Association Analysis of Driver Gene-Related Genetic Variants Identified Novel Lung Cancer Susceptibility Loci with 20,871 Lung Cancer Cases and 15,971 Controls

Research output: Contribution to journalJournal articlepeer-review

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Association Analysis of Driver Gene-Related Genetic Variants Identified Novel Lung Cancer Susceptibility Loci with 20,871 Lung Cancer Cases and 15,971 Controls. / Wang, Yuzhuo; Gorlova, Olga Y; Gorlov, Ivan P; Zhu, Meng; Dai, Juncheng; Albanes, Demetrius; Lam, Stephen; Tardon, Adonina; Chen, Chu; Goodman, Gary E; Bojesen, Stig E; Landi, Maria Teresa; Johansson, Mattias; Risch, Angela; Wichmann, Heunz-Erich; Bickeboller, Heike; Christiani, David C; Rennert, Gad; Arnold, Susanne M; Brennan, Paul; Field, John K; Shete, Sanjay; Le Marchand, Loïc; Melander, Olle; Brunnstrom, Hans; Liu, Geoffrey; Hung, Rayjean J; Andrew, Angeline S; Kiemeney, Lambertus A; Zienolddiny, Shanbeh; Grankvist, Kjell; Johansson, Mikael; Caporaso, Neil E; Woll, Penella J; Lazarus, Philip; Schabath, Matthew B; Aldrich, Melinda C; Stevens, Victoria L; Ma, Hongxia; Jin, Guangfu; Hu, Zhibin; Amos, Christopher I; Shen, Hongbing.

In: Cancer Epidemiology, Biomarkers & Prevention, Vol. 29, No. 7, 2020, p. 1423-1429.

Research output: Contribution to journalJournal articlepeer-review

Harvard

Wang, Y, Gorlova, OY, Gorlov, IP, Zhu, M, Dai, J, Albanes, D, Lam, S, Tardon, A, Chen, C, Goodman, GE, Bojesen, SE, Landi, MT, Johansson, M, Risch, A, Wichmann, H-E, Bickeboller, H, Christiani, DC, Rennert, G, Arnold, SM, Brennan, P, Field, JK, Shete, S, Le Marchand, L, Melander, O, Brunnstrom, H, Liu, G, Hung, RJ, Andrew, AS, Kiemeney, LA, Zienolddiny, S, Grankvist, K, Johansson, M, Caporaso, NE, Woll, PJ, Lazarus, P, Schabath, MB, Aldrich, MC, Stevens, VL, Ma, H, Jin, G, Hu, Z, Amos, CI & Shen, H 2020, 'Association Analysis of Driver Gene-Related Genetic Variants Identified Novel Lung Cancer Susceptibility Loci with 20,871 Lung Cancer Cases and 15,971 Controls', Cancer Epidemiology, Biomarkers & Prevention, vol. 29, no. 7, pp. 1423-1429. https://doi.org/10.1158/1055-9965.EPI-19-1085

APA

Wang, Y., Gorlova, O. Y., Gorlov, I. P., Zhu, M., Dai, J., Albanes, D., Lam, S., Tardon, A., Chen, C., Goodman, G. E., Bojesen, S. E., Landi, M. T., Johansson, M., Risch, A., Wichmann, H-E., Bickeboller, H., Christiani, D. C., Rennert, G., Arnold, S. M., ... Shen, H. (2020). Association Analysis of Driver Gene-Related Genetic Variants Identified Novel Lung Cancer Susceptibility Loci with 20,871 Lung Cancer Cases and 15,971 Controls. Cancer Epidemiology, Biomarkers & Prevention, 29(7), 1423-1429. https://doi.org/10.1158/1055-9965.EPI-19-1085

Vancouver

Wang Y, Gorlova OY, Gorlov IP, Zhu M, Dai J, Albanes D et al. Association Analysis of Driver Gene-Related Genetic Variants Identified Novel Lung Cancer Susceptibility Loci with 20,871 Lung Cancer Cases and 15,971 Controls. Cancer Epidemiology, Biomarkers & Prevention. 2020;29(7):1423-1429. https://doi.org/10.1158/1055-9965.EPI-19-1085

