The 18p11.22 locus is associated with never smoker non-small cell lung cancer susceptibility in Korean populations

Myung Ju Ahn, Hong Hee Won, Jeeyun Lee, Seung Tae Lee, Jong Mu Sun, Yeon Hee Park, Jin Seok Ahn, O. Jung Kwon, Hojoong Kim, Young Mog Shim, Jhingook Kim, Kwhanmien Kim, Yeul Hong Kim, Jae Yong Park, Jong Won Kim, Keunchil Park

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Abstract

The proportion of never smoker non-small cell lung cancer (NSCLC) in Asia is about 30-40%. Despite the striking demographics and high prevalence of never smoker NSCLC, the exact causes still remain undetermined. Although several genome wide association (GWA) studies were conducted to find susceptibility loci for lung cancer in never smokers, no regions were replicated except for 5p15.33, suggesting locus heterogeneity and different environmental toxic effects. To identify genetic loci associated with susceptibility of lung cancer in never smokers, we performed a GWA analysis using the Affymetrix 6.0 SNP array. For discovery GWA set, we recruited 446 never smoking Korean patients with NSCLC and 497 normal subjects. We tested association of SNPs with lung cancer susceptibility using the Cochran-Armitage trend test. For validation, 39 SNPs were selected from the top 50 SNPs and five additional SNPs were selected in the DAB1 gene region which showed significant associations in the GWA analysis. The validation SNPs were genotyped in an independent sample including 434 patients and 1,000 controls. Among the 44 validation SNPs, two SNPs (rs11080466 and rs11663246) near the APCDD1, NAPG and FAM38B genes in the 18p11.22 region were replicated. P value of rs11080466 was 1.08 9 10 -6 in the combined sets (2.68 9 10 -5 in the discovery set and 2.60 9 10 -3 in the validation set) and odds ratio was 0.68 (0.58-0.79). We observed similar association for rs11663246. Our result suggests the 18p11.22 region as a novel lung cancer susceptibility locus in never smokers.

Original languageEnglish
Pages (from-to)365-372
Number of pages8
JournalHuman Genetics
Volume131
Issue number3
DOIs
Publication statusPublished - 2012 Mar 1

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Non-Small Cell Lung Carcinoma
Single Nucleotide Polymorphism
Population
Genome-Wide Association Study
Lung Neoplasms
Genetic Loci
Poisons
Genes
Smoking
Odds Ratio
Demography
Genome

ASJC Scopus subject areas

  • Genetics(clinical)
  • Genetics

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The 18p11.22 locus is associated with never smoker non-small cell lung cancer susceptibility in Korean populations. / Ahn, Myung Ju; Won, Hong Hee; Lee, Jeeyun; Lee, Seung Tae; Sun, Jong Mu; Park, Yeon Hee; Ahn, Jin Seok; Kwon, O. Jung; Kim, Hojoong; Shim, Young Mog; Kim, Jhingook; Kim, Kwhanmien; Kim, Yeul Hong; Park, Jae Yong; Kim, Jong Won; Park, Keunchil.

In: Human Genetics, Vol. 131, No. 3, 01.03.2012, p. 365-372.

Research output: Contribution to journalArticle

Ahn, MJ, Won, HH, Lee, J, Lee, ST, Sun, JM, Park, YH, Ahn, JS, Kwon, OJ, Kim, H, Shim, YM, Kim, J, Kim, K, Kim, YH, Park, JY, Kim, JW & Park, K 2012, 'The 18p11.22 locus is associated with never smoker non-small cell lung cancer susceptibility in Korean populations', Human Genetics, vol. 131, no. 3, pp. 365-372. https://doi.org/10.1007/s00439-011-1080-z
Ahn, Myung Ju ; Won, Hong Hee ; Lee, Jeeyun ; Lee, Seung Tae ; Sun, Jong Mu ; Park, Yeon Hee ; Ahn, Jin Seok ; Kwon, O. Jung ; Kim, Hojoong ; Shim, Young Mog ; Kim, Jhingook ; Kim, Kwhanmien ; Kim, Yeul Hong ; Park, Jae Yong ; Kim, Jong Won ; Park, Keunchil. / The 18p11.22 locus is associated with never smoker non-small cell lung cancer susceptibility in Korean populations. In: Human Genetics. 2012 ; Vol. 131, No. 3. pp. 365-372.
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abstract = "The proportion of never smoker non-small cell lung cancer (NSCLC) in Asia is about 30-40{\%}. Despite the striking demographics and high prevalence of never smoker NSCLC, the exact causes still remain undetermined. Although several genome wide association (GWA) studies were conducted to find susceptibility loci for lung cancer in never smokers, no regions were replicated except for 5p15.33, suggesting locus heterogeneity and different environmental toxic effects. To identify genetic loci associated with susceptibility of lung cancer in never smokers, we performed a GWA analysis using the Affymetrix 6.0 SNP array. For discovery GWA set, we recruited 446 never smoking Korean patients with NSCLC and 497 normal subjects. We tested association of SNPs with lung cancer susceptibility using the Cochran-Armitage trend test. For validation, 39 SNPs were selected from the top 50 SNPs and five additional SNPs were selected in the DAB1 gene region which showed significant associations in the GWA analysis. The validation SNPs were genotyped in an independent sample including 434 patients and 1,000 controls. Among the 44 validation SNPs, two SNPs (rs11080466 and rs11663246) near the APCDD1, NAPG and FAM38B genes in the 18p11.22 region were replicated. P value of rs11080466 was 1.08 9 10 -6 in the combined sets (2.68 9 10 -5 in the discovery set and 2.60 9 10 -3 in the validation set) and odds ratio was 0.68 (0.58-0.79). We observed similar association for rs11663246. Our result suggests the 18p11.22 region as a novel lung cancer susceptibility locus in never smokers.",
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AU - Ahn, Myung Ju

