wang, Y., Jia, Y., Zheng, Y., & Xiao, D. (2010) · International Conference on Biomedical Engineering and Informatics (BMEI) · doi:10.1109/bmei.2010.5639447 · Cited by 11
“However, the consequences of the a5 knockout are not as dramatic as those caused by the loss of other nicotinic receptor subunits [12], resulting in most investigation of AChRs focusing on other subunits [13-15].”
BackgroundSelf-citationCHRNA3 genetic polymorphism and the risk of lung cancer in the Chinese Han smoking population
Zhou, W., Geng, T., Wang, H., Xun, X., Feng, T., Zou, H., Kang, L., Jin, T., & Chen, C. (2015) · Tumor Biology · doi:10.1007/s13277-015-3149-0 · Cited by 12
“Recently, several genome-wide association (GWA) studies mapped a lung cancer susceptibility locus to chromosome 15q25, which contains the CHRNA3, CHRNA5, and CHRN A4 [4–7].”
BackgroundAnnotation and extraction of age and temporally-related events from clinical histories
Hong, J. H., Davoudi, A., Yu, S., & Mowery, D. L. (2020) · BMC Medical Informatics and Decision Making · doi:10.1186/s12911-020-01333-5 · Cited by 12
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Self-citationKim, J. S., Cho, M. S., Nam, J. H., Kim, H. J., Choi, K., & Ryu, J. (2017) · PLoS ONE · doi:10.1371/journal.pone.0177015 · Cited by 11
Metadata
- Authors
- Liu, P., Vikis, H. G., Wang, D., Lu, Y., Wang, Y., Schwartz, A. G., Pinney, S. M., Yang, P., de Andrade, M., Petersen, G. M., Wiest, J. S., Fain, P. R., Gazdar, A., Gaba, C., Rothschild, H., Mandal, D., Coons, T., Lee, J., Kupert, E., Seminara, D., Minna, J., Bailey-Wilson, J. E., Wu, X., Spitz, M. R., Eisen, T., Houlston, R. S., Amos, C. I., Anderson, M. W., & You, M.
- Affiliations
- Washington University in St. Louis (US)
- Institute of Cancer Research (GB)
- ORCID
- Venue
- JNCI: Journal of the National Cancer Institute
- Publisher
- Oxford University Press (OUP)
- Published
- 2008-09
- Volume
- 100
- Issue
- 18
- Pages
- 1326-1330
- ISSN
- 0027-8874 (ISSN-L)
- 1460-2105
- PMC
- PMC2538550
- OpenAlex
- W2168393969
- Cited by
- 154
- References
- 21
- Citations by year
- 2026: 2 · 2025: 3 · 2024: 2 · 2023: 4 · 2022: 4 · 2021: 5 · 2020: 2 · 2019: 6 · 2018: 7 · 2017: 7 · 2016: 8 · 2015: 13 · 2014: 11 · 2013: 6 · 2012: 12
- FWCI
- 11.62
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- JNCI Journal of the National Cancer Institute (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- HighWire Press Open Archive (submittedVersion)
- Funders
- National Institutes of Health (n01hg065404-006, n01pc35145-19-0-7)
- National Human Genome Research Institute (N01HG65404)
- National Cancer Institute (R01CA127219, R01CA80127, R01CA093643, P30CA 22453, R01 CA 55769, (P50-CA70907, R01CA099187, R01CA063700, R01CA080127, U01CA076293, R01CA133996, U01CA76293, N01 PC 35145, R01CA055769, R01CA099147, R01CA058554, P50CA070907, R01CA63700, R01CA121197, P30CA022453)
- National Institute of Environmental Health Sciences (R01ES012063, P30ES006096, R01ES013340, P30 ES-06096)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic Associations and Epidemiology
- Health Sciences › Medicine › Oncology › Lung Cancer Research Studies
- Health Sciences › Medicine › Public Health, Environmental and Occupational Health › Smoking Behavior and Cessation
- Keywords
- lung cancer, familial aggregation, single nucleotide polymorphisms, genetic susceptibility, rs1051730, CHRNA3, CHRNA5, CHRNB4, PSMA4, family history of cancer
- MeSH terms
- Chromosomes, Human, Pair 15, DNA, Neoplasm, Genotype, Humans, Lung Neoplasms, Research Design, Smoking, Confounding Factors, Epidemiologic, Case-Control Studies, Sequence Analysis, DNA, Genetic Predisposition to Disease, Polymorphism, Single Nucleotide
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