정신분열병과 대장암 환자에서 APC 종양억제유전자의 유전자 다형성에 관한 연구
Diffenences in APC Gene Polymorphisms between Korean Patients with Schizophrenia and Colon Cancer
0
조회
0
다운로드
0
인용
0
참고문헌
초록
Objectives：Compared with the general population, low incidence of cancers in patients with schizophrenia has been observed. It has been proposed that genetic predisposition toward schizophrenia is associated with reduced vulnerability to cancer. Adenomatous polyposis coli(APC) genes, a tumor suppressor gene, is involved in colorectal tumorigenesis. In order to analyze the genetic difference between Korean schizophrenia and colon cancer patients,polymorphisms of APC gene were studied. Methods：Two hundred and forty eight schizophrenia patients, 248 colon cancer patients, and 248 control subjects were used to identify the SNPs. Genetic analysis was carried out in the rs2229992 and rs456899 SNP regions using the SNP-IT™ assay. The allele, genotype and haplotype frequencies were compared between the three groups. Results：The genotype, allele, and haplotype of the APC polymorphisms in schizophrenia patients were not significant different from those of controls. When compared colon cancer patients, the schizophrenia patients showed significantly more frequent in rs2229992 CT/TT genotype(odds ratio 2.179, 95% confidence interval(CI)=1.20-3.959)and the male schizophrenia patients revealed significant differences in T-G haplotype(odds ratio 2.5915, 95%CI=1.4677-4.5759), after adjusting for age and sex. Conclusion：These results suggest that the APC polymorphisms found in schizophrenia patients, especially in males, may be associated with reduced vulnerability to colon cancer.
Abstract
Objectives：Compared with the general population, low incidence of cancers in patients with schizophrenia has been observed. It has been proposed that genetic predisposition toward schizophrenia is associated with reduced vulnerability to cancer. Adenomatous polyposis coli(APC) genes, a tumor suppressor gene, is involved in colorectal tumorigenesis. In order to analyze the genetic difference between Korean schizophrenia and colon cancer patients,polymorphisms of APC gene were studied. Methods：Two hundred and forty eight schizophrenia patients, 248 colon cancer patients, and 248 control subjects were used to identify the SNPs. Genetic analysis was carried out in the rs2229992 and rs456899 SNP regions using the SNP-IT™ assay. The allele, genotype and haplotype frequencies were compared between the three groups. Results：The genotype, allele, and haplotype of the APC polymorphisms in schizophrenia patients were not significant different from those of controls. When compared colon cancer patients, the schizophrenia patients showed significantly more frequent in rs2229992 CT/TT genotype(odds ratio 2.179, 95% confidence interval(CI)=1.20-3.959)and the male schizophrenia patients revealed significant differences in T-G haplotype(odds ratio 2.5915, 95%CI=1.4677-4.5759), after adjusting for age and sex. Conclusion：These results suggest that the APC polymorphisms found in schizophrenia patients, especially in males, may be associated with reduced vulnerability to colon cancer.
