Abstract
Background
Most investigations on MutY human homolog (MYH)-associated polyposis (MAP) have been conducted in Western countries. Limited data on MAP in Asia are currently available. The present study investigated germline mutations of the MYH gene among patients with 10 to 99 adenomatous colorectal polyps and familial adenomatous polyposis (FAP) without adenomatous polyposis coli (APC) germline mutations in Korea.
Materials and methods
The study population included 46 patients with 10 to 99 adenomatous polyps in the colorectum and 16 FAP patients with no identified APC germline mutations. Subjects were screened for MYH germline mutations, and we additionally screened for MYH mutations in 96 normal control individuals.
Results
Two of 46 (4.3%) patients with multiple polyps displayed heterozygous biallelic germline mutations of the MYH gene. A 39-year-old male patient with biallelic MYH mutations (p.G272E and p.A359V) received total proctocolectomy for rectal cancer and 36 colorectal polyps. A 58-year-old female patient with biallelic MYH mutations (p.Q253X and p.Q440P) received right hemicolectomy for ascending colon cancer and 16 colonic polyps. The frequency of biallelic MYH mutation in 14 of 46 multiple-polyp patients, who had 15 to 99 polyps, was 14.3% (2 of 14). No biallelic MYH mutations were detected in the 32 patients with 10 to 14 colorectal polyps, 16 FAP patients, or 96 normal controls.
Conclusion
We identified biallelic MYH germline mutations in 2 of 14 (14.3%) Korean patients with 15 to 99 colorectal polyps. In this study, there was no Y165C or G382D hot-spot mutation, which had been reported most frequently in previous studies.
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 et al (2002) Inherited variants of MYH associated with somatic G:C→T:A mutations in colorectal tumors. Nat Genet 30:227–232
Aretz S, Uhlhaas S, Goergens H et al (2006) MUTYH-associated polyposis: 70 of 71 patients with biallelic mutations present with an attenuated or atypical phenotype. Int J Cancer 119:807–814
Croitoru ME, Cleary SP, Di Nicola N et al (2004) Association between biallelic and monoallelic germline MYH gene mutations and colorectal cancer risk. J Natl Cancer Inst 96:1631–1634
Farrington SM, Tenesa A, Barnetson R et al (2005) Germline susceptibility to colorectal cancer due to base-excision repair gene defects. Am J Hum Genet 77:112–119
Fornasarig M, Minisini AM, Viel A, Quaia M, Canzonieri V, Veronesi A (2006) Twelve years of endoscopic surveillance in a family carrying biallelic Y165C MYH defect: report of a case. Dis Colon Rectum 49:272–275
Gismondi V, Meta M, Bonelli L et al (2004) Prevalence of the Y165C, G382D and 1395delGGA germline mutations of the MYH gene in Italian patients with adenomatous polyposis coli and colorectal adenomas. Int J Cancer 109:680–684
Jenkins MA, Croitoru ME, Monga N et al (2006) Risk of colorectal cancer in monoallelic and biallelic carriers of MYH mutations: a population-based case-family study. Cancer Epidemiol Biomark Prev 15:312–314
Jones S, Emmerson P, Maynard J et al (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 DW, Kim IJ, Kang HJ et al (2005) Mutation spectrum of the APC gene in 83 Korean FAP families. Human Mutat 26:281
Kim H, Kim HJ, Chi SG (2006) Absence of MutY homologue mutation in patients with multiple sporadic adenomatous polyps in Korea. World J Gastroenterol 12:951–955
Leite JS, Isidro G, Martins M et al (2005) Is prophylactic colectomy indicated in patients with MYH-associated polyposis? Colorectal Dis 7:327–331
Lipton L, Halford SE, Johnson V et al (2003) Carcinogenesis in MYH-associated polyposis follows a distinct genetic pathway. Cancer Res 63:7595–7599
Michaels ML, Miller JH (1992) The G0 system protects organisms from the mutagenic effect of the spontaneous lesion 8-hydroxyguanine (7,8-dihydro-8-oxoguanine). J Bacteriol 174:6321–6325
Miyaki M, Iijima T, Yamaguchi T et al (2005) Germline mutations of the MYH gene in Japanese patients with multiple colorectal adenomas. Mutat Res 578:430–433
Nielsen M, Franken PF, Reinards TH et al (2005) Multiplicity in polyp count and extracolonic manifestations in 40 Dutch patients with MYH associated polyposis coli (MAP). J Med Genet 42:e54
Roldan-Arjona T, Wei YF, Carter KC et al (1997) Molecular cloning and functional expression of a human cDNA encoding the antimutator enzyme 8-hydroxyguanine-DNA glycosylase. Proc Natl Acad Sci USA 94:8016–8020
Russell AM, Zhang J, Luz J et al (2006) Prevalence of MYH germline mutations in Swiss APC mutation-negative polyposis patients. Int J Cancer 118:1937–1940
Sakumi K, Furuichi M, Tsuzuki T et al (1993) Cloning and expression of cDNA for a human enzyme that hydrolyzes 8-oxo-dGTP, a mutagenic substrate for DNA synthesis. J Biol Chem 268:23524–23530
Sampson JR, Dolwani S, Jones S et al (2003) Autosomal recessive colorectal adenomatous polyposis due to inherited mutations of MYH. Lancet 362:39–41
Shibutani S, Takeshita M, Grollman AP (1991) Insertion of specific bases during DNA synthesis past the oxidation-damaged base 8-oxodG. Nature 349:431–434
Sieber OM, Lipton L, Crabtree M et al (2003) Multiple colorectal adenomas, classic adenomatous polyposis, and germ-line mutations in MYH. N Engl J Med 348:791–799
Slupska MM, Baikalov C, Luther WM, Chiang JH, Wei YF, Miller JH (1996) Cloning and sequencing a human homolog (hMYH) of the Escherichia coli mutY gene whose function is required for the repair of oxidative DNA damage. J Bacteriol 178:3885–3892
Sobin LH, Wittenkind CH (eds) (2002) International Union Against Cancer. TNM classification of malignant tumors, 6th edn. Wiley, New York
Tao H, Shinmura K, Hanaoka T et al (2004) A novel splice-site variant of the base excision repair gene MYH is associated with production of an aberrant mRNA transcript encoding a truncated MYH protein not localized in the nucleus. Carcinogenesis 25:1859–1866
Tenesa A, Campbell H, Barnetson R, Porteous M, Dunlop M, Farrington SM (2006) Association of MUTYH and colorectal cancer. Br J Cancer 95:239–242
Venesio T, Molatore S, Cattaneo F, Arrigoni A, Risio M, Ranzani GN (2004) High frequency of MYH gene mutations in a subset of patients with familial adenomatous polyposis. Gastroenterology 126:1681–1685
Wang L, Baudhuin LM, Boardman LA et al (2004) MYH mutations in patients with attenuated and classic polyposis and with young-onset colorectal cancer without polyps. Gastroenterology 127:9–16
Won YJ, Park KJ, Kwon HJ et al (1999) Germline mutations of the APC gene in Korean familial adenomatous polyposis patients. J Hum Genet 44:103–108
Acknowledgment
D-W Kim and I-J Kim equally contributed to this work.
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Kim, DW., Kim, IJ., Kang, HC. et al. Germline mutations of the MYH gene in Korean patients with multiple colorectal adenomas. Int J Colorectal Dis 22, 1173–1178 (2007). https://doi.org/10.1007/s00384-007-0289-8
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s00384-007-0289-8