Abstract
MYH, OGG1 and MTH1 are members of base excision repair (BER) families, and MYH germline mutations were recently identified in patients with multiple adenomas or familial adenomatous polyposis (FAP). A total of 20 APC-negative Korean FAP patients were analyzed for OGG1, MYH and MTH1 germline mutations. A total of 19 hereditary nonpolyposis colorectal cancer (HNPCC), 86 suspected HNPCC, and 246 sporadic colorectal cancer cases were investigated for OGG1 and MYH mutations. A total of 14 R154H OGG1 polymorphisms were identified in hereditary, sporadic colorectal cancers, and normal controls. For the case-control analysis of OGG1 R154H, a total of 625 hereditary or sporadic colorectal cancer patients and 527 normal controls were screened. R154H was a rare polymorphism associated with sporadic colorectal cancer patents (OR: 3.586, P= 0.053). R154H does not segregate with cancer phenotypes. Upon examining the possibility of recessive inheritance of R154H, we could not identify any complementary mutations in OGG1, MYH or MTH1. Samples with R154H were further screened for mutations of K-ras, β-catenin, APC, p53, BRAF and the microsatellite instability (MSI) status. Eight somatic mutations were identified in these genes and G:C to T:A transversion mutations were not dominant in samples harboring R154H. This result raises the possibility that OGG1 R154H may function as a low/moderate-penetrance modifier for colorectal cancer development.
This is a preview of subscription content, log in via an institution to check access.
Similar content being viewed by others
References
Al-Tassan N, Chmiel NH, Maynard J, Fleming N, Livingston AL, Williams GT, Hodges AK, Davies DR, David SS, Sampson JR, Cheadle JP (2002) Inherited variants of MYH associated with somatic G:C→T:A mutations in colorectal tumors. Nat Genet 30:227–232
Audebert M, Radicella JP, Dizdaroglu M (2000a) Effect of single mutations in the OGG1 gene found in human tumors on the substrate specificity of the Ogg1 protein. Nucleic Acids Res 28:2672–2678
Audebert M, Chevillard S, Levalois C, Gyapay G, Vieillefond A, Klijanienko J, Vielh P, El Naggar AK, Oudard S, Boiteux S, Radicella JP (2000b) Alterations of the DNA repair gene OGG1 in human clear cell carcinomas of the kidney. Cancer Res 60:4740- 4744
Bruner SD, Norman DP, Verdine GL (2000) Structural basis for recognition and repair of the endogenous mutagen 8-oxoguanine in DNA. Nature 403:859–866
Chevillard S, Radicella JP, Levalois C, Lebeau J, Poupon MF, Oudard S, Dutrillaux B, Boiteux S (1998) Mutations in OGG1, a gene involved in the repair of oxidative DNA damage, are found in human lung and kidney tumours. Oncogene 16:3083–3086
Halford SE, Rowan AJ, Lipton L, Sieber OM, Pack K, Thomas HJ, Hodgson SV, Bodmer WF, Tomlinson IP (2003) Germline mutations but not somatic changes at the MYH locus contribute to the pathogenesis of unselected colorectal cancers. Am J Pathol 162:1545–1548
Hyun JW, Choi JY, Zeng HH, Lee YS, Kim HS, Yoon SH, Chung MH (2000) Leukemic cell line, KG-1 has a functional loss of hOGG1 enzyme due to a point mutation and 8-hydroxydeoxyguanosine can kill KG-1. Oncogene 19:4476–4479
Jones S, Emmerson P, Maynard J, Best JM, Jordan S, Williams GT, Sampson JR, Cheadle JP (2002) Biallelic germline mutations in MYH predispose to multiple colorectal adenoma and somatic G:C→T:A mutations. Hum Mol Genet 11:2961–2967
Kim IJ, Ku JL, Yoon KA, Heo SC, Jeong SY, Choi HS, Hong KH, Yang SK, Park JG (2000) Germline mutations of the dpc4 gene in Korean juvenile polyposis patients. Int J Cancer 86:529–532
Kim IJ, Kang HC, Park JH, Ku JL, Lee JS, Kwon HJ, Yoon KA, Heo SC, Yang HY, Cho BY, Kim SY, Oh SK, Youn YK, Park DJ, Lee MS, Lee KW, Park JG (2002) RET oligonucleotide microarray for the detection of RET mutations in multiple endocrine neoplasia type 2 syndromes. Clin Cancer Res 8:457–463
Kim IJ, Shin Y, Kang HC, Park JH, Ku JL, Park HW, Park HR, Lim SB, Jeong SY, Kim WH, Park JG (2003a) Robust microsatellite instability (MSI) analysis by denaturing high-performance liquid chromatography (DHPLC). J Hum Genet 48:525–530
