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J Natl Cancer Inst. 2014 Apr;106(4):dju061. doi: 10.1093/jnci/dju061. Epub 2014 Mar 28.

Pleiotropic associations of risk variants identified for other cancers with lung cancer risk: the PAGE and TRICL consortia.

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  • 1Affiliations of authors: Department of Preventive Medicine, Norris Comprehensive Cancer Center, Keck School of Medicine, University of Southern California, Los Angeles, CA (SLP, FRS, CAH); Public Health Sciences Division, Fred Hutchinson Cancer Research Center, Seattle, WA (MDF, JMK, AY, YL, UP, CC, CK); Colon Cancer Genetics Group, Institute of Genetics and Molecular Medicine, University of Edinburgh and Medical Research Council Human Genetics Unit, Edinburgh, UK (MT); Epidemiology Program, University of Hawaii Cancer Center, Honolulu, HI (CPC, LRW, LL); Community and Family Medicine, Geisel School of Medicine, Dartmouth College, Hanover, NH (YH, CIA); Department of Epidemiology (S-AL, AB, KEN, GH) and Carolina Center for Genome Sciences (KEN), University of North Carolina, Chapel Hill, NC; Molecular Physiology and Biophysics (LD, DCC), Center for Human Genetics Research (LD, RG, HD, DCC, WSB), Vanderbilt Epidemiology Center (JHF), and Biomedical Informatics (WSB), Vanderbilt University, Nashville, TN; Division of Genomic Medicine, National Human Genome Research Institute (LH), and Division of Cancer Epidemiology and Genetics, National Cancer Institute (DA, NC, MTL), National Institutes of Health, Bethesda, MD; Department of Statistics and Biostatistics, Rutgers University, Piscataway, NJ (SB); Information Sciences Institute, University of Southern California, Marina del Rey, CA (ED); Department of Oncology, School of Medicine, Wayne State University, Detroit, Michigan (MLC); M.D. Anderson Cancer Center, Houston, TX (WC, MP); Harvard University School of Public Health, Boston, MA (DCC); Roy Castle Lung Cancer Research Programme, Department of Molecular and Clinical Cancer Medicine, The University of Liverpool Cancer Research Centre, Institute of Translational Medicine, The University of Liverpool, Liverpool, UK (JKF); Department of Genetic Epidemiology, University Medical Centre Göttingen, Göttingen, Germany (HB); DKFZ-German Cancer Research Center and Translatio

Abstract

BACKGROUND:

Genome-wide association studies have identified hundreds of genetic variants associated with specific cancers. A few of these risk regions have been associated with more than one cancer site; however, a systematic evaluation of the associations between risk variants for other cancers and lung cancer risk has yet to be performed.

METHODS:

We included 18023 patients with lung cancer and 60543 control subjects from two consortia, Population Architecture using Genomics and Epidemiology (PAGE) and Transdisciplinary Research in Cancer of the Lung (TRICL). We examined 165 single-nucleotide polymorphisms (SNPs) that were previously associated with at least one of 16 non-lung cancer sites. Study-specific logistic regression results underwent meta-analysis, and associations were also examined by race/ethnicity, histological cell type, sex, and smoking status. A Bonferroni-corrected P value of 2.5×10(-5) was used to assign statistical significance.

RESULTS:

The breast cancer SNP LSP1 rs3817198 was associated with an increased risk of lung cancer (odds ratio [OR] = 1.10; 95% confidence interval [CI] = 1.05 to 1.14; P = 2.8×10(-6)). This association was strongest for women with adenocarcinoma (P = 1.2×10(-4)) and not statistically significant in men (P = .14) with this cell type (P het by sex = .10). Two glioma risk variants, TERT rs2853676 and CDKN2BAS1 rs4977756, which are located in regions previously associated with lung cancer, were associated with increased risk of adenocarcinoma (OR = 1.16; 95% CI = 1.10 to 1.22; P = 1.1×10(-8)) and squamous cell carcinoma (OR = 1.13; CI = 1.07 to 1.19; P = 2.5×10(-5)), respectively.

CONCLUSIONS:

Our findings demonstrate a novel pleiotropic association between the breast cancer LSP1 risk region marked by variant rs3817198 and lung cancer risk.

PMID:
24681604
[PubMed - indexed for MEDLINE]
PMCID:
PMC3982896
Free PMC Article

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