Top

International Journal of Colorectal Disease

Published in:

01-10-2007 | Original Article

Germline mutations of the MYH gene in Korean patients with multiple colorectal adenomas

Authors: Duck-Woo Kim, Il-Jin Kim, Hio-Chung Kang, Sang-Geun Jang, Kun Kim, Hyun-Ju Yoon, Sun-A Ahn, Song Yee Han, Seung-Hyun Hong, Jung-A Hwang, Dae Kyung Sohn, Seung-Yong Jeong, Hyo Seong Choi, Chang Won Hong, Seok-Byung Lim, Jae-Gahb Park

Published in: International Journal of Colorectal Disease | Issue 10/2007

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.

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 30:227–232PubMedCrossRef

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 119:807–814PubMedCrossRef

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 96:1631–1634PubMedCrossRef

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 77:112–119PubMedCrossRef

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 49:272–275PubMedCrossRef

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 109:680–684PubMedCrossRef

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 15:312–314CrossRef

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 11:2961–2967PubMedCrossRef

Kim DW, Kim IJ, Kang HJ et al (2005) Mutation spectrum of the APC gene in 83 Korean FAP families. Human Mutat 26:281CrossRef

10.

Kim H, Kim HJ, Chi SG (2006) Absence of MutY homologue mutation in patients with multiple sporadic adenomatous polyps in Korea. World J Gastroenterol 12:951–955PubMed

11.

Leite JS, Isidro G, Martins M et al (2005) Is prophylactic colectomy indicated in patients with MYH-associated polyposis? Colorectal Dis 7:327–331PubMedCrossRef

12.

Lipton L, Halford SE, Johnson V et al (2003) Carcinogenesis in MYH-associated polyposis follows a distinct genetic pathway. Cancer Res 63:7595–7599PubMed

13.

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 174:6321–6325PubMed

14.

Miyaki M, Iijima T, Yamaguchi T et al (2005) Germline mutations of the MYH gene in Japanese patients with multiple colorectal adenomas. Mutat Res 578:430–433PubMed

15.

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:e54PubMedCrossRef

16.

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 94:8016–8020PubMedCrossRef

17.

Russell AM, Zhang J, Luz J et al (2006) Prevalence of MYH germline mutations in Swiss APC mutation-negative polyposis patients. Int J Cancer 118:1937–1940PubMedCrossRef

18.

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 268:23524–23530PubMed

19.

Sampson JR, Dolwani S, Jones S et al (2003) Autosomal recessive colorectal adenomatous polyposis due to inherited mutations of MYH. Lancet 362:39–41PubMedCrossRef

20.

Shibutani S, Takeshita M, Grollman AP (1991) Insertion of specific bases during DNA synthesis past the oxidation-damaged base 8-oxodG. Nature 349:431–434PubMedCrossRef

21.

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 348:791–799PubMedCrossRef

22.

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 178:3885–3892PubMed

23.

Sobin LH, Wittenkind CH (eds) (2002) International Union Against Cancer. TNM classification of malignant tumors, 6th edn. Wiley, New York

24.

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 25:1859–1866PubMedCrossRef

25.

Tenesa A, Campbell H, Barnetson R, Porteous M, Dunlop M, Farrington SM (2006) Association of MUTYH and colorectal cancer. Br J Cancer 95:239–242PubMedCrossRef

26.

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 126:1681–1685PubMedCrossRef

27.

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 127:9–16PubMedCrossRef

28.

Won YJ, Park KJ, Kwon HJ et al (1999) Germline mutations of the APC gene in Korean familial adenomatous polyposis patients. J Hum Genet 44:103–108PubMedCrossRef

Title: Germline mutations of the MYH gene in Korean patients with multiple colorectal adenomas
Authors: Duck-Woo Kim
Il-Jin Kim
Hio-Chung Kang
Sang-Geun Jang
Kun Kim
Hyun-Ju Yoon
Sun-A Ahn
Song Yee Han
Seung-Hyun Hong
Jung-A Hwang
Dae Kyung Sohn
Seung-Yong Jeong
Hyo Seong Choi
Chang Won Hong
Seok-Byung Lim
Jae-Gahb Park
Publication date: 01-10-2007
Publisher: Springer-Verlag
Published in: International Journal of Colorectal Disease / Issue 10/2007
Print ISSN: 0179-1958
Electronic ISSN: 1432-1262
DOI: https://doi.org/10.1007/s00384-007-0289-8

At a glance: The ONWARDS insulin icodec trials

Springer Medicine

Germline mutations of the MYH gene in Korean patients with multiple colorectal adenomas

Abstract

Background

Materials and methods

Results

Conclusion

At a glance: The ONWARDS insulin icodec trials

Springer Medicine

Abstract

Background

Materials and methods

Results

Conclusion

Please log in to get access to this content

Other articles of this Issue 10/2007

Ile105Val GSTP1 polymorphism and susceptibility to colorectal carcinoma in Bulgarian population

Letter to the editor concerning “HPV in anal squamous cell carcinoma and anal intraepithelial neoplasia (AIN)” by Varnai et al. (Int J Colorectal Dis 21:135–142, 2006)

Microsomal glutathione S-transferase gene polymorphisms and colorectal cancer risk in a Han Chinese population

Pseudomembranous colitis presenting as an isolated colonic stricture

Influence of the neo-adjuvant radiochemotherapy as a factor in the surgical treatment of rectal cancer by expert surgeon. A comparative study

Hsp70 response to 5-fluorouracil treatment in human colon cancer cell lines