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

S. Lani Park; Megan D. Fesinmeyer; Maria Timofeeva; Christian P. Caberto; Jonathan M. Kocarnik; Younghun Han; Shelly Ann Love; Alicia Young; Logan Dumitrescu; Yi Lin; Robert Goodloe; Lynne R. Wilkens; Lucia Hindorff; Jay H. Fowke; Cara Carty; Steven Buyske; Frederick R. Schumacher; Anne Butler; Holli Dilks; Ewa Deelman; Michele L. Cote; Wei Chen; Mala Pande; David C. Christiani; John K. Field; Heike Bickebller; Angela Risch; Joachim Heinrich; Paul Brennan; Yufei Wang; Timothy Eisen; Richard S. Houlston; Michael Thun; Demetrius Albanes; Neil Caporaso; Ulrike Peters; Kari E. North; Gerardo Heiss; Dana C. Crawford; William S. Bush; Christopher A. Haiman; Maria Teresa Landi; Rayjean J. Hung; Charles Kooperberg; Christopher I. Amos; Loïc Le Marchand; Iona Cheng

doi:10.1093/jnci/dju061

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

S. Lani Park, Megan D. Fesinmeyer, Maria Timofeeva, Christian P. Caberto, Jonathan M. Kocarnik, Younghun Han, Shelly Ann Love, Alicia Young, Logan Dumitrescu, Yi Lin, Robert Goodloe, Lynne R. Wilkens, Lucia Hindorff, Jay H. Fowke, Cara Carty, Steven Buyske, Frederick R. Schumacher, Anne Butler, Holli Dilks, Ewa DeelmanMichele L. Cote, Wei Chen, Mala Pande, David C. Christiani, John K. Field, Heike Bickebller, Angela Risch, Joachim Heinrich, Paul Brennan, Yufei Wang, Timothy Eisen, Richard S. Houlston, Michael Thun, Demetrius Albanes, Neil Caporaso, Ulrike Peters, Kari E. North, Gerardo Heiss, Dana C. Crawford, William S. Bush, Christopher A. Haiman, Maria Teresa Landi, Rayjean J. Hung, Charles Kooperberg, Christopher I. Amos, Loïc Le Marchand, Iona Cheng

Research output: Contribution to journal › Article › peer-review

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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. ResultsThe 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.

Original language	English (US)
Journal	Journal of the National Cancer Institute
Volume	106
Issue number	4
DOIs	https://doi.org/10.1093/jnci/dju061
State	Published - Apr 2014

ASJC Scopus subject areas

Oncology
Cancer Research

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Park, S. L., Fesinmeyer, M. D., Timofeeva, M., Caberto, C. P., Kocarnik, J. M., Han, Y., Love, S. A., Young, A., Dumitrescu, L., Lin, Y., Goodloe, R., Wilkens, L. R., Hindorff, L., Fowke, J. H., Carty, C., Buyske, S., Schumacher, F. R., Butler, A., Dilks, H., ... Cheng, I. (2014). Pleiotropic associations of risk variants identified for other cancers with lung cancer risk: The PAGE and TRICL consortia. Journal of the National Cancer Institute, 106(4). https://doi.org/10.1093/jnci/dju061

Park, SL, Fesinmeyer, MD, Timofeeva, M, Caberto, CP, Kocarnik, JM, Han, Y, Love, SA, 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, MT, Hung, RJ, Kooperberg, C, Amos, CI, Le Marchand, L & Cheng, I 2014, 'Pleiotropic associations of risk variants identified for other cancers with lung cancer risk: The PAGE and TRICL consortia', Journal of the National Cancer Institute, vol. 106, no. 4. https://doi.org/10.1093/jnci/dju061

@article{859ca05d966a4115ac5c36d0f93f34c6,

title = "Pleiotropic associations of risk variants identified for other cancers with lung cancer risk: The PAGE and TRICL consortia",

