35 1 Journal of the Korean Society of Health Information and Health Statistics Volume 35, Number 1, 2010, pp ) 1) 2) 1) 1) Cadherin-1 (CDH1) po

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1 35 1 Journal of the Korean Society of Health Information and Health Statistics Volume 35, Number 1, 2010, pp ) 1) 2) 1) 1) Cadherin-1 (CDH1) polymorphism and the risk of colorectal cancer: A meta-analysis Abstract Purpose: Conflicting results on the association between cadherin-1 (CDH1) gene -160C>A polymorphism and risk of colorectal cancer have been reported. In order to clarify the effect of CDH1 polymorphism on the risk of colorectal cancer, we intended to perform a meta-analysis using published data. Methods: We attempted to search English literatures for all literat of possible effects of CDH-1 gene on colorectal cancer in human published prior to February We used a random effect model to perform a meta-analysis of 6 case-control studies that provided information related to the effects of CDH1 gene on colorectal cancer. Results: In a meta-analysis, a total of 13,278 participants (case: 6,603, control: 6,675) were included from selected 6 studies. From 5 studies for CDH1-160C>A (rs16260) in relation to colorectal cancer, when compared with the reference genotype, the odds for CA genotype was (0.858, 0.985; p = 0.017), whereas the odds for AA genotype was (0.704, 0.909; p = 0.001). Similarly, from 2 studies for CDH1-347G>A (rs ) in relation to colorectal cancer was (1.029, 1.722; p =0.029). Conclusion: Our findings support that CDH1-160C>A is significantly associated with colorectal cancer risk. Further studies are needed. Key words: Gene, Colorectal cancer, Cadherin-1, meta-analysis * (10526) ( ). * : / jsunha@yuhs.ac

2 2 2.1 연구논문의수집 35 1

3 CDH1-160C>A 3 Figure 1. Study flow diagram Figure 2. SNP map of the CDH1 promoter and 5' non-coding region. Locations of SNPs are indicated

4 4 2.2 분석정보의추출 2.3 통계적분석방법 35 1

5 CDH1-160C>A 5 ʈ

6 6 3.1 연구문헌의정성적메타분석 3.2 대장결장암발생에유전자다형성 -160C>A 의관련성분석 3.3 대장결장암발생에유전자다형성 -347G>A 의관련성분석 35 1

7 CDH1-160C>A 7 Table 1. Summary of general characteristic in case-control studies of CDH1 polymorphism and colorectal cancer Investigators Year Age Male (%) Ethnic group Colorectal cancer Percent of familial cases (%) Case Control Selection of cases Selection of control Nakamura et al Japanese Total NR Porter et al European Sporadic Shin et al Korean Sporadic Cattaneo et al Grunhage et al European Sporadic NR European Familial Zou et al Chinese Total NR Pittman et al Hospital patient Hospital patient Hospital patient Hospital patient Healthy controls Healthy controls Healthy controls Healthy controls Populati Population on based based controls from cases from a a cohort cohort study study Hospital patient Healthy controls Caucasian Total NSCCG NSCCG NR: not responded NSCCG: National study of Colorectal cancer genetics

8 8 Table 2. Summary of genetic characteristics in case-control studies of CDH1polymorphism and colorectal cancer Investigators, year HWE MAF (%) SNP Comparison Porter et al, 2002 Satisfied C/A CA vs CC AA vs CC Shin et al, 2004 Satisfied G/A GA vs GG Shin et al, 2004 Satisfied C/A Cattaneo et al, 2006 Grunhage et al, 2007 Satisfied C/A Satisfied C/A CA vs CC AA vs CC CA vs CC AA vs CC CA vs CC AA vs CC Zou et al, 2009 NR G/A GA vs GG Pittman et al, 2009 Satisfied C/A CA vs CC AA vs CC HWE: hardy-weinberg equilibrium MAF: minor allele frequency SNP: single nucleotide polymorphism NR: not respond 35 1

9 CDH1-160C>A 9 Figure 3. Forest plot for the association between CDH1-160C/A polymorphism and risk of colorectal cancer Figure 4. Forest plot for the association between CDH1-347G/A polymorphism and risk of colorectal cancer

10 10 Figure 5. Funnel plot of the published studies considered in the meta-analysis 35 1

11 CDH1-160C>A 11

13 CDH1-160C>A 13 [1] Jemal A, Siegel R, Ward E, et al. Cancer statistics, CA Cancer J Clin 2006;56: [2] Fengju S, Guanglin W, Kexin C. Incidence of colon cancer in Tianjin, China, Asia Pac J Public Health 2005;17:22-5. [3] Lichtenstein P, Holm NV, Verkasalo PK, et al. Environmental and heritable factors in the causation of cancer-analyses of cohorts of twins from Sweden, Denmark, and Finland. N Engl J Med 2000;343: [4] Aaltonen L, Johns L, Jarvinen H, et al. Explaining the familial colorectal cancer risk associated with mismatch repair (MMR)-deficient and MMR-stable tumors. Clin Cancer Res 2007;13: [5] Zanke BW, Greenwood Cm, Rangrej J, et al. Genome-wide association scan identifies a colorectal cancer susceptibility locus on chromosome 8q24. Nat Genet : [6] Tomlinson I, Webb E, Carvajal-Carmona L, et al. A genome-wide association scan of tag SNPs identifies a susceptibility variant for colorectal cancer at 8q Nat Genet 2007;39: [7] Tomlinson IP, Webb E, Carvajal-Carmona L, et al. A genome-wide association study identifies colorectal cancer susceptibility loci on chromosomes 10p14 and 8q23.3. Nat Genet 2008;40: [8] Tenesa A, Farrington SM, Prendergast JG, et al. Genome-wide association scan identifies a colorectal cancer susceptibility locus on 11q23 and replicates risk olci at 8q24 and 18q21. Nat Genet 2008;40: [9] Jaeger E, Webb E, Howarth K, et al. Common genetic variants at the CRAC1 (HMPS) locus on chromosome 15q13.3 influence colorectal cancer risk. Nat Genet 2008;40:26-8. [10] Broderick P, Carvajal-Carmona L, Pittman AM, et al. A genome-wide association study show that common alleles of SMAD7 influence colorectal cancer risk. Nat Genet 2007;39: [11] Gumbiner BM. Regulationof cadherin-mediated adhesion in morphogenesis. Nat Rev Mol Cell Biol 2005;6: [12] Koriyama C, Akiba S, Itoh T, et al. E-cadherin and betacatenin expression in Epstein-Barr virus-associated gastric cardinoma and their prognostic significance. World J Gastroenterol 2007;13: [13] Chen HC, Chu RY, Hsu PN, et al. Loss of E-cadherin expression correlates with poor differentiation and invasion into adjacent organs in gastric adenocarcinomas. Cancer Lett 2003;201: [14] Pittman AM, Twiss P, Broderick P, et al. The CDH1-160C>A polymorphism

