J Korean Med Sci.  2013 Jun;28(6):840-847. 10.3346/jkms.2013.28.6.840.

Genome-Wide Association Study of Lung Cancer in Korean Non-Smoking Women

• Kim JH
• Park K
• Yim SH
• Choi JE
• Sung JS
• Park JY
• Choi YY
• Jeon HS
• Park JY
• Yoon HK
• Kim YH
• Yoo BS
• Kim YT
• Hu HJ
• Chung YJ
• Kim H
• Sung SW
• Hong YC

• KMID: 2158030
• DOI: http://doi.org/10.3346/jkms.2013.28.6.840

Abstract

Lung cancer in never-smokers ranks as the seventh most common cause of cancer death worldwide, and the incidence of lung cancer in non-smoking Korean women appears to be steadily increasing. To identify the effect of genetic polymorphisms on lung cancer risk in non-smoking Korean women, we conducted a genome-wide association study of Korean female non-smokers with lung cancer. We analyzed 440,794 genotype data of 285 cases and 1,455 controls, and nineteen SNPs were associated with lung cancer development (P < 0.001). For external validation, nineteen SNPs were replicated in another sample set composed of 293 cases and 495 controls, and only rs10187911 on 2p16.3 was significantly associated with lung cancer development (dominant model, OR of TG or GG, 1.58, P = 0.025). We confirmed this SNP again in another replication set composed of 546 cases and 744 controls (recessive model, OR of GG, 1.32, P = 0.027). OR and P value in combined set were 1.37 and < 0.001 in additive model, 1.51 and < 0.001 in dominant model, and 1.54 and < 0.001 in recessive model. The effect of this SNP was found to be consistent only in adenocarcinoma patients (1.36 and < 0.001 in additive model, 1.49 and < 0.001 in dominant model, and 1.54 and < 0.001 in recessive model). Furthermore, after imputation with HapMap data, we found regional significance near rs10187911, and five SNPs showed P value less than that of rs10187911 (rs12478012, rs4377361, rs13005521, rs12475464, and rs7564130). Therefore, we concluded that a region on chromosome 2 is significantly associated with lung cancer risk in Korean non-smoking women.

Keyword

Lung Neoplasms; Genome-Wide Association Study; Non-Smoking Women

MeSH Terms

Adenocarcinoma/*genetics/pathology
Adult
Aged
Asian Continental Ancestry Group/*genetics
Cell Adhesion Molecules, Neuronal/*genetics
Chromosomes, Human, Pair 2
Female
*Genome-Wide Association Study
Genotype
Humans
Logistic Models
Lung Neoplasms/*genetics/pathology
Models, Genetic
Nerve Tissue Proteins/*genetics
Odds Ratio
Polymorphism, Single Nucleotide
Republic of Korea
Cell Adhesion Molecules, Neuronal
Nerve Tissue Proteins

Figure

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  Fig. 1 Quantile-quantile plot of P value.

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  Fig. 2 Summary of odds ratio (OR) and confidence interval (CI) by center. The number of cases, OR, and 95% CI were depicted in order in brackets.

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  Fig. 3 Regional plot surrounding rs10187911.

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