Kim IJ, Kang HC, Park JH, Shin Y, Ku JL, Lim SB, Park SY, Jung SY, Kim HK, Park JG (2003b) Development and applications of a beta-catenin oligonucleotide microarray: beta-catenin mutations are dominantly found in the proximal colon cancers with microsatellite instability. Clin Cancer Res 9:2920–2925
Kim IJ, Park JH, Kang HC, Shin Y, Lim SB, Ku JL, Yang HK, Lee KU, Park JG (2003c) A novel germline mutation in the MET extracellular domain in a Korean patient with the diffuse type of familial gastric cancer. J Med Genet 40:e97
Kim IJ, Park JH, Kang HC, Shin Y, Park HW, Park HR, Ku JL, Lim SB, Park JG (2003d) Mutational analysis of BRAF and K-ras in gastric cancers: Absence of BRAF mutations in gastric cancers. Hum Genet 114:118–120
Kim IJ, Kang HC, Park JH, Shin Y, Ku JL, Yoo BC, Park JG (2003e) Development and application of an oligonucleotide microarray for mutational analysis. In: Hardiman G (ed) Microarrays methods and applications. DNA Press, Pennsylvania, pp 250–271
Laken SJ, Papadopoulos N, Petersen GM, Gruber SB, Hamilton SR, Giardiello FM, Brensinger JD, Vogelstein B, Kinzler KW (1999) Analysis of masked mutations in familial adenomatous polyposis. Proc Natl Acad Sci USA 96:2322–2326
Park JG, Vasen HF, Park YJ, Park KJ, Peltomaki P, de Leon MP, Rodriguez-Bigas MA, Lubinski J, Beck NE, Bisgaard ML, Miyaki M, Wijnen JT, Baba S, Lindblom A, Madlensky L, Lynch HT (2002) Suspected HNPCC and Amsterdam criteria II: evaluation of mutation detection rate, an international collaborative study. Int J Colorectal Dis 17:109–114
Park JH, Kim IJ, Kang HC, Shin Y, Park HW, Jang SG, Ku JL, Lim SB, Jeong SY, Park JG (2004) Oligonucleotide microarray-based mutation detection of the K-ras gene in colorectal cancers using competitive DNA hybridization (CDH). Clin Chem 50:1688–1691
Park YJ, Choi EY, Choi JY, Park JG, You HJ, Chung MH (2001) Genetic changes of hOGG1 and the activity of oh8Gua glycosylase in colon cancer. Eur J Cancer 37:340–346
Sampson JR, Dolwani S, Jones S, Eccles D, Ellis A, Evans DG, Frayling I, Jordan S, Maher ER, Mak T, Maynard J, Pigatto F, Shaw J, Cheadle JP (2003) Autosomal recessive colorectal adenomatous polyposis due to inherited mutations of MYH. Lancet 362:39–41
Shin KH, Park YJ, Park JG (2000) Mutational analysis of the transforming growth factor beta receptor type II gene in hereditary nonpolyposis colorectal cancer and early-onset colorectal cancer patients. Clin Cancer Res 6:536–540
Shinmura K, Kohno T, Kasai H, Koda K, Sugimura H, Yokota J (1998) Infrequent mutations of the hOGG1 gene, that is involved in the excision of 8-hydroxyguanine in damaged DNA, in human gastric cancer. Jpn J Cancer Res 89:825–828
Sidransky D, Von Eschenbach A, Tsai YC, Jones P, Summerhayes I, Marshall F, Paul M, Green P, Hamilton SR, Frost P et al (1991) Identification of p53 gene mutations in bladder cancers and urine samples. Science 252:706–709
Sieber OM, Lipton L, Crabtree M, Heinimann K, Fidalgo P, Phillips RK, Bisgaard ML, Orntoft TF, Aaltonen LA, Hodgson SV, Thomas HJ, Tomlinson IP (2003) Multiple colorectal adenomas, classic adenomatous polyposis, and germ-line mutations in MYH. N Engl J Med 348:791–799
Won YJ, Park KJ, Kwon HJ, Lee JH, Kim JH, Kim YJ, Chun SH, Han HJ, Park JG (1999) Germline mutations of the APC gene in Korean familial adenomatous polyposis patients. J Hum Genet 44:103–108
Acknowledgements
This work was supported by a research grant from the National Cancer Center, Korea and the BK21 project for Medicine, Dentistry and Pharmacy.
Author information
Authors and Affiliations
Corresponding author
Additional information
I.-J. Kim and J.-L. Ku contributed equally to this work
Rights and permissions
About this article
Cite this article
Kim, IJ.., Ku, JL., Kang, H.C. et al. Mutational analysis of OGG1, MYH, MTH1 in FAP, HNPCC and sporadic colorectal cancer patients: R154H OGG1 polymorphism is associated with sporadic colorectal cancer patients. Hum Genet 115, 498–503 (2004). https://doi.org/10.1007/s00439-004-1186-7
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s00439-004-1186-7