AU - Won, Hong Hee

AU - Lee, Jeeyun

AU - Lee, Seung Tae

AU - Sun, Jong Mu

AU - Park, Yeon Hee

AU - Ahn, Jin Seok

AU - Kwon, O. Jung

AU - Kim, Hojoong

AU - Shim, Young Mog

AU - Kim, Jhingook

AU - Kim, Kwhanmien

AU - Kim, Yeul Hong

AU - Park, Jae Yong

AU - Kim, Jong Won

AU - Park, Keunchil

PY - 2012/3/1

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N2 - The proportion of never smoker non-small cell lung cancer (NSCLC) in Asia is about 30-40%. Despite the striking demographics and high prevalence of never smoker NSCLC, the exact causes still remain undetermined. Although several genome wide association (GWA) studies were conducted to find susceptibility loci for lung cancer in never smokers, no regions were replicated except for 5p15.33, suggesting locus heterogeneity and different environmental toxic effects. To identify genetic loci associated with susceptibility of lung cancer in never smokers, we performed a GWA analysis using the Affymetrix 6.0 SNP array. For discovery GWA set, we recruited 446 never smoking Korean patients with NSCLC and 497 normal subjects. We tested association of SNPs with lung cancer susceptibility using the Cochran-Armitage trend test. For validation, 39 SNPs were selected from the top 50 SNPs and five additional SNPs were selected in the DAB1 gene region which showed significant associations in the GWA analysis. The validation SNPs were genotyped in an independent sample including 434 patients and 1,000 controls. Among the 44 validation SNPs, two SNPs (rs11080466 and rs11663246) near the APCDD1, NAPG and FAM38B genes in the 18p11.22 region were replicated. P value of rs11080466 was 1.08 9 10 -6 in the combined sets (2.68 9 10 -5 in the discovery set and 2.60 9 10 -3 in the validation set) and odds ratio was 0.68 (0.58-0.79). We observed similar association for rs11663246. Our result suggests the 18p11.22 region as a novel lung cancer susceptibility locus in never smokers.

AB - The proportion of never smoker non-small cell lung cancer (NSCLC) in Asia is about 30-40%. Despite the striking demographics and high prevalence of never smoker NSCLC, the exact causes still remain undetermined. Although several genome wide association (GWA) studies were conducted to find susceptibility loci for lung cancer in never smokers, no regions were replicated except for 5p15.33, suggesting locus heterogeneity and different environmental toxic effects. To identify genetic loci associated with susceptibility of lung cancer in never smokers, we performed a GWA analysis using the Affymetrix 6.0 SNP array. For discovery GWA set, we recruited 446 never smoking Korean patients with NSCLC and 497 normal subjects. We tested association of SNPs with lung cancer susceptibility using the Cochran-Armitage trend test. For validation, 39 SNPs were selected from the top 50 SNPs and five additional SNPs were selected in the DAB1 gene region which showed significant associations in the GWA analysis. The validation SNPs were genotyped in an independent sample including 434 patients and 1,000 controls. Among the 44 validation SNPs, two SNPs (rs11080466 and rs11663246) near the APCDD1, NAPG and FAM38B genes in the 18p11.22 region were replicated. P value of rs11080466 was 1.08 9 10 -6 in the combined sets (2.68 9 10 -5 in the discovery set and 2.60 9 10 -3 in the validation set) and odds ratio was 0.68 (0.58-0.79). We observed similar association for rs11663246. Our result suggests the 18p11.22 region as a novel lung cancer susceptibility locus in never smokers.

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