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

TitlePleiotropic associations of risk variants identified for other cancers with lung cancer risk: the PAGE and TRICL consortia.
Publication TypeJournal Article
Year of Publication2014
AuthorsS Park L, Fesinmeyer MD, Timofeeva M, Caberto CP, Kocarnik JM, Han Y, Love S-A, Young A, Dumitrescu L, Lin Y, Goodloe R, Wilkens LR, Hindorff L, Fowke JH, Carty C, Buyske S, Schumacher FR, Butler A, Dilks H, Deelman E, Cote ML, Chen W, Pande M, Christiani DC, Field JK, Bickebller H, Risch A, Heinrich J, Brennan P, Wang Y, Eisen T, Houlston RS, Thun M, Albanes D, Caporaso N, Peters U, North KE, Heiss G, Crawford DC, Bush WS, Haiman CA, Landi M T, Hung RJ, Kooperberg C, Amos CI, Le Marchand L
Secondary AuthorsCheng I
JournalJ Natl Cancer Inst
Volume106
Issue4
Paginationdju061
Date Published2014 Apr
ISSN1460-2105
KeywordsAdenocarcinoma, Adult, Aged, Breast Neoplasms, Cyclin-Dependent Kinase Inhibitor p15, Female, Genome-Wide Association Study, Humans, Interdisciplinary Communication, Logistic Models, Lung Neoplasms, Male, Microfilament Proteins, Middle Aged, Odds Ratio, Polymorphism, Single Nucleotide, Proto-Oncogene Proteins, Risk Factors, Sex Factors, Smoking, Telomerase
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.

DOI10.1093/jnci/dju061
Alternate JournalJ Natl Cancer Inst
PubMed ID24681604
PubMed Central IDPMC3982896
Grant ListP30 CA016672 / CA / NCI NIH HHS / United States
T32 GM080178 / GM / NIGMS NIH HHS / United States
U01 HG004790 / HG / NHGRI NIH HHS / United States
U01 HG007376 / HG / NHGRI NIH HHS / United States
U01HG004803 / HG / NHGRI NIH HHS / United States
U01HG004802 / HG / NHGRI NIH HHS / United States
P30 CA023108 / CA / NCI NIH HHS / United States
K07 CA160753 / CA / NCI NIH HHS / United States
T32 CA009168 / CA / NCI NIH HHS / United States
U01HG004798 / HG / NHGRI NIH HHS / United States
U01HG004801 / HG / NHGRI NIH HHS / United States
U01HG004790 / HG / NHGRI NIH HHS / United States
T32 HL007055 / HL / NHLBI NIH HHS / United States
P30 CA071789 / CA / NCI NIH HHS / United States