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 journal › Journal article › peer-review
Standard
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 journal › Journal article › peer-review
Harvard
APA
Vancouver
Author
Bibtex
}
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