Author

Wang, Yuzhuo ; Gorlova, Olga Y ; Gorlov, Ivan P ; Zhu, Meng ; Dai, Juncheng ; Albanes, Demetrius ; Lam, Stephen ; Tardon, Adonina ; Chen, Chu ; Goodman, Gary E ; Bojesen, Stig E ; Landi, Maria Teresa ; Johansson, Mattias ; Risch, Angela ; Wichmann, Heunz-Erich ; Bickeboller, Heike ; Christiani, David C ; Rennert, Gad ; Arnold, Susanne M ; Brennan, Paul ; Field, John K ; Shete, Sanjay ; Le Marchand, Loïc ; Melander, Olle ; Brunnstrom, Hans ; Liu, Geoffrey ; Hung, Rayjean J ; Andrew, Angeline S ; Kiemeney, Lambertus A ; Zienolddiny, Shanbeh ; Grankvist, Kjell ; Johansson, Mikael ; Caporaso, Neil E ; Woll, Penella J ; Lazarus, Philip ; Schabath, Matthew B ; Aldrich, Melinda C ; Stevens, Victoria L ; Ma, Hongxia ; Jin, Guangfu ; Hu, Zhibin ; Amos, Christopher I ; Shen, Hongbing. / Association Analysis of Driver Gene-Related Genetic Variants Identified Novel Lung Cancer Susceptibility Loci with 20,871 Lung Cancer Cases and 15,971 Controls. In: Cancer Epidemiology, Biomarkers & Prevention. 2020 ; Vol. 29, No. 7. pp. 1423-1429.

Bibtex

@article{7af7fce7099c4179aad5ea57e7b69422,
title = "Association Analysis of Driver Gene-Related Genetic Variants Identified Novel Lung Cancer Susceptibility Loci with 20,871 Lung Cancer Cases and 15,971 Controls",
abstract = "BACKGROUND: A substantial proportion of cancer driver genes (CDG) are also cancer predisposition genes. However, the associations between genetic variants in lung CDGs and the susceptibility to lung cancer have rarely been investigated.METHODS: We selected expression-related single-nucleotide polymorphisms (eSNP) and nonsynonymous variants of lung CDGs, and tested their associations with lung cancer risk in two large-scale genome-wide association studies (20,871 cases and 15,971 controls of European descent). Conditional and joint association analysis was performed to identify independent risk variants. The associations of independent risk variants with somatic alterations in lung CDGs or recurrently altered pathways were investigated using data from The Cancer Genome Atlas (TCGA) project.RESULTS: We identified seven independent SNPs in five lung CDGs that were consistently associated with lung cancer risk in discovery (P < 0.001) and validation (P < 0.05) stages. Among these loci, rs78062588 in TPM3 (1q21.3) was a new lung cancer susceptibility locus (OR = 0.86, P = 1.65 × 10-6). Subgroup analysis by histologic types further identified nine lung CDGs. Analysis of somatic alterations found that in lung adenocarcinomas, rs78062588[C] allele (TPM3 in 1q21.3) was associated with elevated somatic copy number of TPM3 (OR = 1.16, P = 0.02). In lung adenocarcinomas, rs1611182 (HLA-A in 6p22.1) was associated with truncation mutations of the transcriptional misregulation in cancer pathway (OR = 0.66, P = 1.76 × 10-3).CONCLUSIONS: Genetic variants can regulate functions of lung CDGs and influence lung cancer susceptibility.IMPACT: Our findings might help unravel biological mechanisms underlying lung cancer susceptibility.",
author = "Yuzhuo Wang and Gorlova, {Olga Y} and Gorlov, {Ivan P} and Meng Zhu and Juncheng Dai and Demetrius Albanes and Stephen Lam and Adonina Tardon and Chu Chen and Goodman, {Gary E} and Bojesen, {Stig E} and Landi, {Maria Teresa} and Mattias Johansson and Angela Risch and Heunz-Erich Wichmann and Heike Bickeboller and Christiani, {David C} and Gad Rennert and Arnold, {Susanne M} and Paul Brennan and Field, {John K} and Sanjay Shete and {Le Marchand}, Lo{\"i}c and Olle Melander and Hans Brunnstrom and Geoffrey Liu and Hung, {Rayjean J} and Andrew, {Angeline S} and Kiemeney, {Lambertus A} and Shanbeh Zienolddiny and Kjell Grankvist and Mikael Johansson and Caporaso, {Neil E} and Woll, {Penella J} and Philip Lazarus and Schabath, {Matthew B} and Aldrich, {Melinda C} and Stevens, {Victoria L} and Hongxia Ma and Guangfu Jin and Zhibin Hu and Amos, {Christopher I} and Hongbing Shen",
note = "{\textcopyright}2020 American Association for Cancer Research.",
year = "2020",
doi = "10.1158/1055-9965.EPI-19-1085",
language = "English",
volume = "29",
pages = "1423--1429",
journal = "Cancer Epidemiology, Biomarkers & Prevention",
issn = "1055-9965",
publisher = "American Association for Cancer Research (A A C R)",
number = "7",

}

RIS

TY - JOUR

T1 - Association Analysis of Driver Gene-Related Genetic Variants Identified Novel Lung Cancer Susceptibility Loci with 20,871 Lung Cancer Cases and 15,971 Controls