참고문헌 (33)
- American Psychiatric Association, "Diagnostic and Statistical Mannual of Mental Disorders. 4th ed", pp.274~292 (1994), American Psychiatric Association
- Buchanan RW, "Schizophrenia. In Kaplan & Sadock’s Comprehensive Textbook of Psychiatry", pp.1096~1109 (2000), Lipponcott Williams & Wilkins
- McGuffin P, "Genetic basis of schizophrenia", Lancet, 346, pp.678~682 (1995)
- Tsuang MT, "The genetics of schizophrenia. Current knowledge and future directions", Schizophr Res, 4, pp.157~171 (1991)
- Gottesman, II, "A critical review of recent adoption, twin, and family studies of schizophrenia: behavioralgenetics perspectives", Schizophr Bull, 2, pp.360~401 (1976)
- Kety SS, "Mental illness in the biological and adoptive families of adopted individuals who have become schizophrenic: a preliminary report based on psychiatric interviews", Proc Annu Meet Am Psychopathol Assoc, 63, pp.147~165 (1975)
- Catts VS, "Apoptosis and schizophrenia: is the tumour suppressor gene, p53, a candidate susceptibility gene?", Schizophr Res, 41, pp.405~415 (2000)
- Cohen M, "The association between schizophrenia and cancer: a population-based mortality study", Schizophr Res, 57, pp.139~146 (2002)
- Mortensen PB, "The incidence of cancer in schizophrenic patients", J Epidemiol Community Health, 43, pp.43~47 (1989)
- Goldman LS, "Medical illness in patients with schizophenia", J Clin Psychiatry, 60, pp.10~15 (1999)
- Mortensen PB, "The occurrence of the first admitted schizophrenic patients", Schizophr Res, 12, pp.185~194 (1994)
- Lichtermann D, "Incidence of cancer among patients with schizophrenia and their relatives", Arch Gen Psychiatry, 58, pp.573~578 (2001)
- Levav I, "Cancer risk among parents and sibling of patients with schizophrenia", Br J Psychiatry, 190, pp.156~161 (2007)
- Park JK, "Differences in p53 gene polymorphisms between Korean schizophrenia and lung cancer patients", Schizophr Res, 67, pp.71~74 (2004)
- Yang Y, "Tumor suppressor gene TP53 is genetically associatedwith schizophrenia in the Chinese population", Neurosci Lett, 369, pp.126~131 (2004)
- Lim YJ, "Epidermal growth factor gene polymorphism is different between schizophrenia and lung cancer patients in the Korean population", Neurosci Lett, 374, pp.157~160 (2005)
- Powell SM, "Thibodeau SN, et al. APC mutations occur early during colorectal tumorigenesis", Nature, 17, pp.235~237 (1992)
- Groden J, "Mutational analysis of patients with adenomatous polyposis: identical inactivating mutations in unrelated individuals", Am J Hum Genet, 52, pp.263~272 (1993)
- Groden J, "Identification and characterization of the familial adenomatous polyposis coli gene", Cell, 66, pp.589~600 (1991)
- Usadel H, "Quantitative adenomatous polyposis coli promoter methylation analysis in tumor tissue, serum, and plasma DNA of patients with lung cancer", Cancer Res, 62, pp.371~375 (2002)
- Gerstein AV, "APC", CTNNB1(beta-catenin) pathway alterations in human prostate cancers, 2002, pp.34, 9~16
- Akiyama T, "Wnt", beta-catenin signaling, 2000, pp.11, 273~282
- Cotter D, "Abnormalities of Wnt signaling in schizophrenia--evidence for neurodevelopmental abnormality", Neuroreport, 9, pp.1379~1383 (1998)
- Cui DH, "The tumor suppressor adenomatous coli gene is associated with susceptibility to schizophrenia", Mol Psychiatry, 10, pp.669~677 (2005)
- Hanson CA, "Non-traditional roles for the Adenomatous Polyposis Coli(APC) tumor suppressor protein", Gene, 361, pp.1~12 (2005)
- Straub RE, "Support for a possible schizophrenia vulnerability locus in region 5q22-31 in Irish families", Mol Psychiatry, 2, pp.148~155 (1997)
- Mirnics K, "Analysis of complex brain disorders with gene expression microarrays: schizophrenia as a disease of the synapse", Trends Neurosci, 24, pp.479~486 (2001)
- Fernandez E, "Sex differences in colorectal cancer mortality in Europe, 1955-1996", Eur J Cancer Prev, 9, pp.99~104 (2000)
- Allam MF, "Aetiology of sex differences in colorectal cancer", Eur J Cancer Prev, 10, pp.299~300 (2001)
- Aleman A, "Sex differences in the risk of schizophrenia: Evidence from meta-analysis", Arch Gen Psychiatry, 60, pp.565~571 (2003)
- McGrath JJ, "Variations in the incidence of schizophrenia: Data versus Dogma", Schizophr Bull, 32, pp.195~197 (2006)
- Saku M, "Mortality in psychiatric patients, with a specific focus on cancer mortality associated with schizophrenia", Int J Epidemiol, 24, pp.366~372 (1995)
- Dalton SO, "Risk for cancer in cohort of patients hospitalized for schizophrenia in Denmark, 1969-1993", Schizophr Res, 75, pp.315~324 (2005)