14 14 is a risk factor for colorectal cancer. Int J Cancer 2009;125: [15] Grunhage F, Jungck M, Lamberti C, et al. Association of familial colorectal cancer with variants in the E-cadherin (CDH1) and cyclin D1 (CCND1) genes. Int J Colorectal Dis 2008;32: [16] Porter TR, Richards FM, Houlston RS, et al. Contribution of cyclin d1 (CCND1) and E-cadherin (CDH1) polymorphisms to familial and sporadic colorectal cancer. Oncogene 2002;21: [17] Shin Y, Kim IJ, Kang HC, et al. A functional polymorphism (-347GGA) in the E-cadherin gene is associated with colorectal cancer. Carcinogenesis 2004;11(25): [18] Cattaneo F, Venesio T, Molatore S, et al. Functional Analysis and Case-control study of -160C/A polymorphism in the E-cadherin Gene promoter: Association with cancer risk. Anticancer Research 2006;26: [19] Nakamura A, Shimazaki T, Kaneko K, et al. Characterization of DNA polymorphisms in the E-cadherin gene (CDH1) promoter region. Mutation Research 2002;502: [20] Sutton AJ, Abrams KR, Jones DR, Sheldon TA, Song F: Methods for meta-analysis in medical research. John Wiley and Sons, New York, [21] Cochran WG: The combination of estimates from different experiments. Biometrics 1954;10: [22] Petitti DB. Approaches to heterogeneity in meta-analysis. Stat Med. 2001;20: [23] Higgins JP, Thompson SG, Deeks JJ, Altman DG. Measuring inconsistency in meta-analyses. BMJ 2003;327: [24] Lee JY. Medical Statistics at a Glance. Seoul, Epublic, [25] DerSimonian R, Laird N. Meta-analysis in clinical trials. Control Clin Trials. 1986;7: [26] Petitt DB. Meta-analysis, decision analysis, and cost-effectiveness analysis: methods for quantitative synthesis in medicine. 2nd ed. New York: Oxford University Press;2000. [27] Lee JY. Meta-analysis. J Korean Soc Endocrinol 2008;23(6): [28] Ahn BJ, Chun SI. Green tea consumption and stomach cancer risk in the Asian population: a meta-analysis ofpprospective studies. Korean J Health Promot Dis Prev 2009;9(3): [29] Borenstein M, Hedges L, Higgins J, et al. Comprehensive Meta-analysis Version 2. Engelwood NJ Biostat [30] Ahn YJ, Jang JY, Lee SE, Hwang DW, Song YS, Cho DY, Kim SW. Germline genetic alterations in intraductal papillary neopla associated with extrapancreatic tumors. J Korean Surg Soc 2009;76: [31] Yoon KA, Ku JL, Yang HK, Kim WH, Park SY, Park JG. Germline mutations of E-cadherin gene in Korean familial gastric cancer patients. J Hum Genet 1999;44:

15 CDH1-160C>A 15 [32] Li LC, Chui RM, Sasaki M, Nakajima K, Perinchery G, Au HC, et al. A single nucleotide polymorphism in the E-cadherin gene promoter alters transcriptional activities. Cancer Res 2000;60: [33] Park WS, Cho YG, Park JY, Kim CJ, Lee JH, Kim HS, et al. A single nucleotide polymorphism in the E-cadherin gene promoter-160 is not associated with risk of Korean gastric cancer. J Korean Med Sci 2003;18: [34] Zou XP, Dai WJ, Cao J. CDH1 promoter polymorphism (-347GGA) is a possible prognostic factor in sporadic colorectal cancer. World J Gastroenterol 2009;15(42): [35] Wheeler JM, Kim HC, Efstathiou JA, et al. Hypermethyaltion of the promoter region of the E-cadherin gene (CDH1) in sporadic and ulcerative colitis associated colorectal cancer. Gut 2001;48: [36] Li LC, Chui RM, Sasaki M, et al. A single nucleotide polymorphism in the E-cadherin gene promoter alters transcriptional activities. Cancer Res 2000;60: [37] Wang GY, Lu CQ, Zhang RM, et al. The E-cadherin gene polymorphism 160->A and cancer risk: a HuGE review and meta-analysis of 26 case-control studies. Am J Epidemiol 2008;167:7-14.

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Can032.hwp Chromosomal Alterations in Hepatocellular Carcinoma Cell Lines Detected by Comparative Genomic Hybridization Sang Jin Park 1, Mahn Joon Ha, Ph.D. 1, Hugh Chul Kim, M.D. 2 and Hyon Ju Kim, M.D. 1 1 Laboratory