Journal of the National Cancer Institute Advance Access originally published online on September 9, 2008
JNCI Journal of the National Cancer Institute 2008 100(18):1326-1330; doi:10.1093/jnci/djn268
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© The Author 2008. Published by Oxford University Press.
BRIEF COMMUNICATION |
Familial Aggregation of Common Sequence Variants on 15q24-25.1 in Lung Cancer
Affiliations of authors: Washington University, St Louis, MO (PL, HGV, DW, YL, YW, MY); Karmanos Cancer Institute, Detroit, MI (AGS); University of Cincinnati, Cincinnati, OH (SMP, JLM, WA); Mayo Clinic, Rochester, MN (PY, MdA, GMP, DS); National Cancer Institute, Bethesda, MD (JSW); University of Colorado, Denver, CO (PRF); University of Texas Southwestern Medical Center, Dallas, TX (AG, JM); University of Toledo College of Medicine, Toledo, OH (CG); Louisiana State University Health Science Center, New Orleans, LA (HR, DM); Saccomanno Research Institute, Grand Junction, CO (TC); National Human Genome Research Institute, Baltimore, MD (JEB-W); M. D. Anderson Cancer Center, Houston, TX (XW, MRS, CIA); Department of Oncology, University of Cambridge, Cambridge, CB2 2RE, UK (TE); Section of Cancer Genetics, Institute of Cancer Research, SM2 5NG, UK (RSH)
Correspondence to: Ming You, MD, PhD, Department of Surgery and The Alvin J. Siteman Cancer Center, Washington University, 660 Euclid Ave, Box 8109, St Louis, MO 63110 (e-mail: youm{at}wudosis.wustl.edu).
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.
| Context and Caveats Prior knowledge Genome-wide association studies have identified associations between markers in the chromosomal region 15q24-25.1 and the risk of lung cancer. Study design A genome-wide case–control association analysis was used to investigate relationships between single-nucleotide polymorphisms (SNPs) and the risk of familial lung cancer. Contribution Subjects with both a family history of lung cancer and two copies of either of two high-risk alleles in 15q24-25.1 had a higher risk of lung cancer than control subjects. Implications Additional research is required to identify which genetic variants in the 15q24-25.1 region are associated with a high risk of lung cancer. Limitations Associations of risk alleles with nicotine dependence were not directly tested because the data were not available. Smoking quantity was available; however, no association between smoking quantity and the high-risk alleles was found. The small sample size may have limited the ability to detect a smaller effect size for risk alleles among heterozygotes with familial lung cancer. From the Editors
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Manuscript received April 2, 2008; revised June 30, 2008; accepted July 2, 2008.
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J Natl Cancer Inst 2008 100: 1269.
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