AU - Wang, Yuzhuo

AU - Gorlova, Olga Y

AU - Gorlov, Ivan P

AU - Zhu, Meng

AU - Dai, Juncheng

AU - Albanes, Demetrius

AU - Lam, Stephen

AU - Tardon, Adonina

AU - Chen, Chu

AU - Goodman, Gary E

AU - Bojesen, Stig E

AU - Landi, Maria Teresa

AU - Johansson, Mattias

AU - Risch, Angela

AU - Wichmann, Heunz-Erich

AU - Bickeboller, Heike

AU - Christiani, David C

AU - Rennert, Gad

AU - Arnold, Susanne M

AU - Brennan, Paul

AU - Field, John K

AU - Shete, Sanjay

AU - Le Marchand, Loïc

AU - Melander, Olle

AU - Brunnstrom, Hans

AU - Liu, Geoffrey

AU - Hung, Rayjean J

AU - Andrew, Angeline S

AU - Kiemeney, Lambertus A

AU - Zienolddiny, Shanbeh

AU - Grankvist, Kjell

AU - Johansson, Mikael

AU - Caporaso, Neil E

AU - Woll, Penella J

AU - Lazarus, Philip

AU - Schabath, Matthew B

AU - Aldrich, Melinda C

AU - Stevens, Victoria L

AU - Ma, Hongxia

AU - Jin, Guangfu

AU - Hu, Zhibin

AU - Amos, Christopher I

AU - Shen, Hongbing

N1 - ©2020 American Association for Cancer Research.

PY - 2020

Y1 - 2020

N2 - BACKGROUND: A substantial proportion of cancer driver genes (CDG) are also cancer predisposition genes. However, the associations between genetic variants in lung CDGs and the susceptibility to lung cancer have rarely been investigated.METHODS: We selected expression-related single-nucleotide polymorphisms (eSNP) and nonsynonymous variants of lung CDGs, and tested their associations with lung cancer risk in two large-scale genome-wide association studies (20,871 cases and 15,971 controls of European descent). Conditional and joint association analysis was performed to identify independent risk variants. The associations of independent risk variants with somatic alterations in lung CDGs or recurrently altered pathways were investigated using data from The Cancer Genome Atlas (TCGA) project.RESULTS: We identified seven independent SNPs in five lung CDGs that were consistently associated with lung cancer risk in discovery (P < 0.001) and validation (P < 0.05) stages. Among these loci, rs78062588 in TPM3 (1q21.3) was a new lung cancer susceptibility locus (OR = 0.86, P = 1.65 × 10-6). Subgroup analysis by histologic types further identified nine lung CDGs. Analysis of somatic alterations found that in lung adenocarcinomas, rs78062588[C] allele (TPM3 in 1q21.3) was associated with elevated somatic copy number of TPM3 (OR = 1.16, P = 0.02). In lung adenocarcinomas, rs1611182 (HLA-A in 6p22.1) was associated with truncation mutations of the transcriptional misregulation in cancer pathway (OR = 0.66, P = 1.76 × 10-3).CONCLUSIONS: Genetic variants can regulate functions of lung CDGs and influence lung cancer susceptibility.IMPACT: Our findings might help unravel biological mechanisms underlying lung cancer susceptibility.

AB - BACKGROUND: A substantial proportion of cancer driver genes (CDG) are also cancer predisposition genes. However, the associations between genetic variants in lung CDGs and the susceptibility to lung cancer have rarely been investigated.METHODS: We selected expression-related single-nucleotide polymorphisms (eSNP) and nonsynonymous variants of lung CDGs, and tested their associations with lung cancer risk in two large-scale genome-wide association studies (20,871 cases and 15,971 controls of European descent). Conditional and joint association analysis was performed to identify independent risk variants. The associations of independent risk variants with somatic alterations in lung CDGs or recurrently altered pathways were investigated using data from The Cancer Genome Atlas (TCGA) project.RESULTS: We identified seven independent SNPs in five lung CDGs that were consistently associated with lung cancer risk in discovery (P < 0.001) and validation (P < 0.05) stages. Among these loci, rs78062588 in TPM3 (1q21.3) was a new lung cancer susceptibility locus (OR = 0.86, P = 1.65 × 10-6). Subgroup analysis by histologic types further identified nine lung CDGs. Analysis of somatic alterations found that in lung adenocarcinomas, rs78062588[C] allele (TPM3 in 1q21.3) was associated with elevated somatic copy number of TPM3 (OR = 1.16, P = 0.02). In lung adenocarcinomas, rs1611182 (HLA-A in 6p22.1) was associated with truncation mutations of the transcriptional misregulation in cancer pathway (OR = 0.66, P = 1.76 × 10-3).CONCLUSIONS: Genetic variants can regulate functions of lung CDGs and influence lung cancer susceptibility.IMPACT: Our findings might help unravel biological mechanisms underlying lung cancer susceptibility.

U2 - 10.1158/1055-9965.EPI-19-1085

DO - 10.1158/1055-9965.EPI-19-1085

M3 - Journal article

C2 - 32277007

VL - 29

SP - 1423

EP - 1429

JO - Cancer Epidemiology, Biomarkers & Prevention

JF - Cancer Epidemiology, Biomarkers & Prevention

SN - 1055-9965

IS - 7

ER -

ID: 261177429