Association of Single Nucleotide Polymorphisms in PIM-1 Gene with the Risk of Korean Lung Cancer
2
조회
0
다운로드
2
인용
0
참고문헌
키워드
초록
Purpose: The expression of the PIM-1 gene, which is a proto-oncogene that encodes a serine/threonine kinase, is associated with multiple cellular functions such as proliferation, differentiation, apoptosis and tumorigenesis. In particular, several studies have reported that the PIM-1 gene is associated with the development of lymphoma, leukemia and prostate cancer. Therefore, this study was conducted to evaluate the association between the single nucleotide polymorphisms in the PIM-1 gene and the risk of lung cancer occurrence in the Korean population. Materials and Methods: To evaluate the role of the PIM-1 gene in the development of lung cancer, the genotypes of the PIM-1 gene were determined in 408 lung cancer patients and 410 normal subjects. Results: We found that the T-C-T-C haplotypes of the PIM-1 gene (−1196 T>C, IVS4 +55 T>C, IVS4 +1416 T>A and +3684 C>A) were associated with an increased risk of lung cancer [adjusted odds ratio (aOR): 3.98; 95% CI: 1.24∼12.75, p-value: 0.020]. In particular, these haplotypes showed an increased risk of lung cancer in males (aOR: 5.67; 95% CI: 1.32∼24.30, p-value: 0.019) and smokers (aOR: 7.82; 95% CI: 1.75∼34.98, p-value: 0.007). Conclusions: The present results suggest that the T-C-T-C haplotype of the PIM-1 gene could influence the risk of developing smoking-related lung cancer in the Korean population. Additional functional studies with an larger sample sized analysis are warranted to reconfirm our findings.
Abstract
Purpose: The expression of the PIM-1 gene, which is a proto-oncogene that encodes a serine/threonine kinase, is associated with multiple cellular functions such as proliferation, differentiation, apoptosis and tumorigenesis. In particular, several studies have reported that the PIM-1 gene is associated with the development of lymphoma, leukemia and prostate cancer. Therefore, this study was conducted to evaluate the association between the single nucleotide polymorphisms in the PIM-1 gene and the risk of lung cancer occurrence in the Korean population. Materials and Methods: To evaluate the role of the PIM-1 gene in the development of lung cancer, the genotypes of the PIM-1 gene were determined in 408 lung cancer patients and 410 normal subjects. Results: We found that the T-C-T-C haplotypes of the PIM-1 gene (−1196 T>C, IVS4 +55 T>C, IVS4 +1416 T>A and +3684 C>A) were associated with an increased risk of lung cancer [adjusted odds ratio (aOR): 3.98; 95% CI: 1.24∼12.75, p-value: 0.020]. In particular, these haplotypes showed an increased risk of lung cancer in males (aOR: 5.67; 95% CI: 1.32∼24.30, p-value: 0.019) and smokers (aOR: 7.82; 95% CI: 1.75∼34.98, p-value: 0.007). Conclusions: The present results suggest that the T-C-T-C haplotype of the PIM-1 gene could influence the risk of developing smoking-related lung cancer in the Korean population. Additional functional studies with an larger sample sized analysis are warranted to reconfirm our findings.
참고문헌 (25)
- Ionov Y., "PIM-1 protein kinase is nuclear in Burkitt's lymphoma:nuclear localization is necessary for its biologic effects", Anticancer Res, 23, pp.167~78 (2003)
- Pasqualucci L., "Hypermutation of multipleproto-oncogenes in B-cell diffuse large-cell lymphomas", Nature, 412, pp.341~6 (2001)
- Xu Y., "Overexpression of PIM-1 is a potential biomarker in prostatecarcinoma", J Surg Oncol, 92, pp.326~30 (2005)
- Oh Y., "Enzastaurin, an oral serine", threonine kinase inhibitor, assecond- or third-line therapy of non-small-cell lung cancer, 2008, pp.26, 1135~41
- Shepherd FA, "Erlotinib in previously treated nonsmall-cell lung cancer", N Engl J Med, 353, pp.123~32 (2005)
- Hai-Rim Shin, "National Cancer Incidence for the Year 2002 in Korea", Cancer Research and Treatment, 39(4), pp.139~149 (2007), 대한암학회
- Parkin DM, "Global cancer statistics,2002", CA Cancer J Clin, 55, pp.74~108 (2005)
- Brambilla E., "The new World Health Organization classification of lungtumours", Eur Respir J, 18, pp.1059~68 (2001)
- Matsuzaki H., "Parallel genotyping of over 10,000 SNPs using a one-primerassay on a high-density oligonucleotide array", Genome Res, 14, pp.414~25 (2004)
- Kruglyak L., "is the spice of life", NatGenet, 27, pp.234~6 (2001)
- Barrett JC, "Haploview: analysis andvisualization of LD and haplotype maps", Bioinformatics, 21, pp.263~5 (2005)
- Khuder SA, "Effect of cigarette smoking on major histologicaltypes of lung cancer: a meta-analysis", Lung Cancer, 31, pp.139~48 (2001)
- Belinsky SA, "Aberrant promoter methylationin bronchial epithelium and sputum from current and formersmokers", Cancer Res, 62, pp.2370~7 (2002)
- Kim DH, "Hypermethylation of RASSF1A promoter is associated withthe age at starting smoking and a poor prognosis in primarynon-small cell lung cancer", Cancer Res, 63, pp.3743~6 (2003)
- Agathanggelou A., "Methylation associated inactivationof RASSF1A from region 3p21.3 in lung, breast and ovariantumours", Oncogene, 20, pp.1509~18 (2001)
- Shields PG, "Cancer risk and low-penetrance susceptibilitygenes in gene-environment interactions", J Clin Oncol, 18, pp.2309~15 (2000)
- Sung JS, "Putative association of the single nucleotide polymorphismsin RASSF1A promoter with Korean lung cancer", LungCancer, 61, pp.301~8 (2008)
- Bachmann M., "The serine", threonine kinase PIM-1, 2005, pp.37, 726~30
- Wang Z., "PIM-1: a serine", threonine kinase with a rolein cell survival, proliferation, differentiation and tumorigenesis, 2001, pp.2, 167~79
- Mikkers H., "Mice deficient for all PIM kinases displayreduced body size and impaired responses to hematopoieticgrowth factors", Mol Cell Biol, 24, pp.6104~15 (2004)
- Cuypers HT, "Murine leukemia virus-induced T-cell lymphomagenesis:integration of proviruses in a distinct chromosomalregion", Cell, 37, pp.141~50 (1984)
- Cohen AM, "Increased expression of the hPim-2 genein human chronic lymphocytic leukemia and non-Hodgkin lymphoma", Leuk Lymphoma, 45, pp.951~5 (2004)
- Fujii C., "Aberrant expression of serine", threonine kinasePim-3 in hepatocellular carcinoma development and its role inthe proliferation of human hepatoma cell lines, 2005, pp.114, 209~18
- Herman JG, "Gene silencing in cancer in associationwith promoter hypermethylation", N Engl J Med, 349, pp.2042~54 (2003)
- Thomas RK, "Genomic approaches tolung cancer", Clin Cancer Res, 12, pp.4384s~91s (2006)