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. ResultsThe 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 (Phet 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.",

author = "Park, {S. Lani} and Fesinmeyer, {Megan D.} and Maria Timofeeva and Caberto, {Christian P.} and Kocarnik, {Jonathan M.} and Younghun Han and Love, {Shelly Ann} and Alicia Young and Logan Dumitrescu and Yi Lin and Robert Goodloe and Wilkens, {Lynne R.} and Lucia Hindorff and Fowke, {Jay H.} and Cara Carty and Steven Buyske and Schumacher, {Frederick R.} and Anne Butler and Holli Dilks and Ewa Deelman and Cote, {Michele L.} and Wei Chen and Mala Pande and Christiani, {David C.} and Field, {John K.} and Heike Bickebller and Angela Risch and Joachim Heinrich and Paul Brennan and Yufei Wang and Timothy Eisen and Houlston, {Richard S.} and Michael Thun and Demetrius Albanes and Neil Caporaso and Ulrike Peters and North, {Kari E.} and Gerardo Heiss and Crawford, {Dana C.} and Bush, {William S.} and Haiman, {Christopher A.} and Landi, {Maria Teresa} and Hung, {Rayjean J.} and Charles Kooperberg and Amos, {Christopher I.} and {Le Marchand}, Lo{\"i}c and Iona Cheng",

year = "2014",

month = apr,

doi = "10.1093/jnci/dju061",

language = "English (US)",

volume = "106",

journal = "Journal of the National Cancer Institute",

issn = "0027-8874",

publisher = "Oxford University Press",

number = "4",

}

TY - JOUR

T1 - Pleiotropic associations of risk variants identified for other cancers with lung cancer risk

T2 - The PAGE and TRICL consortia

AU - Park, S. Lani

AU - Fesinmeyer, Megan D.

AU - Timofeeva, Maria

AU - Caberto, Christian P.

AU - Kocarnik, Jonathan M.

AU - Han, Younghun

AU - Love, Shelly Ann

AU - Young, Alicia

AU - Dumitrescu, Logan

AU - Lin, Yi

AU - Goodloe, Robert

AU - Wilkens, Lynne R.

AU - Hindorff, Lucia

AU - Fowke, Jay H.

AU - Carty, Cara

AU - Buyske, Steven

AU - Schumacher, Frederick R.

AU - Butler, Anne

AU - Dilks, Holli

AU - Deelman, Ewa

AU - Cote, Michele L.

AU - Chen, Wei

AU - Pande, Mala

AU - Christiani, David C.

AU - Field, John K.

AU - Bickebller, Heike

AU - Risch, Angela

AU - Heinrich, Joachim

AU - Brennan, Paul

AU - Wang, Yufei

AU - Eisen, Timothy

AU - Houlston, Richard S.

AU - Thun, Michael

AU - Albanes, Demetrius

AU - Caporaso, Neil

AU - Peters, Ulrike

AU - North, Kari E.

AU - Heiss, Gerardo

AU - Crawford, Dana C.

AU - Bush, William S.

AU - Haiman, Christopher A.

AU - Landi, Maria Teresa

AU - Hung, Rayjean J.

AU - Kooperberg, Charles

AU - Amos, Christopher I.

AU - Le Marchand, Loïc

AU - Cheng, Iona

PY - 2014/4

Y1 - 2014/4

N2 - 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. ResultsThe 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 (Phet 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.

AB - 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. ResultsThe 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 (Phet 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.

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UR - http://www.scopus.com/inward/citedby.url?scp=84898899793&partnerID=8YFLogxK

U2 - 10.1093/jnci/dju061

DO - 10.1093/jnci/dju061

M3 - Article

C2 - 24681604

AN - SCOPUS:84898899793

SN - 0027-8874

VL - 106

JO - Journal of the National Cancer Institute

JF - Journal of the National Cancer Institute

IS - 4

ER -

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

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ASJC Scopus subject areas

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